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| Name (Synonyms) | Correlation | |
|---|---|---|
| drug1751 | GSK3640254 Wiki | 0.42 |
| drug887 | Cabotegravir Tablets Wiki | 0.34 |
| drug3699 | Rilpivirine Tablets Wiki | 0.34 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug638 | Blood Sample Wiki | 0.24 |
| drug1752 | GSK3640254 200 mg Wiki | 0.24 |
| drug1356 | Dolutegravir Wiki | 0.24 |
| drug3354 | Pravastatin 40 mg Wiki | 0.24 |
| drug2672 | Montelukast 10 mg Wiki | 0.24 |
| drug1690 | Flurbiprofen 100 mg Wiki | 0.24 |
| drug511 | BIKTARVY Tablets (BIK) Wiki | 0.24 |
| drug25 | 10% Povidone-iodine nasal decolonization swab plus 0.12% CHG oral rinse Wiki | 0.24 |
| drug1624 | FTC/TAF Wiki | 0.24 |
| drug1548 | Etravirine (ETR) Wiki | 0.24 |
| drug3817 | SKILLZ-Girl Enhanced football curriculum Wiki | 0.24 |
| drug2616 | Midazolam 5 mg (2.5 mL) Wiki | 0.24 |
| drug23 | 1. Characterize the immune response after infection with SARS-CoV-2 Wiki | 0.24 |
| drug886 | Cabotegravir Injectable Suspension (CAB LA) Wiki | 0.24 |
| drug889 | Cabotegravir sodium (Oral Lead In) Wiki | 0.24 |
| drug1754 | GSK3739937 Wiki | 0.24 |
| drug1753 | GSK3640254 Oral tablet Wiki | 0.24 |
| drug1735 | GLA-SE adjuvant Wiki | 0.24 |
| drug1256 | Darunavir/Ritonavir (DRV/RTV) Wiki | 0.24 |
| drug2944 | Omeprazole 40 mg Wiki | 0.24 |
| drug2610 | Metoprolol 100 mg Wiki | 0.24 |
| drug1333 | Digoxin 0.25 mg Wiki | 0.24 |
| drug755 | CH505TF gp120 Wiki | 0.24 |
| drug4798 | [14C]-GSK3640254 intravenous infusion Wiki | 0.24 |
| drug3700 | Rilpivirine extended release suspension for injection (long-acting) Wiki | 0.24 |
| drug4799 | [14C]-GSK3640254 powder Wiki | 0.24 |
| drug87 | ABC/3TC Wiki | 0.24 |
| drug884 | Cabotegravir 200 mg/mL Wiki | 0.24 |
| drug888 | Cabotegravir extended release suspension for injection (long-acting) Wiki | 0.24 |
| drug890 | Caffeine 200 mg Wiki | 0.24 |
| drug3698 | Rilpivirine Injectable Suspension (RPV LA) Wiki | 0.24 |
| drug885 | Cabotegravir 400 mg/mL Wiki | 0.24 |
| drug12 | 0.9% (w/v) saline Wiki | 0.24 |
| drug4268 | TERA Intervention Wiki | 0.24 |
| drug3943 | Serology test for COVID-19 Wiki | 0.17 |
| drug2683 | Moxifloxacin Wiki | 0.17 |
| drug14 | 0.9% Saline Wiki | 0.17 |
| drug171 | AZD1222 Wiki | 0.14 |
| drug5169 | questionnaire Wiki | 0.08 |
| drug297 | Anakinra Wiki | 0.07 |
| drug2827 | No intervention Wiki | 0.05 |
| drug3195 | Placebo Wiki | 0.04 |
| drug4102 | Standard of Care Wiki | 0.04 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| D000163 | Acquired Immunodeficiency Syndrome NIH | 0.49 |
| D007239 | Infection NIH | 0.03 |
| D003141 | Communicable Diseases NIH | 0.02 |
| Name (Synonyms) | Correlation |
|---|
Navigate: Correlations HPO
There are 17 clinical trials
Youth Living with HIV (YLWH) often face unique challenges achieving high and sustained rates of adherence to their antiretroviral therapy (ART). Poor adherence can lead to unsuppressed virus, more advanced HIV disease and poorer health outcomes, eventually exhausting treatment options. To date however, there are few demonstrated interventions for youth failing first line therapy. This study will evaluate a novel intervention that uses remote coaching through video enabled counseling sessions, a 'smart' pill bottle that notifies an adherence coach when youth fail to open/close the device around dose time, and problem solving outreach by the coach when and as needed. This intensive 'boot camp' strategy is implemented for 12 weeks followed by observation through 48 weeks.
Description: Participants with HIV-1 RNA < 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA >= 50 copies/ml or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
Measure: Proportion of participants with plasma Human Immunodeficiency Virus - Type I ribonucleic acid (HIV-1 RNA) levels less than (<) 50 copies/mL at week 12 Time: 12 weeks post enrollmentDescription: Participants with HIV-1 RNA < 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA >= 200 copies/ml or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
Measure: Proportion of participants with HIV-1 RNA < 200 copies/mL at week 12 Time: 12 weeks post enrollmentDescription: Participants with HIV-1 RNA < 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA >= 50 copies/ml or with no HIV-1 RNA measurement within the week window are classified as failures.
Measure: Proportion of participants with HIV-1 RNA < 50 copies/mL at weeks 24, 36 and 48 Time: 24, 36 and 48 weeks post enrollmentDescription: Participants with HIV-1 RNA < 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA >= 200 copies/ml or with no HIV-1 RNA measurement within the week window are classified as failures.
Measure: Proportion of participants with HIV-1 RNA < 200 copies/mL at weeks 24, 36 and 48 Time: 24, 36 and 48 weeks post enrollmentDescription: Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are < 200 copies/ml and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is < 200 copies/ml. Otherwise the participant is classified as a failure.
Measure: Proportion of participants with HIV-1 RNA < 200 copies/mL at 12 weeks and maintained through 48 weeks Time: 24, 36 and 48 weeks post enrollmentDescription: For each participant, the percentage of days in each 7-day period in which all doses were taken is calculated, and then averaged across the 12 week interval (or number of weeks with available data).
Measure: Percent of days with all doses taken per week from weeks 0-12, 12-24, 24-36 and 36-48 Time: Enrollment through 48 weeksDescription: For each participant, the percentage of days in each 7-day period in which all doses were taken within the defined acceptable windows (within 4 hours for once/day ART and within 2 hours for twice/day ART) is calculated, and then averaged across the 12 week interval (or number of weeks with available data).
Measure: Percent of days with all doses taken within defined acceptable windows (within 4 hours for once/day ART and within 2 hours for twice/day ART) per week from weeks 0-12, 12-24, 24-36 and 36-48 Time: Enrollment through 48 weeksDescription: For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of gaps between doses of >7 consecutive days relative to the number of days with data reported, times 100. Consecutive gaps of more than 7 days increase the gap count by one, e.g. missing 20 days counts as 2 gaps.
Measure: Incidence rate (per 100 days) of gaps between dosing of at least 7 consecutive days between weeks 0-12, 12-24, 24-36 and 36-48 Time: Enrollment through 48 weeksCurrently, limited data is available about patients with HIV in the context of the COVID-19 pandemic. People with HIV who have not achieved viral suppression through antiretroviral treatment may have a compromised immune system that leaves them vulnerable to infections and disease progression. However, little is known about the presentation and clinical outcomes of patients with HIV and SARS-CoV-2. Our aim is to characterize the clinical presentation and disease course of COVID-19 in patients with HIV.
Description: COVID-19 related death among patients with HIV and COVID-19
Measure: Mortality Time: 30 daysDescription: Percentage of patients who required hospitalization
Measure: Frequency of patients requiring hospital admissions Time: 30 daysDescription: Percentage of patients who required ICU admission
Measure: Frequency of patients requiring ICU admissions Time: 30 daysDescription: Percentage of patients who required respiratory support (new oxygen use, non-invasive ventilation,or invasive ventilation)
Measure: Frequency of respiratory support use Time: 30 daysDescription: Percentage of patients who developed acute kidney injury defined as increase in baseline creatinine, or use of renal replacement therapy
Measure: Frequency of kidney injury Time: 30 daysDescription: Percentage of patients who developed liver injury defined as increase in baseline ALT
Measure: Frequency of liver injury Time: 30 daysThis is a phase 1, open label study in healthy participants to assess the pharmacokinetics of cabotegravir and rilpivirine in plasma following the administration of a single 600 milligram (mg) and a 900 mg intramuscular (IM) injection respectively, to separate vastus lateralis muscles on each leg. Cabotegravir is an integrase inhibitor being developed in combination with rilpivirine, a non-nucleoside reverse transcriptase inhibitor, for the treatment of human immunodeficiency virus (HIV). The objective is to evaluate pharmacokinetics, tolerability, and safety of cabotegravir long acting plus rilpivirine long acting administered concomitantly as two separate IM injections in the vastus lateralis muscle of adult healthy participants. The screening phase will be of 30 days, oral lead-in (OLI) phase of 28 days, there will be washout period of 10-14 days, followed by an injection phase and follow-up period will be up to 52-weeks. Approximately 15 adult healthy participants will be enrolled.
Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Maximum observed concentration (Cmax) for cabotegravir (injection phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Time of Cmax (Tmax) for cabotegravir (injection phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for cabotegravir (injection+follow-up phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for cabotegravir (injection+follow-up phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Apparent terminal phase half-life (t1/2) for cabotegravir (follow-up phase) Time: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Absorption rate constant for cabotegravir (follow-up phase) Time: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
Measure: Cmax for rilpivirine (injection phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
Measure: Tmax for rilpivirine (injection phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
Measure: AUC(0-t) for rilpivirine (injection+follow-up phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
Measure: AUC(0-infinity) for rilpivirine (injection+follow-up phase) Time: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
Measure: t1/2 for rilpivirine (follow-up phase) Time: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
Measure: Absorption rate constant for rilpivirine (follow-up phase) Time: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52COHIVE is an observational cohort nested in four antiretroviral therapy research studies (ADVANCE - NCT03122262; D²EFT - NCT03017872; DolPHIN2 - NCT03249181 and NAMSAL-ANRS12313 - NCT02777229). COHIVE will include participants who are possible COVID-19 cases with symptoms or confirmed COVID-19 cases, and participants who agree to have a serology testing for SARS-CoV-2 regardless of COVID-19 history.
Description: To characterise the clinical features of symptomatic COVID-19 in PLWH (cardio-respiratory and other clinical signs or symptoms), described overall and by HIV and comorbid disease factors including pregnancy status.
Measure: Clinical features of symptomatic COVID-19 in people living with HIV (PLWH) Time: At baselineDescription: To characterise the clinical outcomes of symptomatic COVID-19 in PLWH, assessing the outcomes of patients including the percentage of patients who are fully recovered, required hospitalisation, developed severe illness (ICU admission or equivalent) or died.
Measure: Clinical outcomes of symptomatic COVID-19 in PLWH Time: At Day 28Description: To characterise the clinical outcomes of symptomatic COVID-19 in PLWH, assessing the outcomes of patients including the percentage of patients who are fully recovered, required hospitalisation, developed severe illness (ICU admission or equivalent) or died.
Measure: Clinical outcomes of symptomatic COVID-19 in PLWH Time: At Month 3Description: To determine seroprevalence of COVID-19 in all parent study participants regardless of COVID-19 history.
Measure: Seroprevalence of COVID-19 in all parent study participants Time: Through study completion, an average of one yearThis is an open-label, single sequence study that is being conducted to investigate the potential drug-drug interaction (DDI) when GSK3640254 is co-administered with a cocktail of cytochrome P450 (CYP) enzymes and transporter probe substrates in healthy participants. This study will aid in understanding these interactions and resulting changes in exposure (if any) when drugs that are metabolized via these pathways are given in combination with GSK3640254. The study will consist of a Screening period and 3 sequential treatment regimens. Participants will be administered a single dose of probe substrate drugs (caffeine 200 milligram (mg), metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg and pravastatin 40 mg) on Day 1, followed by washout of 10 days. Participants will then receive GSK3640254 200 mg once daily on Days 11 to 20 followed by co-administration of probe substrate drugs with GSK3640254 on Day 21. The total duration of the study will be approximately 54 days including Screening. Approximately 20 participants will be treated in the study.
Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of caffeine.
Measure: Area under the plasma concentration-time curve (AUC) from time zero to time t (AUC[0-t]) for caffeine Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of caffeine.
Measure: AUC from time zero extrapolated to infinity (AUC[0-inf]) for caffeine Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of caffeine.
Measure: Maximum observed concentration (Cmax) for caffeine Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of caffeine.
Measure: Time of maximum observed concentration (Tmax) for caffeine Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of caffeine.
Measure: Apparent terminal phase half-life (t1/2) for caffeine Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Measure: AUC(0-t) for metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Measure: AUC(0-inf) for metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Measure: Cmax for metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Measure: Tmax for metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Measure: t1/2 for metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.
Measure: AUC(0-t) for montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.
Measure: AUC(0-inf) for montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.
Measure: Cmax for montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.
Measure: Tmax for montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.
Measure: t1/2 for montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Measure: AUC(0-t) for flurbiprofen Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Measure: AUC(0-inf) for flurbiprofen Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Measure: Cmax for flurbiprofen Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Measure: Tmax for flurbiprofen Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Measure: t1/2 for flurbiprofen Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Measure: AUC(0-t) for omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Measure: AUC(0-inf) for omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Measure: Cmax for omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Measure: Tmax for omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Measure: t1/2 for omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.
Measure: AUC(0-t) for midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.
Measure: AUC(0-inf) for midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.
Measure: Cmax for midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.
Measure: Tmax for midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.
Measure: t1/2 for midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.
Measure: AUC(0-t) for digoxin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.
Measure: AUC(0-inf) for digoxin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.
Measure: Cmax for digoxin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.
Measure: Tmax for digoxin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.
Measure: t1/2 for digoxin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Measure: AUC(0-t) for pravastatin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Measure: AUC(0-inf) for pravastatin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Measure: Cmax for pravastatin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Measure: Tmax for pravastatin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Measure: t1/2 for pravastatin Time: Day 1 to Day 26Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measure: Number of participants with adverse events (AEs) Time: Day 1 to Day 26Description: SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement.
Measure: Number of participants with serious adverse events (SAEs) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of platelets, white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils (Giga cells per Liter) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of absolute neutrophil count Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of hematocrit Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of hemoglobin (Hgb) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of Red blood cell (RBC) count Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of Mean corpuscular volume (MCV) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Absolute values of Mean corpuscular hemoglobin (MCH) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of blood urea nitrogen (BUN), sodium, glucose (fasting), potassium, phosphorus, calcium, chloride and carbon dioxide (Millimoles per Liter) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of anion gap Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of total cholesterol Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of triglycerides Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of creatinine, direct bilirubin, total bilirubin, and uric acid (Micromoles per Liter) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of albumin, globulin and total protein (Grams per Liter) Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lipase, amylase, lactate dehydrogenase (LDH) and creatinine phosphokinase (International Units per Liter) Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine specific gravity Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine potential of hydrogen (pH) Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine glucose Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine protein Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine blood Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine ketones Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine bilirubin and nitrite (Milligrams per deciliter) Time: Day 1 to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Absolute values of urine leukocyte esterase by dipstick Time: Day 1 to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in platelets, WBC count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils (Giga cells per Liter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in absolute neutrophil count (10^9 per Liter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in hematocrit Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in Hgb Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in RBC count Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in MCV Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of hematology parameters.
Measure: Change from Baseline in MCH Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in BUN, sodium, glucose (fasting), potassium, phosphorus, calcium, chloride and carbon dioxide (Millimoles per Liter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in anion gap Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in total cholesterol Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in triglycerides Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in creatinine, direct bilirubin, total bilirubin, and uric acid (Micromoles per Liter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in albumin, globulin and total protein (Grams per Liter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected for the assessment of clinical chemistry parameters.
Measure: Change from Baseline in ALT, AST, ALP, GGT, creatinine phosphokinase, lipase, amylase, and LDH (International Units per Liter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine specific gravity Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine pH Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine glucose Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine protein Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine blood Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine ketones Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine bilirubin and nitrite (Milligrams per deciliter) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Urine samples will be collected for the assessment of urine parameters.
Measure: Change from Baseline in urine leukocyte esterase by dipstick Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Twelve-lead ECGs will be obtained with the participant in a supine position after a rest of at least 10 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured.
Measure: Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds) Time: Day 1 to Day 26Description: Twelve-lead ECGs will be obtained with the participant in a supine position after a rest of at least 10 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured.
Measure: Change from Baseline in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Temperature will be assessed using an automated device.
Measure: Absolute values of oral temperature Time: Day 1 to Day 26Description: Temperature will be assessed using an automated device.
Measure: Change from Baseline in oral temperature Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Pulse rate will be assessed in the supine position with a completely automated device.
Measure: Absolute values of pulse rate Time: Day 1 to Day 26Description: Pulse rate will be assessed in the supine position with a completely automated device.
Measure: Change from Baseline in pulse rate Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Respiratory rate will be assessed in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions.
Measure: Absolute values of respiratory rate Time: Day 1 to Day 26Description: Respiratory rate will be assessed in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions.
Measure: Change from Baseline in respiratory rate Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood pressure will be assessed in the supine position with a completely automated device.
Measure: Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (Millimeters of mercury) Time: Day 1 to Day 26Description: Blood pressure will be assessed in the supine position with a completely automated device.
Measure: Change from Baseline in SBP and DBP (Millimeters of mercury) Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Oxygen saturation of participants will be assessed using pulse oximetry.
Measure: Absolute values of oxygen saturation Time: Day 1 to Day 26Description: Oxygen saturation of participants will be assessed using pulse oximetry.
Measure: Change from Baseline in oxygen saturation Time: Baseline (Day -1, Pre-dose) and up to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254
Measure: AUC(0-t) for GSK3640254 Time: Day 11 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254
Measure: AUC from time zero to the end of the dosing interval at steady state (AUC[0-tau]) for GSK3640254 Time: Day 11 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254
Measure: Cmax for GSK3640254 Time: Day 11 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254
Measure: Plasma concentration at the end of the dosing interval (Ctau) for GSK3640254 Time: Day 11 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254
Measure: Tmax for GSK3640254 Time: Day 11 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254
Measure: t1/2 for GSK3640254 Time: Day 11 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol.
Measure: AUC(0-t) for alpha-hydroxymetoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol.
Measure: AUC(0-inf) for alpha-hydroxymetoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol.
Measure: Cmax for alpha-hydroxymetoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol.
Measure: Tmax for alpha-hydroxymetoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol.
Measure: t1/2 for alpha-hydroxymetoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast.
Measure: AUC(0-t) for 36-hydroxymontelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast.
Measure: AUC(0-inf) for 36-hydroxymontelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast.
Measure: Cmax for 36-hydroxymontelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast.
Measure: Tmax for 36-hydroxymontelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast.
Measure: t1/2 for 36-hydroxymontelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole.
Measure: AUC(0-t) for 5-hydroxyomeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole.
Measure: AUC(0-inf) for 5-hydroxyomeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole.
Measure: Cmax for 5-hydroxyomeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole.
Measure: Tmax for 5-hydroxyomeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole.
Measure: t1/2 for 5-hydroxyomeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam.
Measure: AUC(0-t) for 1-hydroxymidazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam.
Measure: AUC(0-inf) for 1-hydroxymidazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam.
Measure: Cmax for 1-hydroxymidazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis 1-hydroxymidazolam.
Measure: Tmax for 1-hydroxymidazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam.
Measure: t1/2 for 1-hydroxymidazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin lactone.
Measure: AUC(0-t) for pravastatin lactone Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin lactone.
Measure: AUC(0-inf) for pravastatin lactone Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin lactone.
Measure: Cmax for pravastatin lactone Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin lactone.
Measure: Tmax for pravastatin lactone Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin lactone.
Measure: t1/2 for pravastatin lactone Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of Cmax of alpha-hydroxymetoprolol to metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of AUC(0-inf) of alpha-hydroxymetoprolol to metoprolol Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of Cmax of 36-hydroxymontelukast to montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of AUC(0-inf) of 36-hydroxymontelukast to montelukast Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of Cmax of 5-hydroxyomeprazole to omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of AUC(0-inf) of 5-hydroxyomeprazole to omeprazole Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of Cmax of 1-hydroxymidazolam to midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of AUC(0-inf) of 1-hydroxymidazolam to midazolam Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of Cmax of pravastatin lactone to pravastatin Time: Day 1 to Day 26Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis
Measure: Ratio of AUC(0-inf) of pravastatin lactone to pravastatin Time: Day 1 to Day 26"SKILLZ," is a mixed methods evaluation of the Grassroots Soccer (GRS) SKILLZ Package based in Lusaka, Zambia. The package is made up of three football-based programs: (1) SKILLZ-Girl - implemented in schools as part of a 10-week program culminating in a tournament event; (2) SKILLZ-Club - implemented as an ongoing extra-curricular activity after the completion of SKILLZ-Girl; (3) SKILLZ-Plus - a clinic based football group targeted at girls that are HIV-positive. The programs work together to build a continued support system which encourages uptake of Sexual Reproductive Health (SRH) and HIV services, while facilitating ART adherence (for HV-positive participants) and continued engagement with health services over the long-term (whether to contraceptive methods, HIV prevention services, HIV repeat testing, and/or HIV treatment and care). The study team has developed an enhanced SKILLZ-Girl offering, which will include a comprehensive module on HIVST, contraceptives and PrEP, access to a nurse during the implementation of sessions and the additional offering of HIVST and contraceptive services at the event along with ongoing engagement through the SKILLZ-Club program (Enhanced Arm) , The central hypothesis is that this enhanced curriculum will increase HIV testing and contraceptive uptake compared to the standard SKILLZ curriculum & standard event (SOC Arm). The investigators further hypothesize that the intervention in the enhanced arm will positively and directly affect a number of mediating factors including attendance at soccer events where community-based SRH services are offered, SRH knowledge, empowerment, self-confidence, and perceptions of gender balance, and (reduced) stigma. For girls found to be HIV-positive, the follow-on SKILLZ intervention (SKILLZ-Plus) has been designed to facilitate linkage to HIV care and treatment, reduce HIV-related stigma, increase disclosure to family and partners, increase feelings of social support, empowerment, self-efficacy, and ultimately adherence to ARVs, viral load suppression (VLS) and retention in HIV care and treatment. This study will be conducted in up to 32 secondary schools that GRS currently serves in the Lusaka Urban District.
Description: Number of participants, enrolled in the study, undergoing HIV testing (HIVST our Determine tests) over 2 years. Collected from facility testing registers and community testing registers.
Measure: Number of participants undergoing HIV testing within 24 months Time: 24 monthsDescription: Number of participants, enrolled in the study, accessing contraception, PreP or PEP over 2 years. Determined through the electronic medical record and clinic registers.
Measure: Number of participants accessing SRH related prevention services within 24 months Time: 24 monthsDescription: The percentage of participants, testing HIV positive, who have an undetectable viral load (as defined by the laboratory doing the test) after one year on treatment. Collected from routine laboratory data.
Measure: The percentage of HIV infected participants being virally suppressed at 12 months Time: 12 monthsDescription: The percentage of participants, testing HIV positive, who are actively retained in care at 3 months ie are not more than 7 days late for a scheduled appointment. Determined using the electronic medical record.
Measure: The percentage of HIV infected participants retained in care at 3 months Time: 3 monthsDescription: The percentage of participants, testing HIV positive, that have made their scheduled visit to the clinic within the first at 6 months of enrolment. (less than 7 days late), using the electronic medical record.
Measure: The percentage of HIV infected participants retained in care at 6 months Time: 6 monthsDescription: The percentage of participants, testing HIV positive, who attend their scheduled visits within the first 12 months of enrolment (less than seven days late). determined through the electronic medical record.
Measure: The percentage of HIV infected participants retained in care at 12 months Time: 12 monthsDescription: FGD's, IDI's and routine program data ( attendance registers, process data and documented observations) will be used to identify mediators, predictors, and barriers to uptake of the SKILLZ package after implementation
Measure: Conduct a process evaluation to describe how the intervention worked Time: 24 monthsDescription: Costs will include the personnel to manage the intervention, financial incentives and other related miscellaneous costs. These will be collected by the program manager and study team and will be based on actual costs.
Measure: Average short-term costs for the program implementation based on net-costs for the intervention. Time: Baseline through 12 monthsDescription: Each session that is conducted will be documented including number of participants in attendance (assessed voia attendance registers and routine program data).
Measure: Fidelity monitoring or adherence to the program as measured by the number of coaching sessions conducted per plan. Time: Baseline through 12 monthsDescription: Record and track key barriers through review of routine program data that prevent participants from engaging with the intervention. ie through review of the data collected by coaches from feedback from participants, FGD's and IDI's. During this COVID-19 period, we may be limited or may need to revise our anticipated collection of study results. The study record will reflect these changes as we navigate through the course of the study.
Measure: Identify barriers that prevent intervention participation Time: Baseline through 12 monthsThis is an active control, randomized study to investigate the safety, tolerability and PK of repeat dose administration of long acting CAB 400 mg/mL formulation intramuscular (IM) (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy adult participants. The study will assess the relative bioavailability of the CAB 400 mg/mL formulation administered by IM (vastus lateralis) and SC routes compared to the CAB 400 mg/mL administered via IM (gluteus medius) and also compared with historical data of CAB 200 mg/mL formulation administered via IM (gluteus medius). This is a two part study and will consist of a screening period, a 28-day oral lead-in with CAB 30 mg once daily, a 7 to 14-day washout period, an injection phase (up to Week 8 in Part 1 and up to Week 24 in Part 2) and a follow-up phase up to Week 52 post last injection.
Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Maximum observed Plasma concentration (Cmax) for cabotegravir (Part 1 Injection 1) Time: Pre-dose and at 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17 and 22Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Cmax for cabotegravir (Part 1 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Day 28/Week 4), 24 hours (Day 29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week 8), Week 12, 16, 24, 32, 40, 48 and 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Cmax for cabotegravir (Part 2 Injection 1) Time: Pre-dose, 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17, 22, Week 4, 6, 8 and 10Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Cmax for cabotegravir (Part 2 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Week 12-Day 1), 24 hours (Week 12-Day 2), Week 12-Day 3, Week 12-Day 5, Week 12-Day 6, Week 12-Day 7, Week 12-Day 8, Week 12-Day 10, Week 12-Day 14or15, Week 12-Day 17, Week 12-Day 22, Week 16, 18, 20, 22, 24, 36, 52 and 64Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Time of maximum observed plasma concentration (Tmax) for cabotegravir (Part 1 Injection 1) Time: Pre-dose, 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17 and 22Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Tmax for cabotegravir (Part 1 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Day 28/Week 4), 24 hours (Day 29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week 8), Week 12, 16, 24, 32, 40, 48 and 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Tmax for cabotegravir (Part 2 Injection 1) Time: Pre-dose, 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17, 22, Week 4, 6, 8 and 10Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Tmax for cabotegravir (Part 2 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Week 12-Day 1), 24 hours (Week 12-Day 2), Week 12-Day 3, Week 12-Day 5, Week 12-Day 6, Week 12-Day 7, Week 12-Day 8, Week 12-Day 10, Week 12-Day 14or15, Week 12-Day 17, Week 12-Day 22, Week 16, 18, 20, 22, 24, 36, 52 and 64Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Area under the concentration - time curve from time zero to last quantifiable time point (AUC[0-t]) for cabotegravir (Part 1 Injection 1) Time: Pre-dose and at 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17 and 22Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: AUC(0-t) for cabotegravir (Part 1 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Day 28/Week 4), 24 hours (Day 29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week 8), Week 12, 16, 24, 32, 40, 48 and 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: AUC(0-t) for cabotegravir (Part 2 Injection 1) Time: Pre-dose, 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17, 22, Week 4, 6, 8 and 10Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: AUC(0-t) for cabotegravir (Part 2 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Week 12-Day 1), 24 hours (Week 12-Day 2), Week 12-Day 3, Week 12-Day 5, Week 12-Day 6, Week 12-Day 7, Week 12-Day 8, Week 12-Day 10, Week 12-Day 14or15, Week 12-Day 17, Week 12-Day 22, Week 16, 18, 20, 22, 24, 36, 52 and 64Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Trough concentrations (Ctau) for cabotegravir (Part 1 Injection 1) Time: Pre-dose and at 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17 and 22Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Ctau for cabotegravir (Part 1 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Day 28/Week 4), 24 hours (Day 29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week 8), Week 12, 16, 24, 32, 40, 48 and 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Ctau for cabotegravir (Part 2 Injection 1) Time: Pre-dose, 1, 2, 8 hours (Day 1), 24 hours (Day 2), Day 3, 5, 6, 7, 8, 10, 14 or 15, 17, 22, Week 4, 6, 8 and 10Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Ctau for cabotegravir (Part 2 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Week 12-Day 1), 24 hours (Week 12-Day 2), Week 12-Day 3, Week 12-Day 5, Week 12-Day 6, Week 12-Day 7, Week 12-Day 8, Week 12-Day 10, Week 12-Day 14or15, Week 12-Day 17, Week 12-Day 22, Week 16, 18, 20, 22, 24, 36, 52 and 64Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Apparent terminal phase half-life (T½) for cabotegravir (Part 1 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Day 28/Week 4), 24 hours (Day 29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week 8), Week 12, 16, 24, 32, 40, 48 and 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: T½ for cabotegravir (Part 2 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Week 12-Day 1), 24 hours (Week 12-Day 2), Week 12-Day 3, Week 12-Day 5, Week 12-Day 6, Week 12-Day 7, Week 12-Day 8, Week 12-Day 10, Week 12-Day 14or15, Week 12-Day 17, Week 12-Day 22, Week 16, 18, 20, 22, 24, 36, 52 and 64Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: Absorption rate constant (KALA) for cabotegravir (Part 1 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Day 28/Week 4), 24 hours (Day 29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week 8), Week 12, 16, 24, 32, 40, 48 and 52Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
Measure: KALA for cabotegravir (Part 2 Injection 2) Time: Pre-dose, 1, 2, 8 hours (Week 12-Day 1), 24 hours (Week 12-Day 2), Week 12-Day 3, Week 12-Day 5, Week 12-Day 6, Week 12-Day 7, Week 12-Day 8, Week 12-Day 10, Week 12-Day 14or15, Week 12-Day 17, Week 12-Day 22, Week 16, 18, 20, 22, 24, 36, 52 and 64Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir. Geometric mean ratio of plasma Ctau of cabotegravir will be calculated for Cohorts 1, 2, 3, and 4 at Week 4 compared to historical CAB 200 mg/ml data (Week 8 Ctau following first injection at Week 4b in ATLAS [Study 201585]/FLAIR [Study 201584]).
Measure: Geometric mean ratio of plasma trough concentrations (Ctau) of cabotegravir for Cohorts 1, 2, 3, and 4 at Week 4 compared to historical CAB data at Week 8 Time: Pre-dose,1,2,8 hours (Day28/Week4) and at Week 4Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir. Geometric mean ratio of plasma trough concentrations (Ctau) of cabotegravir will be calculated for Cohorts 1, 2, 3, and 4 at Week 8 compared to historical CAB 200 mg/ml data (Week 12 Ctau following second injection at Week 8 in ATLAS [Study 201585]/FLAIR [Study 201584]).
Measure: Geometric mean ratio of plasma Ctau of cabotegravir for Cohorts 1, 2, 3, and 4 at Week 8 compared to historical CAB data at Week 12 Time: At Week 8 and at Week 12Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir. Geometric mean ratio of plasma Ctau of cabotegravir will be calculated for Cohorts 5 and 6 at Week 12 compared to historical CAB 200 mg/ml data (Week 8 Ctau following first injection at Week 4b in ATLAS [Study 201585]/FLAIR [Study 201584]).
Measure: Geometric mean ratio of plasma Ctau of cabotegravir for Cohorts 5 and 6 at Week 12 compared to historical CAB 200 data at Week 8 Time: At Week 12 and at Week 8Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir. Geometric mean ratio will be calculated by pair-wise comparisons between cohorts 1, 2, 3, and 4.
Measure: Geometric mean ratio of Plasma AUC(0-t) of cabotegravir Time: Pre-dose and at 1,2,8hours (Day 1), 24 hours (Day 2), Day 3,5,6,7,8,10,14 or 15,17 and 22(injection 1); Pre-dose, 1,2,8hours (Day 28/Week 4), 24hours (Day 29), Day 30,32,33,34,35,37,41,42,44,49,56 (Week 8), Week 12,16,24,32,40,48 and 52 (Injection 2)Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir. Geometric mean ratio will be calculated by pair-wise comparisons between cohorts 1, 2, 3, and 4.
Measure: Geometric mean ratio of Cmax of cabotegravir Time: Pre-dose, 1,2,8 hours(Day1), 24hours (Day2), Day3,5,6,7,8,10,14 or 15,17 and 22(injection 1); Pre-dose,1,2,8 hours(Day28/Week4), 24 hours(Day29), Day 30, 32, 33, 34, 35, 37, 41, 42, 44, 49, 56 (Week8), Week12, 16, 24, 32, 40, 48 and 52 (Injection 2)Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention
Measure: Number of participants with adverse events (AEs) (Part 1) Time: Up to 52 weeks post last injectionDescription: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention
Measure: Number of participants with AEs (Part 2) Time: Up to 52 weeks post last injectionDescription: PIN questionnaire contains 21 items that are grouped into 4 dimensions ("Acceptance of ISRs", "Bother of ISRs", "Sleep" and "Leg movement" and 5 individual items. Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 always equated with the most favorable perception of injection, and 5 the most unfavorable. PIN does not produce a total score.
Measure: Number of participants with acceptance of injection site reactions (ISRs) as assessed by Perception of Injection (PIN) questionnaire Time: At Day 8 post injectionDescription: Participants will be asked to rate their maximum level of pain since last assessment with the NRS on a scale of 0 (No pain) and 10 (extreme pain).
Measure: Number of participants with maximum level of pain assessed using Numeric Rating Scale (NRS) Time: At Days 1, 2, 5, 8 post each injectionDescription: Participants with liver biochemistry abnormalities will be assessed.
Measure: Number of participants with liver biochemistry abnormalities Time: Up to 52 weeks post last injectionInfection with HIV-1 continues to be a serious health threat throughout the world, with more than 40 million individuals infected worldwide. The current standard of care treatment for HIV-1 is combination anti-retroviral therapy (cART) with recommendations to start regardless of cluster of differentiation 4 (CD4) plus (+) T-cell count, committing people living with HIV to lifelong, lifesaving therapy. However, the chronic exposure to cART has identified anti-retroviral (ARV)-associated long-term toxicities (central nervous system [CNS] or cardiovascular [CV]/metabolic effects, renal disease), creating a need to address and prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 maturation inhibitor (MI) and has completed a short-term, monotherapy, proof of concept (POC) Phase 2a study. This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses [100, 150 and 200 milligrams {mg}]), active controlled clinical trial. It will aim to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine [ABC/3TC] or emtricitabine/tenofovir alafenamide [FTC/TAF]), in approximately 240 treatment-naïve HIV-1 infected adults. In the experimental arms, GSK3640254 will be administered in 3 blinded doses until the last participant completes their Week 48 study visit (Week 48 Secondary Endpoint study milestone). Thereafter, participants whose most recent HIV-1 ribonucleic acid (RNA) less than (<)50 copies/milliliters (c/mL) in the GSK3640254 arms will move into the Non-Randomised Phase and will be switched from their blinded dose to the open label optimal dose. Simultaneously, these participants will also be switched from their dual NRTI therapy to DTG. The total study duration will be approximately 7 years.
Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Week 24.
Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24 Time: At Week 24Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Weeks 48 and 96.
Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Weeks 48 and 96 Time: At Weeks 48 and 96Description: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.
Measure: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Change from Baseline in level of plasma HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.
Measure: Change from Baseline in plasma HIV-1 RNA at Weeks 24, 48 and 96 (c/mL) Time: Baseline and Weeks 24, 48 and 96Description: Absolute values of CD4+ cells at Weeks 24, 48, and 96 will be assessed.
Measure: Absolute values of CD4+ cell counts at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Change from Baseline in CD4+ cells at Weeks 24, 48 and 96 will be assessed.
Measure: Change from Baseline in CD4+ cell counts at Weeks 24, 48 and 96 (Cells per cubic millimeters [cells/mm^3]) Time: Baseline and Weeks 24, 48 and 96Description: All SAEs, deaths and AEs leading to treatment discontinuation will be assessed.
Measure: Number of participants with serious adverse events (SAEs), Deaths and adverse events (AEs) leading to treatment discontinuation at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: All AEs will be assessed.
Measure: Number of participants with AEs at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Severity of AEs will be assessed.
Measure: Severity of AEs at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Number of participants with AEs in GI, Psych/CNS will be assessed at Weeks 24, 48 and 96.
Measure: Number of participants with AEs in Gastrointestinal (GI), Psychological (Psych)/Central nervous system (CNS) at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Plasma samples will be collected for analyzing phenotypic resistance at Weeks 24, 48 and 96 using PhenoSense genotype testing (GT) for reverse transcriptase (RT) (NRTI and non-nucleoside reverse transcriptase inhibitors [NNRTI]) and Protease inhibitor (PI), PhenoSense Integrase, PhenoSense Gag assays for GSK3640254.
Measure: Number of participants who develop phenotypic resistance at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Plasma samples will be collected for analyzing genotypic resistance at Weeks 24, 48 and 96 using PhenoSense GT for RT and Protease genotype, GeneSeq Integrase, and Gag genotype (using a Next Generation Sequencing platform).
Measure: Number of participants who develop genotypic resistance at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: Maximum observed concentration (Cmax) of GSK3640254 at steady state at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: Cmax of GSK3640254 at steady state at Week 48 Time: At Week 48Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: AUC over the dosing interval (AUC [0-tau]) of GSK3640254 at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: AUC (0-tau) of GSK3640254 at steady state at Week 48 Time: At Week 48Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: Plasma concentration at the end of the dosing (Ctau) of GSK3640254 at steady state at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: Ctau of GSK3640254 at steady state at Week 48 Time: At Week 48Human immunodeficiency virus 1 (HIV-1) infections continues to be a serious health threat throughout the world and development of medicines with new mechanism of action have an important role to play. The purpose of this study is to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937. The information collected in this study will help in further clinical development of GSK3739937, including a Phase IIA Proof of Concept (PoC) study in HIV-infected participants as well as a FTIH study of long acting formulation of GSK3739937 administered parenterally (subcutaneously or intramuscularly). This randomized, placebo controlled, single and repeat-dose escalation study of GSK3739937 in healthy participants and will be executed in two-part. In Part 1 single ascending dose (SAD), approximately 18 participants will be randomized with approximately 9 participants within each of Cohort 1 and Cohort 2. In Part 2 multiple ascending dose (MAD), approximately 30 participants will be randomized with approximately 10 participants within each of Cohorts 3 to 5. Approximately 48 participants will be enrolled in the study and all doses will be administered after a moderate fat meal. Maximum duration of study participation will be approximately 22 weeks in Part 1 and approximately 18 weeks in Part 2.
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Part 1: Cohort 1-2: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Time: Up to Day 44Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets (Giga cells per liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameters: RBC count.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) count (Trillion cells per liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be e collected to analyze the hematology parameters: MCV.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Mean Corpuscular Volume (MCV) (Femtoliter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: MCH.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) (Picogram) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: percent of reticulocytes.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage of reticulocyte) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: Hb.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Hemoglobin (Hb) (Grams per deciliter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: ALT, AST, and ALP.
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphate (ALP) (International units per Liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.
Measure: Part 1:Cohort 1-2:Change from Baseline in bicarbonate,calcium,glucose,chloride,magnesium,phosphate,potassium,sodium,blood urea nitrogen (BUN),cholesterol,high density lipoprotein (HDL),low density lipoprotein (LDL),triglycerides (Millimole per Liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (units per liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, direct bilirubin and creatinine.
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: total protein.
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: total protein (Gram per Liter) Time: Baseline (Day -1) and up to Day 44Description: Urine samples will be collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measure: Part 1: Cohort 1-2: Number of Participants With Abnormal Urinalysis Time: Baseline (Day -1) and up to Day 44Description: SBP and DBP will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeters of mercury) Time: Baseline (Day -1) and up to Day 44Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute) Time: Baseline (Day -1) and up to Day 44Description: Temperature was will be in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Temperature (Degrees Celsius) Time: Baseline (Day -1) and up to Day 44Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute) Time: Baseline (Day -1) and up to Day 44Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Measure: Part 1: Cohort 1-2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Time: Baseline (Day 1, Pre-dose) and up to Day 44Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Part 2: Cohort 3-4: Number of Participants With AEs and SAEs Time: Up to Day 28Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measure: Part 2: Cohort 3-4:Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets (Giga cells per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameters: RBC count.
Measure: Part 2: Cohort 3-4:Change From Baseline in Hematology Parameters: RBC count (Trillion cells per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameters: MCV.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameters: MCV (Femtoliter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: MCH.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: MCH (Picogram) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: Percent of reticulocytes
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage reticulocyte) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: Hb.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Hb (Grams per deciliter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be e collected to analyze the chemistry parameter: ALT, AST and ALP.
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: ALT, AST and ALP (International units per Liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (units per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL and triglycerides.
Measure: Part 2: Cohort 3-4: Change From Baseline in bicarbonate, glucose, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL and triglycerides (Millimoles per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, creatinine and direct bilirubin
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinin and Direct Bilirubin (Micromoles per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: total protein.
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: Total protein (Grams per liter) Time: Baseline (Day -1) and up to Day 28Description: Urine samples collected at given time points to analyze the abnormal findings for pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measure: Part 2: Cohort 3-4: Number of Participants With Abnormal Urinalysis Time: Baseline (Day -1) and up to Day 28Description: SBP and DBP measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: DBP and SBP (Millimeters of mercury) Time: Baseline (Day -1) and up to Day 28Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute) Time: Baseline (Day -1) and up to Day 28Description: Temperature will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: Temperature (Degrees Celsius) Time: Baseline (Day -1) and up to Day 28Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute) Time: Baseline (Day -1) and up to Day 28Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Measure: Part 2: Cohort 3-4: Number of Participants With Abnormal ECG Findings Time: Baseline (Day -1) and up to Day 28Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Part 2: Cohort 5: Number of Participants With AEs and SAEs Time: Up to Day 42Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measure: Part 2: Cohort 5:Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets (Giga cells per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameters: RBC count
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameters: RBC count (Trillion cells per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameters: MCV.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameters: MCV (Femtoliter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: MCH.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: MCH (Picogram) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: Percent of reticulocytes
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage reticulocyte) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: Hb.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Hb (Grams per deciliter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be e collected to analyze the chemistry parameter: ALT, AST, and ALP.
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: ALT, AST, ALP (International units per Liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (Units per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL, and triglycerides.
Measure: Part 2: Cohort 5:Change From Baseline in Bicarbonate, glucose (non-fasting), Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglycerides (Millimoles per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, creatinine and direct bilirubin
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine and Direct Bilirubin (Micromoles per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: total protein.
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: Total protein (Grams per liter) Time: Baseline (Day -1) and up to Day 42Description: Urine samples collected at given time points to analyze the abnormal findings for pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measure: Part 2: Cohort 5: Number of Participants With Abnormal Urinalysis Time: Baseline (Day -1) and up to Day 42Description: SBP and DBP measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: DBP and SBP (Millimeters of mercury) Time: Baseline (Day -1) and up to Day 42Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute) Time: Baseline (Day -1) and up to Day 42Description: Temperature will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: Temperature (Degrees Celsius) Time: Baseline (Day -1) and up to Day 42Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute) Time: Baseline (Day -1) and up to Day 42Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Measure: Part 2: Cohort 5: Number of Participants With Abnormal ECG Findings Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-24) of GSK3739937.
Measure: Part 1: Cohort 1-2:Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 hours (AUC[0-24]) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-doseDescription: Blood samples will be collected at indicated time points for the PK analysis of AUC(0-t) of GSK3739937.
Measure: Part 1: Cohort 1-2: AUC From zero (pre-dose) to t (AUC [0-t]) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of AUC(0-inf) of GSK3739937.
Measure: Part 1: Cohort 1-2: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.
Measure: Part 1: Cohort 1-2: Apparent Terminal Phase Half-life (T1/2) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.
Measure: Part 1: Cohort 1-2: Apparent Oral Clearance (CL/F) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 1: Cohort 1-2: Maximum Observed Concentration (Cmax) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of C24 of GSK3739937.
Measure: Part 1: Cohort 1-2: Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 Time: At 24 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Clast of GSK3739937.
Measure: Part 1: Cohort 1-2: Last Quantifiable Concentration (Clast) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 1: Cohort 1-2: Time of Occurrence of Cmax (Tmax) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Tlag of GSK3739937.
Measure: Part 1: Cohort 1-2: Lag Time (Tlag) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Tlast of GSK3739937.
Measure: Part 1: Cohort 1-2: Time to Reach Clast (Tlast) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of AUC(0-24) of GSK3739937.
Measure: Part 2: Cohort 3-4: AUC (0-24) of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Cmax of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of C24 of GSK3739937.
Measure: Part 2: Cohort 3-4: C24 of GSK3739937 on Day 1 Time: At 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Tmax of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Tlag of GSK3739937.
Measure: Part 2: Cohort 3-4: Tlag of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Tmax of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Cmax of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) of GSK3739937.
Measure: Part 2: Cohort 3-4: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Ctau of GSK3739937.
Measure: Part 2: Cohort 3-4: Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14 Time: At 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.
Measure: Part 2: Cohort 3-4: T1/2 of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours on Day 14Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.
Measure: Part 2: Cohort 3-4: CL/F of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 2: Cohort 5: Tmax of GSK3739937 on Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 2: Cohort 5: Cmax of GSK3739937 on Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) of GSK3739937.
Measure: Part 2: Cohort 5: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Ctau of GSK3739937.
Measure: Part 2: Cohort 5: Plasma Trough Concentration (Ctau) of GSK3739937: Day 28 Time: At 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.
Measure: Part 2: Cohort 5:T1/2 of GSK3739937: Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.
Measure: Part 2: Cohort 5: CL/F of GSK3739937: Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-inf) Following Single Dose of GSK3739937.
Measure: Part 1: Cohort 1-2: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Cmax Following Single Dose of GSK3739937.
Measure: Part 1: Cohort 1-2: Dose Proportionality for Cmax Following Single Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 3-4: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 5: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Ctrough Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 3-4: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3739937 Time: At 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Ctrough Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 5: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3739937 Time: At 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 3-4: Dose Proportionality (Cmax) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 5: Dose Proportionality (Cmax) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Predicted accumulation ratio Rp based on AUC.
Measure: Part 1: Cohort 1-2: Predicted accumulation ratio Rp based on AUC Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]).
Measure: Part 2: Cohort 3-4: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 14Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]).
Measure: Part 2: Cohort 5: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 28Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of Cmax (R [CMAX]).
Measure: Part 2: Cohort 3-4: Accumulation Ratio of Cmax (R [CMAX]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 14Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of Cmax (R [CMAX]).
Measure: Part 2: Cohort 5: Accumulation Ratio of Cmax (R [CMAX]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 28Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of C(Tau) (R[CTAU]).
Measure: Part 2: Cohort 3-4: Accumulation Ratio of C(Tau) (R[CTAU]) Time: At 24 hours post-dose on Day 1 and Day 14Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of C(Tau) (R[CTAU]).
Measure: Part 2: Cohort 5: Accumulation Ratio of C(Tau) (R[CTAU]) Time: At 24 hours post-dose on Day 1 and Day 28Description: Blood samples will be collected at indicated time points for the analysis of pre-dose Concentration of GSK3739937.
Measure: Part 2: Cohort 3-4: Pre-dose Concentration of GSK3739937 from Day 2 to Day 14 Time: Pre-dose from Day 2 to Day 14Description: Blood samples will be collected at indicated time points for the analysis of Pre-dose Concentration of GSK3739937.
Measure: Part 2: Cohort 5: Pre-dose Concentration of GSK3739937 from Day 2 to Day 28 Time: Pre-dose from Day 2 to Day 28This is an open-label, single-center, single group, non-randomized, two-period, single sequence, mass balance study which will enroll 6 healthy male participants. This study will assess the pharmacokinetics, balance/excretion, and metabolism of GSK3640254 in humans using [14C]-radiolabeled drug substance administered as an intravenous (IV) infusion and via the oral route. The study will also provide an assessment of GSK3640254 absorption, metabolism and excretion following administration of a [14C]-radiolabeled oral suspension. Each participant will be involved in the study for up to 10 weeks which will include a screening period, two treatment periods (treatment Periods 1 and 2) separated by a washout of at least 13 days between oral doses, and a follow-up visit 7-14 days after the last assessment in treatment Period 2.
Description: Blood samples will be collected at the indicated time points to evaluate [14C]-GSK3640254 in plasma.
Measure: Treatment period 1: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) in plasma following administration of IV dose of 14 Carbon [14C]-GSK3640254 Time: Day 1 (Pre-dose, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 1: AUC(0-inf) in plasma following administration of oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 1: AUC(0-inf) of total radioactivity in plasma following administration of IV dose of [14C]-GSK3640254 Time: Screening, Day-1, Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 2: AUC(0-inf) in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 2: AUC(0-inf) of total radioactivity in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate [14C]-GSK3640254 in plasma.
Measure: Treatment period 1: AUC from time zero (pre-dose) to last time of quantifiable concentration within a participant across all treatments (AUC[0-t]) in plasma following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 1: AUC (0-t) in plasma following administration of oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 1: AUC(0-t) of total radioactivity in plasma following administration of IV dose of [14C]-GSK3640254 Time: Screening, Day-1, Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 2: AUC (0-t) in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 2: AUC(0-t) of total radioactivity in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate [14C]-GSK3640254 in plasma.
Measure: Treatment period 1: Maximum observed concentration (Cmax) in plasma following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 1:Cmax in plasma following administration of oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 1: Cmax of total radioactivity in plasma following administration of IV dose of [14C]-GSK3640254 Time: Screening, Day-1, Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 2: Cmax in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-doseDescription: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 2: Cmax of total radioactivity in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in blood.
Measure: Treatment period 2: Cmax of total radioactivity in blood following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (2, 4, 6, 8, 10 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate [14C]-GSK3640254 in plasma.
Measure: Treatment period 1:Time of occurrence of Cmax (Tmax) in plasma following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 1:Tmax in plasma following administration of oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 1: Tmax of total radioactivity in plasma following administration of IV dose of [14C]-GSK3640254 Time: Screening, Day-1, Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 2: Tmax in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 2: Tmax of total radioactivity in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in blood.
Measure: Treatment period 2: Tmax of total radioactivity in blood following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (2, 4, 6, 8, 10 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate [14C]-GSK3640254 in plasma.
Measure: Treatment period 1:Terminal phase half-life (T1/2) in plasma following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 1: T1/2 in plasma following administration of oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 1: T1/2 of total radioactivity in plasma following administration of IV dose of [14C]-GSK3640254 Time: Screening, Day-1, Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate GSK3640254 in plasma.
Measure: Treatment period 2: T1/2 in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points to evaluate total radioactivity in plasma.
Measure: Treatment period 2: T1/2 of total radioactivity in plasma following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of [14C]-GSK3640254.
Measure: Treatment period 1: Volume of distribution at steady state (Vss) following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of [14C]-GSK3640254.
Measure: Treatment period 1: Total systemic clearance (CL) following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Urine samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Renal clearance (CLr) following administration of IV dose of GSK3640254 Time: Day 1 (Pre-dose), 0-24 Hours, 24-48 Hours, 48-72 Hours, 72-96 Hours, 96-120 Hours, 120-144 Hours, 144-168 HoursDescription: Urine samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 2: CLr following administration of oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose), 0-24 Hours, 24-48 Hours, 48-72 Hours, 72-96 Hours, 96-120 Hours, 120-144 Hours, 144-168 HoursDescription: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Oral Clearance (CL/F) following oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 2: CL/F following oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Apparent volume of distribution (Vz/F) following oral dose of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 2: Vz/F following oral dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Absolute oral bioavailability (F) of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Percentage of drug escaping first pass hepatic clearance (Fh) following administration of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8,9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Percentage of drug absorbed (Fa) following administration of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Measure: Treatment period 1: Percentage of drug escaping gut metabolism (Fg) following administration of GSK3640254 Time: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168 hours post-dose)Description: Urine samples will be collected at the indicated time points to determine total radioactivity in urine.
Measure: Treatment period 1: Percentage of total radioactive dose in urine following administration of IV dose of [14C]-GSK3640254 Time: Day 1 (Pre-dose), 0-24 Hours, 24-48 Hours, 48-72 Hours 72 - 96 Hours, 96-120 Hours, 120-144 Hours, 144-168 HoursDescription: Urine samples will be collected at the indicated time points to determine total radioactivity in urine.
Measure: Treatment period 2: Percentage of the total radioactive dose in urine following administration of oral dose of [14C]-GSK3640254 Time: 0-24 Hours, 24-48 Hours, 48-72 Hours, 72-96 Hours, 96-120 Hours, 120-144 Hours, 144-168 HoursDescription: Fecal samples will be collected at the indicated time points to determine total radioactivity in feces.
Measure: Treatment period 1: Percentage of total radioactive dose in feces following administration of IV dose of [14C]-GSK3640254 Time: 0-24 Hours, 24-48 Hours, 48- 72 Hours, 72-96 Hours, 96-120 Hours, 120-144 Hours, 144-168 Hours.Description: Fecal samples will be collected at the indicated time points to determine total radioactivity in feces.
Measure: Treatment period 2: Percentage of total radioactive dose in feces following administration of oral dose of [14C]-GSK3640254 Time: 0-24 Hours, 24-48 Hours, 48-72 Hours, 72-96 Hours, 96-120 Hours, 120-144 Hours, 144-168 Hours.Description: AEs and SAEs will be collected.
Measure: Number of participants With Adverse Events (AEs) and Serious AEs (SAEs) Time: Up to 50 daysDescription: Blood samples and urine samples will be collected for assessment of hematology, clinical chemistry and urine parameters.
Measure: Number of participants with abnormal hematology, clinical chemistry and urinalysis parameters Time: Day -1, Day 2 (36 hours), Day 5 , Day 8 and up to 50 daysDescription: Single12-lead ECG will be recorded with the participant in a supine position. Number of participants with abnormal ECG findings will be assessed.
Measure: Number of participants with abnormal 12-lead electrocardiogram (ECG) Time: Up to 50 daysDescription: Number of participants with abnormal vital signs will be assessed.
Measure: Number of participants with abnormal vital signs Time: Up to 50 daysDescription: Blood samples will be collected at the indicated time points to evaluate total radioactivity following administration of oral dose of [14C]-GSK3640254.
Measure: Treatment Period 2: Total radioactivity in blood to plasma following administration of oral dose of [14C]-GSK3640254 Time: 2 Hours, 4 Hours, 6 Hours, 8 Hours, and 10 HoursNorth-east area of France was hit in February 2020 by the new coronavirus disease, more severely than other French regions. Factors affecting the evolution of the disease and its severity have been quickly identified, among them figuring different kinds of immune deficiency. Even if nowadays HIV infection is usually well controlled by ARV drugs, those patients with uncontrolled viral load and/or low CD4 cell counts, remain at higher risk of severe COVID infection. In this context, the primary objective of our study is aimed at evaluating the prevalence of SARS-CoV-2 antibodies in a cohort of HIV-infected patients followed-up in an HIV-infection care center. Secondary objectives are: evaluating whether the antibodies are protective or not, the kinetic of these antibodies, and HIV associated factors with the presence of antibodies.
Description: SARS-CoV-2 antibodies will be detected with a rapid test detecting IgG and IgM, at inclusion, and during a 6-month and a 12-month visit, in order to assess the prevalence of the virus in this population.
Measure: Seroprevalence of SARS-CoV-2 Time: From baseline to 12 monthsHuman immunodeficiency virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) is a worldwide epidemic that continues to grow significantly causing new infections and related deaths per year. Chronic HIV infection in adults continues to be characterized by increased development and transmission of resistant virus and issues associated with long-term toxicity of antiretroviral therapy (ART). The current paradigm in the treatment of HIV involves life-long therapy with multiple antiretrovirals (ARVs). This dependency on medical therapy requires a need for continuous improvement on the durability, tolerability and convenience of all antiretroviral classes. This is a Phase IIIb, randomized, open-label, active-controlled, multicenter, parallel-group, non-inferiority study (SOLAR: Switch Onto Long Acting Regimen). It is designed to assess the antiviral activity and safety of a two-drug regimen of CAB LA + RPV LA administered every 2 months (Q2M) compared with maintenance of BIK. Approximately 654 adult HIV-1 infected participants who are on the stable ARV regimen BIK will be randomized in a 2:1 ratio to either be switched to the CAB LA + RPV LA regimen or continue BIK through 12 months. The study will continue with an Extension Phase after Month 12 Oral Lead-In (OLI) and BIK/Month 11 Direct to Injection (D2I). BIKTARVY is a registered trademark of Gilead Sciences.
Description: Participants with plasma HIV-1 RNA >=50 c/mL per Food and Drug Administration (FDA) snapshot algorithm will be assessed.
Measure: Percentage of participants with plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) greater than or equal to (>=) 50 copies per mL (c/mL) - OLI Time: At Month 12Description: Participants with plasma HIV-1 RNA >=50 c/mL per FDA snapshot algorithm will be assessed.
Measure: Percentage of participants with plasma HIV-1 RNA >=50 c/mL - D2I Time: At Month 11Description: Participants with plasma HIV-1 RNA >=50 c/mL per FDA snapshot algorithm will be assessed.
Measure: Percentage of participants with plasma HIV-1 RNA >=50 c/mL - BIK Time: At Month 12Description: Participants with plasma HIV-1 RNA <50 c/mL per FDA snapshot algorithm will be assessed.
Measure: Percentage of participants with plasma HIV-1 RNA less than (<)50 c/mL - OLI Time: At Months 6 and 12Description: Participants with plasma HIV-1 RNA <50 c/mL per FDA snapshot algorithm will be assessed.
Measure: Percentage of participants with plasma HIV-1 RNA <50 c/mL - D2I Time: At Months 5 and 11Description: Participants with plasma HIV-1 RNA <50 c/mL per FDA snapshot algorithm will be assessed.
Measure: Percentage of participants with plasma HIV-1 RNA <50 c/mL - BIK Time: At Months 6 and 12Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
Measure: Percentage of participants with protocol-defined confirmed virologic failure (CVF) - OLI Time: Up to Month 12Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
Measure: Percentage of participants with protocol-defined CVF - D2I Time: Up to Month 11Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
Measure: Percentage of participants with protocol-defined CVF - BIK Time: Up to Month 12Description: Participants with plasma HIV-1 RNA >=50 c/mL will be assessed per FDA snapshot algorithm.
Measure: Percentage of participants with HIV-RNA >= 50 c/mL - OLI Time: At Month 6Description: Participants with plasma HIV-1 RNA >=50 c/mL will be assessed per FDA snapshot algorithm.
Measure: Percentage of participants with HIV-RNA >= 50 c/mL - D2I Time: At Month 5Description: Participants with plasma HIV-1 RNA >=50 c/mL will be assessed per FDA snapshot algorithm.
Measure: Percentage of participants with HIV-RNA >= 50 c/mL - BIK Time: At Month 6Description: Absolute values of HIV viral load will be assessed.
Measure: Absolute values of HIV viral load - OLI Time: At Months 6 and 12Description: Absolute values of HIV viral load will be assessed.
Measure: Absolute values of HIV viral load - D2I Time: At Months 5 and 11Description: Absolute values of HIV viral load will be assessed.
Measure: Absolute values of HIV viral load - BIK Time: At Months 6 and 12Description: Change from Baseline in HIV viral load will be assessed.
Measure: Change from Baseline in HIV viral load (c/mL) - OLI Time: Baseline (Day 1) and at Months 6 and 12Description: Change from Baseline in HIV viral load will be assessed.
Measure: Change from Baseline in HIV viral load (c/mL) - D2I Time: Baseline (Day 1) and at Months 5 and 11Description: Change from Baseline in HIV viral load will be assessed.
Measure: Change from Baseline in HIV viral load (c/mL) - BIK Time: Baseline (Day 1) and at Months 6 and 12Description: Absolute values of CD4+ cell counts will be assessed.
Measure: Absolute values of cluster of differentiation 4 plus (CD4+) cell counts - OLI Time: At Months 6 and 12Description: Absolute values of CD4+ cell counts will be assessed.
Measure: Absolute values of CD4+ cell counts - D2I Time: At Months 5 and 11Description: Absolute values of CD4+ cell counts will be assessed.
Measure: Absolute values of CD4+ cell counts - BIK Time: At Months 6 and 12Description: Change from Baseline in CD4+ cell will be assessed.
Measure: Change from Baseline in CD4+ cell counts (Cells per cubic millimeters [cells/mm^3]) - OLI Time: Baseline (Day 1) and at Months 6 and 12Description: Change from Baseline in CD4+ cell will be assessed.
Measure: Change from Baseline in CD4+ cell counts (cells/mm^3) - D2I Time: Baseline (Day 1) and at Months 5 and 11Description: Change from Baseline in CD4+ cell will be assessed.
Measure: Change from Baseline in CD4+ cell counts (cells/mm^3) - BIK Time: Baseline (Day 1) and at Months 6 and 12Description: Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent phenotypic resistance to CAB, RPV, BIC, FTC, and TAF.
Measure: Number of participants with treatment-emergent phenotypic resistance - OLI Time: Up to Month 12Description: Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent phenotypic resistance to CAB, RPV, BIC, FTC, and TAF.
Measure: Number of participants with treatment-emergent phenotypic resistance - D2I Time: Up to Month 11Description: Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent phenotypic resistance to CAB, RPV, BIC, FTC, and TAF.
Measure: Number of participants with treatment-emergent phenotypic resistance - BIK Time: Up to Month 12Description: Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent genotypic resistance to CAB, RPV, BIC, FTC, and TAF.
Measure: Number of participants with treatment-emergent genotypic resistance - OLI Time: Up to Month 12Description: Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent genotypic resistance to CAB, RPV, BIC, FTC, and TAF.
Measure: Number of participants with treatment-emergent genotypic resistance - D2I Time: Up to Month 11Description: Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent genotypic resistance to CAB, RPV, BIC, FTC, and TAF.
Measure: Number of participants with treatment-emergent genotypic resistance - BIK Time: Up to Month 12Description: Blood and urine samples will be collected over time to assess renal and bone biomarkers.
Measure: Number of participants with abnormal renal and bone biomarkers - OLI Time: At Months 6 and 12Description: Blood and urine samples will be collected over time to assess renal and bone biomarkers.
Measure: Number of participants with abnormal renal and bone biomarkers - D2I Time: At Months 5 and 11Description: Blood and urine samples will be collected over time to assess renal and bone biomarkers.
Measure: Number of participants with abnormal renal and bone biomarkers - BIK Time: At Months 6 and 12Description: Metabolic syndrome is a cluster of conditions that occurs together increasing one's risk of heart disease, stroke and type 2 diabetes mellitus (DM). These conditions include increased blood pressure (BP), elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and triglyceride (TG) levels.
Measure: Percentage of participants with Metabolic syndrome - OLI Time: At Months 6 and 12Description: Metabolic syndrome is a cluster of conditions that occurs together increasing one's risk of heart disease, stroke and type 2 DM. These conditions include increased BP, elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and TG levels.
Measure: Percentage of participants with Metabolic syndrome - D2I Time: At Months 5 and 11Description: Metabolic syndrome is a cluster of conditions that occurs together increasing one's risk of heart disease, stroke and type 2 DM. These conditions include increased BP, elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and TG levels.
Measure: Percentage of participants with Metabolic syndrome - BIK Time: At Months 6 and 12Description: Insulin resistance will be assessed using homeostasis model of assessment-insulin resistance (HOMA-IR) Score.
Measure: Number of participants with insulin resistance - OLI Time: At Months 6 and 12Description: Insulin resistance will be assessed using HOMA-IR Score.
Measure: Number of participants with insulin resistance - D2I Time: At Months 5 and 11Description: Insulin resistance will be assessed using HOMA-IR Score.
Measure: Number of participants with insulin resistance -BIK Time: At Months 6 and 12Description: The "Preference" questionnaire will include 3 questions and assess whether participants prefer the CAB LA + RPV LA injectable treatment or the daily oral ARV regimen, also evaluating the attributes supporting this preference.
Measure: Percentage of participants with their treatment Preference as Assessed Using Preference Questionnaire - OLI Time: At Month 12Description: The "Preference" questionnaire will include 3 questions and assess whether participants prefer the CAB LA + RPV LA injectable treatment or the daily oral ARV regimen, also evaluating the attributes supporting this preference.
Measure: Percentage of participants with their Treatment Preference as Assessed Using Preference Questionnaire - D2I Time: At Month 11Description: The "Preference" questionnaire will include 3 questions and assess whether participants prefer the CAB LA + RPV LA injectable treatment or the daily oral ARV regimen, also evaluating the attributes supporting this preference.
Measure: Percentage of Participants with their treatment Preference as Assessed Using Preference Questionnaire - BIK Time: At Month 12Description: The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks.
Measure: Change From Baseline in Total Treatment Satisfaction Score using HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) (scores on a scale) - OLI Time: Baseline (Day 1) and at Months 6 and 12Description: The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks.
Measure: Change From Baseline in Total Treatment Satisfaction Score using HIVTSQs (scores on a scale) - D2I Time: Baseline (Day 1) and at Months 5 and 11Description: The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks.
Measure: Change From Baseline in Total Treatment Satisfaction Score using HIVTSQs (scores on a scale)- BIK Time: Baseline (Day 1) and at Months 6 and 12Description: HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment.
Measure: Change From Baseline in individual item scores using HIVTSQs (scores on a scale) - OLI Time: Baseline (Day 1) and at Months 6 and 12Description: HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment.
Measure: Change From Baseline in individual item scores using HIVTSQs (scores on a scale) - D2I Time: Baseline (Day 1) and at Months 5 and 11Description: HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment.
Measure: Change From Baseline in individual item scores using HIVTSQs (scores on a scale) - BIK Time: Baseline (Day 1) and at Months 6 and 12Description: The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 will represent no change.
Measure: Number of participants with change in treatment satisfaction over time using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc)- OLI Time: At Month 12Description: The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 will represent no change.
Measure: Number of participants with change in treatment satisfaction over time using HIVTSQc - D2I Time: At Month 11Description: The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 will represent no change.
Measure: Number of participants with change in treatment satisfaction over time using HIVTSQc - BIK Time: At Month 12Description: The PIN questionnaire explores the bother of pain at the injection site and injection site reaction (ISRs), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections. This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial. The items in the scale are rated on a 5-point scale and questions are phrased in such a way as to ensure that 1 is always equated with the most favorable perception of vaccination, and 5 is the most unfavorable.
Measure: Number of participants with change in Dimension Scores Using Perception of Injection (PIN) Questionnaire - OLI Time: At Months 2, 6, and 12Description: The PIN questionnaire explores the bother of pain at the injection site and injection site reaction (ISRs), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections. This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial. The items in the scale are rated on a 5-point scale and questions are phrased in such a way as to ensure that 1 is always equated with the most favorable perception of vaccination, and 5 is the most unfavorable.
Measure: Number of participants with change in Dimension Scores Using PIN Questionnaire - D2I Time: At Months 1, 5, and 11This study will aim to evaluate the effect of therapeutic and supratherapeutic oral doses of GSK3640254 on cardiac conduction compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. The study has 2 parts: Part 1 will determine the supratherapeutic dose for Part 2, which will be the main corrected QT interval (QTc) study. Part 1 consists of 2 sequential cohorts: Sentinel Cohort 1 will evaluate once daily (QD) dosing of GSK3640254 or placebo for 7 days and Sentinel Cohort 2 will evaluate twice daily (BID) dosing of GSK3640254 or placebo for 7 days. Part 2 will investigate the safety, tolerability and Pharmacokinetics (PK) of GSK3640254 doses on cardiac conduction as compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. Moxifloxacin will be included as a positive control. All doses of study intervention will be administered under fed conditions and will receive a moderate-fat meal 30 minutes prior to dosing. The total duration of the study is approximately 91 days. Approximately 58 participants will be enrolled in the study.
Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Area under the plasma concentration-time curve from time zero to time t (AUC[0-t]) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: AUC from time zero to the end of the dosing interval at steady state (AUC[0-tau]) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Maximum observed concentration (Cmax) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Plasma concentration at the end of the dosing interval (Ctau) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Time of maximum observed concentration (Tmax) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected for measurement of plasma concentrations of GSK3640254 and its major metabolite.
Measure: Part 1: Plasma concentrations of GSK3640254 and its major metabolite Time: Up to Day 9 of each cohortDescription: All AEs and SAEs will be assessed.
Measure: Part 1: Number of participants with adverse events (AEs) and serious AEs (SAEs) Time: Up to Day 9 of each cohortDescription: Blood samples will be collected for the assessment of hematology and chemistry parameters.
Measure: Part 1: Number of participants with abnormal laboratory parameters Time: Up to Day 9 of each cohortDescription: Urine samples will be collected for the assessment of urinalysis parameters.
Measure: Part 1: Number of participants with abnormal urinalysis parameters Time: Up to Day 9 of each cohortDescription: Number of participants with abnormal ECG parameters will be assessed.
Measure: Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters Time: Up to Day 9 of each cohortDescription: Number of participants with abnormal vital signs will be assessed.
Measure: Part 1: Number of participants with abnormal vital signs Time: Up to Day 9 of each cohortDescription: Placebo-corrected change from Baseline in QTcF will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in QT interval corrected for heart rate using Fridericia's formula (QTcF) following administration of GSK3640254 (Milliseconds [ms]) Time: Baseline (Day -1) and up to Day 51Description: Blood samples will be collected for measurement of plasma concentrations of GSK3640254 and its major metabolite.
Measure: Part 2: Plasma concentrations of GSK3640254 and its major metabolite Time: Up to Day 51Description: Change from Baseline in heart rate will be analyzed.
Measure: Part 2: Change from Baseline in heart rate (HR) (Beats per minute [bpm]) Time: Baseline (Day -1) and up to Day 51Description: Change from Baseline in QTcF, PR interval and QRS interval will be analyzed.
Measure: Part 2: Change from Baseline in QTcF, PR interval and QRS interval (ms) Time: Baseline (Day -1) and up to Day 51Description: Placebo-corrected change from Baseline in HR will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in HR (bpm) Time: Baseline (Day -1) and up to Day 51Description: Placebo-corrected change from Baseline in QTcF, PR interval and QRS interval will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in QTcF, PR interval and QRS interval (ms) Time: Baseline (Day -1) and up to Day 51Description: Number of participants with abnormal HR, QTcF, PR interval and QRS interval will be assessed.
Measure: Part 2: Number of participants with abnormal HR, QTcF, PR interval and QRS interval Time: Up to Day 51Description: Number of participants with treatment emergent changes of T-wave morphology will be evaluated.
Measure: Part 2: Number of participants with treatment emergent changes of T-wave morphology Time: Up to Day 51Description: Number of participants with presence of U-wave will be evaluated.
Measure: Part 2: Number of participants with presence of U-wave Time: Up to Day 51Description: Placebo-corrected change from Baseline in QTcF will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in QTcF following administration of Moxifloxacin (ms) Time: Baseline (Day -1) and up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: AUC(0-t) of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: AUC(0-tau) of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: Cmax of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: Ctau of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: Tmax of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of Moxifloxacin.
Measure: Part 2: Cmax of Moxifloxacin Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of Moxifloxacin.
Measure: Part 2: Tmax of Moxifloxacin Time: Up to Day 51Description: All AEs and SAEs will be assessed.
Measure: Part 2: Number of participants with AEs and SAEs Time: Up to Day 51Description: Blood samples will be collected for the assessment of hematology and chemistry parameters.
Measure: Part 2: Number of participants with abnormal laboratory parameters Time: Up to Day 51Description: Urine samples will be collected for the assessment of urinalysis parameters.
Measure: Part 2: Number of participants with abnormal urinalysis parameters Time: Up to Day 51Description: Number of participants with abnormal ECG parameters will be assessed.
Measure: Part 2: Number of participants with abnormal ECG parameters Time: Up to Day 51Description: Number of participants with abnormal vital signs will be assessed.
Measure: Part 2: Number of participants with abnormal vital signs Time: Up to Day 51The purpose of the study is to assess seroprevalence of COVID-19 infection in a cohort of HIV + patients and in a cohort of patients taking PrEP by emtricitabine / tenofovir.
Description: % of anti-covid positive cells
Measure: Presence and quantification of CD4 / CD8 reactivity to COVID-19 epitopes in patient with positive and negative serological tests for covid-19 Time: 3 monthsThe non-essential and non-urgent follow-up consultations of patients living with HIV were postponed or transformed into "teleconsultation" or exchanges of e-mails between practitioners and patients during COVID-19 epidemic. This change in care can have an impact on follow-up and access to treatment for PVVIH.
Description: Determination of the number of patients with microbiologically or clinically-biologically proven SARS CoV2 infection at inclusion in the study
Measure: Prevalence of SARS CoV2 infection in PVVIH in Hauts de France Time: InclusionDescription: Determination of the number of patients with microbiologically or clinically-biologically proven SARS CoV2 infection at the end of the study
Measure: Prevalence of SARS CoV2 infection in PVVIH in Hauts de France Time: through study completion, an average of 19 monthsDescription: Percentage of patients who stopped their antiretroviral treatment
Measure: Determine the incidence rate of COVID 19 among PVVIH antiretroviral treatment Time: through study completion, an average of 19 monthsDescription: Reason for discontinuing antiretroviral treatment
Measure: Determine the incidence rate of COVID 19 among PVVIH discontinuing antiretroviral treatment Time: through study completion, an average of 19 monthsDescription: Percentage of patients who stopped all follow-up by an infectious disease specialist
Measure: Determine the incidence rate of COVID 19 among PVVIH who stopped all follow-up Time: through study completion, an average of 19 monthsDescription: Evaluation of the psychological scales HAD on PVVIH
Measure: Psychological consequences of this epidemic among PVVIH : HAD Time: through study completion, an average of 19 monthsDescription: Evaluation of the psychological scales PROQOL-HIV on PVVIH
Measure: Psychological consequences of this epidemic among PVVIH : PROQOL-HIV Time: through study completion, an average of 19 monthsThis study will evaluate the safety and immune response in healthy HIV-exposed and uninfected infants to the protein vaccine, CH505TF gp120, adjuvanted with GLA-SE.
Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Measure: Local reactogenicity signs and symptoms Time: Measured through week 55Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Measure: Systemic reactogenicity signs and symptoms Time: Measured through week 55Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Measure: Frequency of adverse events (AEs) Time: Measured through week 106Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Measure: Frequency of serious adverse events (SAEs) Time: Measured through week 106Description: Measured by Binding antibody multiplex assay (BAMA)
Measure: Magnitude of HIV-1 specific serum IgG binding antibodies Time: Measured at week 56Description: Measured by flow cytometry
Measure: Quantification of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site Time: Measured at week 18Description: Measured by flow cytometry
Measure: Quantification of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site Time: Measured at week 56Description: Measured by flow cytometry
Measure: Phenotypic characterization of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site Time: Measured at week 18Description: Measured by flow cytometry
Measure: Phenotypic characterization of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site Time: Measured at week 56Description: Measured by Pediatric Vaccine Multiplex Assay (PVMA)
Measure: EPI vaccine-specific antibody responses Time: Measured at week 56Description: Measured by TZM-bl assay
Measure: Magnitude of serum neutralization of vaccine-matched viral isolates, and viruses engineered to detect precursors of CD4 binding site and V1V2 antibodies Time: Measured at week 56Description: Measured by TZM-bl assay
Measure: Serum neutralization of vaccine-matched viral isolates, and viruses engineered to detect precursors of CD4 binding site and V1V2 antibodies Time: Measured at week 56Description: Measured by BAMA
Measure: Response rate of vaccine-elicited serum binding antibodies to FcR proteins Time: Measured at week 56Description: Measured by BAMA
Measure: Magnitude of vaccine-elicited serum binding antibodies to FcR proteins Time: Measured at week 56Description: Measured by flow cytometry and/or luciferase assays
Measure: Response rate of serum Antibody-dependent cellular cytotoxicity (ADCC) Time: Measured at week 56Description: Measured by flow cytometry and/or luciferase assays
Measure: Magnitude of serum Antibody-dependent cellular cytotoxicity (ADCC) Time: Measured at week 56Description: Measured by flow cytometry
Measure: Response rate of serum Antibody-dependent cellular phagocytosis (ADCP) Time: Measured at week 56Description: Measured by flow cytometry
Measure: Magnitude of serum Antibody-dependent cellular phagocytosis (ADCP) Time: Measured at week 56This is an open-label, single-sequence, multiple-dose, 3 cohort study to investigate the effects of DRV/RTV and/or ETR on the pharmacokinetics (PK) of GSK3640254 and the effects of GSK3640254 on the PK of DRV/RTV and/or ETR. This study will aid in understanding these interactions and resulting changes in exposure (if any) when given in combination with GSK3640254.
Description: Blood samples will be collected for the concentrations of GSK3640254.
Measure: Cohorts 1, 2 and 3: Area under the plasma concentration-time curve from time zero to the end of the dosing interval at steady state (AUC[0-tau]) of GSK3640254 Time: Up to Day 36Description: Blood samples will be collected for the concentrations of GSK3640254.
Measure: Cohorts 1, 2 and 3: Maximum observed concentration (Cmax) of GSK3640254 Time: Up to Day 36Description: Blood samples will be collected for the concentrations of DRV.
Measure: Cohort 1: AUC(0-tau) of DRV after co-administration with GSK3640254 Time: Up to Day 35Description: Blood samples will be collected for the concentrations of DRV.
Measure: Cohort 1: Cmax of DRV after co-administration with GSK3640254 Time: Up to Day 35Description: Blood samples will be collected for the concentrations of RTV.
Measure: Cohort 1: AUC(0-tau) of RTV after co-administration with GSK3640254 Time: Up to Day 35Description: Blood samples will be collected for the concentrations of RTV.
Measure: Cohort 1: Cmax of RTV after co-administration with GSK3640254 Time: Up to Day 35Description: Blood samples will be collected for the concentrations of ETR.
Measure: Cohort 2: AUC(0-tau) of ETR after co-administration with GSK3640254 Time: Up to Day 36Description: Blood samples will be collected for the concentrations of ETR.
Measure: Cohort 2: Cmax of ETR after co-administration with GSK3640254 Time: Up to Day 36Description: Blood samples will be collected for the concentrations of GSK3640254.
Measure: Cohorts 1 and 2: Time of maximum observed concentration (Tmax) of GSK3640254 Time: Up to Day 36Description: Blood samples will be collected for the concentrations of GSK3640254.
Measure: Cohorts 1 and 2: Plasma concentration at the end of the dosing interval (Ctau) of GSK3640254 Time: Up to Day 36Description: Blood samples will be collected for the concentrations of DRV.
Measure: Cohort 1: Tmax of DRV Time: Up to Day 35Description: Blood samples will be collected for the concentrations of DRV.
Measure: Cohort 1: Ctau of DRV Time: Up to Day 35Description: Blood samples will be collected for the concentrations of RTV.
Measure: Cohort 1: Tmax of RTV Time: Up to Day 35Description: Blood samples will be collected for the concentrations of RTV.
Measure: Cohort 1: Ctau of RTV Time: Up to Day 35Description: Blood samples will be collected for the concentrations of ETR.
Measure: Cohort 2: Tmax of ETR Time: Up to Day 36Description: Blood samples will be collected for the concentrations of ETR.
Measure: Cohort 2: Ctau of ETR Time: Up to Day 36Description: All AEs, SAEs and AEs leading to discontinuation and deaths will be assessed.
Measure: Cohorts 1, 2 and 3: Number of participants with adverse events (AEs), serious AEs (SAEs) and AEs leading to discontinuation and deaths Time: Up to Day 36Description: Blood samples will be collected for the assessment of hematology and chemistry parameters.
Measure: Cohorts 1, 2 and 3: Number of participants with abnormal laboratory parameters Time: Up to Day 36Description: Urine samples will be collected for the assessment of urinalysis parameters.
Measure: Cohorts 1, 2 and 3 : Number of participants with abnormal urinalysis parameters Time: Up to Day 36Description: Number of participants with abnormal vital signs will be assessed.
Measure: Cohorts 1, 2 and 3: Number of participants with abnormal vital signs Time: Up to Day 36Description: Number of participants with abnormal ECG parameters will be assessed.
Measure: Cohorts 1, 2 and 3: Number of participants with abnormal electrocardiogram (ECG) parameters Time: Up to Day 36Alphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on December 13, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
Drug Reports MeSH Reports HPO Reports