CovidResearchTrials by Shray Alag

CovidResearchTrials Covid 19 Research using Clinical Trials (Home Page)

Report for D015658: HIV Infections NIH

(Synonyms: HIV In, HIV Inf, HIV Infe, HIV Infec, HIV Infect, HIV Infecti, HIV Infectio, HIV Infection, HIV Infections)

Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (35)

Name (Synonyms) Correlation
drug109 ATV Wiki 0.32
drug595 Cabotegravir 400 mg/mL Wiki 0.32
drug13 10% Povidone-iodine nasal decolonization swab plus 0.12% CHG oral rinse Wiki 0.32
drug1158 GSK3640254 200 mg Wiki 0.32
drug594 Cabotegravir 200 mg/mL Wiki 0.32
drug3159 [14C]-GSK3640254 intravenous infusion Wiki 0.32
drug1079 FTC/TAF Wiki 0.32
drug4 0.12% Chlorhexidine oral/nasal rinse Wiki 0.32
drug1750 Midazolam 5 mg (2.5 mL) Wiki 0.32
drug49 50 mg/mL Virazole Wiki 0.32
drug2212 Pravastatin 40 mg Wiki 0.32
drug1967 Omeprazole 40 mg Wiki 0.32
drug913 Dolutegravir Wiki 0.32
drug597 Caffeine 200 mg Wiki 0.32
drug3160 [14C]-GSK3640254 powder Wiki 0.32
drug898 Digoxin 0.25 mg Wiki 0.32
drug1745 Metoprolol 100 mg Wiki 0.32
drug1123 Flurbiprofen 100 mg Wiki 0.32
drug14 100 mg/mL Virazole Wiki 0.32
drug2520 SKILLZ-Girl Enhanced football curriculum Wiki 0.32
drug596 Cabotegravir sodium (Oral Lead In) Wiki 0.32
drug1157 GSK3640254 Wiki 0.32
drug1159 GSK3640254 Oral tablet Wiki 0.32
drug1779 Montelukast 10 mg Wiki 0.32
drug6 0.5% Povidone/Iodine oral/nasal rinse Wiki 0.32
drug695 Cobicistat Wiki 0.32
drug362 BR Wiki 0.32
drug2814 TERA Intervention Wiki 0.32
drug1160 GSK3739937 Wiki 0.32
drug822 DRV Wiki 0.32
drug2545 Saline oral/nasal rinse Wiki 0.32
drug58 ABC/3TC Wiki 0.32
drug1887 No intervention Wiki 0.07
drug2698 Standard of Care Wiki 0.06
drug2122 Placebo Wiki 0.03

Correlated MeSH Terms (6)

Name (Synonyms) Correlation
D000163 Acquired Immunodeficiency Syndrome NIH 0.55
D007153 Immunologic Deficiency Syndromes NIH 0.13
D003141 Communicable Diseases NIH 0.02
D007239 Infection NIH 0.02
D045169 Severe Acute Respiratory Syndrome NIH 0.02
D018352 Coronavirus Infections NIH 0.01

Correlated HPO Terms (1)

Name (Synonyms) Correlation
HP:0002721 Immunodeficiency HPO 0.13

There are 10 clinical trials

Clinical Trials

1 A Phase 2/3, Multicenter, Open-label, Multicohort Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected, Virologically Suppressed Pediatric Participants

Cohort 1: The primary objectives are: - To evaluate the steady-state pharmacokinetics (PK) of Atazanavir (ATV) and Darunavir (DRV) and confirm the dose of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) in HIV-1 infected, virologically suppressed adolescent participants weighing ≥ 25 kg (12 to < 18 years of age) - To evaluate the safety and tolerability of ATV/co or DRV/co through 24 weeks in HIV-1 infected, virologically suppressed adolescent participants weighing ≥ 25 kg (12 to < 18 years of age) Cohort 2: The primary objectives are: - To evaluate the steady-state PK of ATV and DRV and confirm the dose of ATV/co or DRV/co in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age) - To evaluate the steady-state PK of tenofovir alafenamide (TAF) and confirm the dose of emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age) - To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age) Cohort 3: The primary objectives are: - To evaluate the steady-state PK of ATV and DRV and confirm the dose of ATV/co or DRV/co in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age) - To evaluate the steady-state PK of TAF and confirm the dose of F/TAF in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age) - To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)

NCT02016924 Acquired Immune Deficiency Syndrome (AIDS) HIV Infections Drug: ATV Drug: DRV Drug: Cobicistat Drug: BR
MeSH:HIV Infections Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndromes
HPO:Immunodeficiency

Primary Outcomes

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Measure: Pharmacokinetic (PK) Parameter: AUCtau of ATV and DRV

Time: Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Measure: Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, and TAF for Cohorts 2 and 3

Time: Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4

Measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Treatment Emergent Laboratory Abnormalities Through Week 24

Time: First dose date and up to 24 weeks plus 30 days

Secondary Outcomes

Description: Ctau is defined as the observed drug concentration at the end of the dosing interval.

Measure: PK Parameter: Ctau of ATV, DRV, and COBI for Cohort 1

Time: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).

Description: Cmax is defined as the maximum observed concentration of drug.

Measure: PK Parameter: Cmax of ATV, DRV, and COBI for Cohort 1

Time: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).

Description: CL/F is defined as the apparent oral clearance following administration of the drug.

Measure: PK Parameter: CL/F of ATV, DRV, and COBI for Cohort 1

Time: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).

Description: Vz/F is defined as the apparent volume of distribution of the drug.

Measure: PK Parameter: Vz/F of COBI for Cohort 1

Time: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).

Description: Ctau is defined as the observed drug concentration at the end of the dosing interval.

Measure: PK Parameter: Ctau of ATV, DRV, COBI, FTC, and TFV for Cohorts 2 and 3

Time: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48

Description: Cmax is defined as the maximum observed concentration of drug.

Measure: PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV for Cohorts 2 and 3

Time: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48

Description: CL/F is defined as the apparent oral clearance following administration of the drug.

Measure: PK Parameter: CL/F of ATV, DRV, and TAF for Cohorts 2 and 3

Time: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48

Description: Vz/F is defined as the apparent volume of distribution of the drug.

Measure: PK Parameter: Vz/F of COBI and TAF for Cohorts 2 and 3

Time: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48

Measure: The incidence of treatment-emergent AEs and treatment-emergent laboratory abnormalities through Week 48

Time: Up to 48 weeks plus 30 days

Measure: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 and as defined by the US FDA-defined snapshot algorithm

Time: Week 24

Measure: The change from baseline in CD4+ cell counts

Time: Week 24

Measure: The change from baseline in CD4+ cell counts

Time: Week 48

Measure: The change from baseline in CD4+ percentages

Time: Week 24

Measure: The change from baseline in CD4+ percentages

Time: Week 48

Measure: Acceptability of COBI and F/TAF as Measured by Palatability

Time: Day 1, and at Weeks 4 (Day 10 for Cohort 1 Part A), 24 and 48.

2 Triggered Escalating Real-time Adherence Intervention to Promote Rapid HIV Viral Suppression Among Youth Living With HIV Failing Antiretroviral Therapy: The TERA Study

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.

NCT03292432 HIV Infections Behavioral: TERA Intervention Behavioral: Standard of Care
MeSH:HIV Infections

Primary Outcomes

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 enrollment

Description: 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 enrollment

Secondary Outcomes

Description: 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 enrollment

Description: 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 enrollment

Description: 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 enrollment

Description: 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 weeks

Description: 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 weeks

Description: 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 weeks

3 Prospective Observational Study for Patients With HIV and Confirmed SARS-CoV-2

Currently, 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.

NCT04333953 HIV/AIDS COVID-19 SARS-CoV-2 Other: No intervention
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

Primary Outcomes

Description: COVID-19 related death among patients with HIV and COVID-19

Measure: Mortality

Time: 30 days

Secondary Outcomes

Description: Percentage of patients who required hospitalization

Measure: Frequency of patients requiring hospital admissions

Time: 30 days

Description: Percentage of patients who required ICU admission

Measure: Frequency of patients requiring ICU admissions

Time: 30 days

Description: Percentage of patients who required respiratory support (new oxygen use, non-invasive ventilation,or invasive ventilation)

Measure: Frequency of respiratory support use

Time: 30 days

Description: 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 days

Description: Percentage of patients who developed liver injury defined as increase in baseline ALT

Measure: Frequency of liver injury

Time: 30 days

4 COVID-19 in People Living With HIV: Evaluation of Risk Factors and Outcomes in Resource-limited Settings. A Pooled Substudy of ADVANCE, D²EFT, DolPHIN2 and NAMSAL

COHIVE 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.

NCT04371835 HIV-infection/Aids Coronavirus Infection
MeSH:Infection Communicable Diseases HIV Infections Coronavirus Infections Severe Acute Respiratory Syndrome Acquired Immunodeficiency Syndrome

Primary Outcomes

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 baseline

Description: 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 28

Description: 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 3

Secondary Outcomes

Description: 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 year

5 Effects of GSK3640254 on the Single-Dose Pharmacokinetics of Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin) in Healthy Subjects

This 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.

NCT04425902 HIV Infections Drug: GSK3640254 200 mg Drug: Caffeine 200 mg Drug: Metoprolol 100 mg Drug: Montelukast 10 mg Drug: Flurbiprofen 100 mg Drug: Omeprazole 40 mg Drug: Midazolam 5 mg (2.5 mL) Drug: Digoxin 0.25 mg Drug: Pravastatin 40 mg
MeSH:HIV Infections

Primary Outcomes

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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.

Measure: Cmax for metoprolol

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of metoprolol.

Measure: Tmax for metoprolol

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.

Measure: Cmax for montelukast

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of montelukast.

Measure: Tmax for montelukast

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.

Measure: Cmax for flurbiprofen

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.

Measure: Tmax for flurbiprofen

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.

Measure: Cmax for omeprazole

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of omeprazole.

Measure: Tmax for omeprazole

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.

Measure: Cmax for midazolam

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of midazolam.

Measure: Tmax for midazolam

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.

Measure: Cmax for digoxin

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of digoxin.

Measure: Tmax for digoxin

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.

Measure: Cmax for pravastatin

Time: Day 1 to Day 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of pravastatin.

Measure: Tmax for pravastatin

Time: Day 1 to Day 26

Description: 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 26

Secondary Outcomes

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected for the assessment of hematology parameters.

Measure: Absolute values of absolute neutrophil count

Time: Day 1 to Day 26

Description: Blood samples will be collected for the assessment of hematology parameters.

Measure: Absolute values of hematocrit

Time: Day 1 to Day 26

Description: Blood samples will be collected for the assessment of hematology parameters.

Measure: Absolute values of hemoglobin (Hgb)

Time: Day 1 to Day 26

Description: 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 26

Description: Blood samples will be collected for the assessment of hematology parameters.

Measure: Absolute values of Mean corpuscular volume (MCV)

Time: Day 1 to Day 26

Description: Blood samples will be collected for the assessment of hematology parameters.

Measure: Absolute values of Mean corpuscular hemoglobin (MCH)

Time: Day 1 to Day 26

Description: 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 26

Description: Blood samples will be collected for the assessment of clinical chemistry parameters.

Measure: Absolute values of anion gap

Time: Day 1 to Day 26

Description: Blood samples will be collected for the assessment of clinical chemistry parameters.

Measure: Absolute values of total cholesterol

Time: Day 1 to Day 26

Description: Blood samples will be collected for the assessment of clinical chemistry parameters.

Measure: Absolute values of triglycerides

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Urine samples will be collected for the assessment of urine parameters.

Measure: Absolute values of urine specific gravity

Time: Day 1 to Day 26

Description: 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 26

Description: Urine samples will be collected for the assessment of urine parameters.

Measure: Absolute values of urine glucose

Time: Day 1 to Day 26

Description: Urine samples will be collected for the assessment of urine parameters.

Measure: Absolute values of urine protein

Time: Day 1 to Day 26

Description: Urine samples will be collected for the assessment of urine parameters.

Measure: Absolute values of urine blood

Time: Day 1 to Day 26

Description: Urine samples will be collected for the assessment of urine parameters.

Measure: Absolute values of urine ketones

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Temperature will be assessed using an automated device.

Measure: Absolute values of oral temperature

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Oxygen saturation of participants will be assessed using pulse oximetry.

Measure: Absolute values of oxygen saturation

Time: Day 1 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254

Measure: Cmax for GSK3640254

Time: Day 11 to Day 26

Description: 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 26

Description: Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254

Measure: Tmax for GSK3640254

Time: Day 11 to Day 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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 26

Description: 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

6 Reaching 90 90 90 in Adolescents in Zambia: Using All Our SKILLZ

"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.

NCT04429061 HIV Infections Pregnancy Related STI Mental Health Wellness 1 Behavioral: SKILLZ-Girl Enhanced football curriculum
MeSH:HIV Infections

Primary Outcomes

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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

7 A Phase 1, Two-part, Double-blind, Active-control, Randomized Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat-Dose Cabotegravir (CAB 400 mg/mL Formulation) Long-Acting Injection Following Subcutaneous or Intramuscular Administration in Healthy Adult Participants

This 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.

NCT04484337 HIV Infections Drug: Cabotegravir sodium (Oral Lead In) Drug: Cabotegravir 400 mg/mL Drug: Cabotegravir 200 mg/mL
MeSH:HIV Infections

Primary Outcomes

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 22

Description: 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 52

Description: 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 10

Description: 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 64

Description: 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 22

Description: 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 52

Description: 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 10

Description: 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 64

Description: 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 22

Description: 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 52

Description: 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 10

Description: 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 64

Description: 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 22

Description: 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 52

Description: 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 10

Description: 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 64

Description: 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 52

Description: 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 64

Description: 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 52

Description: 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 64

Description: 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 4

Description: 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 12

Description: 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 8

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 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)

Secondary Outcomes

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 injection

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 AEs (Part 2)

Time: Up to 52 weeks post last injection

Description: 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 injection

Description: 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 injection

Description: Participants with liver biochemistry abnormalities will be assessed.

Measure: Number of participants with liver biochemistry abnormalities

Time: Up to 52 weeks post last injection

8 A Phase IIb, Randomized, Partially Blind, Active Controlled, Dose-range Finding Study of GSK3640254 Compared to a Reference Arm of Dolutegravir, Each in Combination With Nucleoside Reverse Transcriptase Inhibitors, in HIV-1 Infected Antiretroviral Treatment-naive Adults

Infection 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. The total study duration will be approximately 7 years.

NCT04493216 HIV Infections Drug: GSK3640254 Drug: ABC/3TC Drug: FTC/TAF Drug: Dolutegravir Drug: Placebo
MeSH:HIV Infections

Primary Outcomes

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 24

Secondary Outcomes

Description: 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 96

Description: 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 96

Description: 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 96

Description: Absolute values of CD4+ cells at Weeks 24, 48, and 96 will be assessed.

Measure: Absolute values of CD4+ T-cell counts at Weeks 24, 48 and 96

Time: At Weeks 24, 48 and 96

Description: Change from Baseline in CD4+ cells at Weeks 24, 48 and 96 will be assessed.

Measure: Change from Baseline in CD4+ T-cell counts at Weeks 24, 48 and 96

Time: Baseline and Weeks 24, 48 and 96

Description: An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose; results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability or incapacity or is a congenital anomaly or birth defect or any other situation that require medical or scientific judgment. Number of participants with SAEs, death and AEs leading to treatment discontinuation will be assessed at Weeks 24, 48 and 96.

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 96

Description: An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants with AEs will be assessed at Weeks 24, 48 and 98.

Measure: Number of participants with AEs at Weeks 24, 48 and 96

Time: At Weeks 24, 48 and 96

Description: An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Severity of AEs will be assessed at Weeks 24, 48 and 96.

Measure: Severity of AEs at Weeks 24, 48 and 96

Time: At Weeks 24, 48 and 96

Description: 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 96

Description: 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 96

Description: 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 96

Description: 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 24

Description: 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 48

Description: 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 24

Description: 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 48

Description: 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 24

Description: 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 48

9 A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3739937 in Healthy Participants

Human 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.

NCT04493684 HIV Infections Drug: GSK3739937 Drug: Placebo
MeSH:HIV Infections

Primary Outcomes

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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

Description: 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 44

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 2: Cohort 3-4: Number of Participants With AEs and SAEs

Time: Up to Day 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

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 2: Cohort 5: Number of Participants With AEs and SAEs

Time: Up to Day 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Description: 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 42

Secondary Outcomes

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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-dose

Description: 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 14

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 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 14

Description: 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 14

Description: 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 14

Description: 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 14

Description: 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 14

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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 28

Description: 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-dose

Description: 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-dose

Description: 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 14

Description: 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 28

Description: 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 14

Description: 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 28

Description: 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 14

Description: 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 28

Description: 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-dose

Description: 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 14

Description: 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 28

Description: 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 14

Description: 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 28

Description: 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 14

Description: 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 28

Description: 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 14

Description: 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 28

10 A Two-period Study in Healthy Male Participants to Determine the Pharmacokinetics, Balance/Excretion, and Metabolism of [14C]-GSK3640254 Following a Single Intravenous Radiolabeled Microtracer Dose (Concomitant With a Non-radiolabeled Oral Dose) and a Single Oral Radiolabeled Dose

This 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.

NCT04507321 HIV Infections Drug: GSK3640254 Oral tablet Drug: [14C]-GSK3640254 intravenous infusion Drug: [14C]-GSK3640254 powder
MeSH:HIV Infections

Primary Outcomes

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-dose

Description: 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 Hours

Description: 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 Hours

Description: 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 Hours

Description: 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 Hours

Description: 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.

Secondary Outcomes

Description: AEs and SAEs will be collected.

Measure: Number of participants With Adverse Events (AEs) and Serious AEs (SAEs)

Time: Up to 50 days

Description: 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 days

Description: 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 days

Description: Number of participants with abnormal vital signs will be assessed.

Measure: Number of participants with abnormal vital signs

Time: Up to 50 days

Description: 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 Hours

HPO Nodes