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| Name (Synonyms) | Correlation | |
|---|---|---|
| drug1496 | FTC/TAF Wiki | 0.71 |
| drug1253 | Dolutegravir Wiki | 0.71 |
| drug82 | ABC/3TC Wiki | 0.71 |
| Name (Synonyms) | Correlation |
|---|
Navigate: Correlations HPO
There are 2 clinical trials
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. In the experimental arms, GSK3640254 will be administered in 3 blinded doses until the last participant completes their Week 48 study visit (Week 48 Secondary Endpoint study milestone). Thereafter, participants whose most recent HIV-1 ribonucleic acid (RNA) less than (<)50 copies/milliliters (c/mL) in the GSK3640254 arms will move into the Non-Randomised Phase and will be switched from their blinded dose to the open label optimal dose. Simultaneously, these participants will also be switched from their dual NRTI therapy to DTG. The total study duration will be approximately 7 years.
Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Week 24.
Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24 Time: At Week 24Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Weeks 48 and 96.
Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Weeks 48 and 96 Time: At Weeks 48 and 96Description: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.
Measure: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Change from Baseline in level of plasma HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.
Measure: Change from Baseline in plasma HIV-1 RNA at Weeks 24, 48 and 96 (c/mL) Time: Baseline and Weeks 24, 48 and 96Description: Absolute values of CD4+ cells at Weeks 24, 48, and 96 will be assessed.
Measure: Absolute values of CD4+ cell counts at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Change from Baseline in CD4+ cells at Weeks 24, 48 and 96 will be assessed.
Measure: Change from Baseline in CD4+ cell counts at Weeks 24, 48 and 96 (Cells per cubic millimeters [cells/mm^3]) Time: Baseline and Weeks 24, 48 and 96Description: All SAEs, deaths and AEs leading to treatment discontinuation will be assessed.
Measure: Number of participants with serious adverse events (SAEs), Deaths and adverse events (AEs) leading to treatment discontinuation at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: All AEs will be assessed.
Measure: Number of participants with AEs at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Severity of AEs will be assessed.
Measure: Severity of AEs at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Number of participants with AEs in GI, Psych/CNS will be assessed at Weeks 24, 48 and 96.
Measure: Number of participants with AEs in Gastrointestinal (GI), Psychological (Psych)/Central nervous system (CNS) at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Plasma samples will be collected for analyzing phenotypic resistance at Weeks 24, 48 and 96 using PhenoSense genotype testing (GT) for reverse transcriptase (RT) (NRTI and non-nucleoside reverse transcriptase inhibitors [NNRTI]) and Protease inhibitor (PI), PhenoSense Integrase, PhenoSense Gag assays for GSK3640254.
Measure: Number of participants who develop phenotypic resistance at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Plasma samples will be collected for analyzing genotypic resistance at Weeks 24, 48 and 96 using PhenoSense GT for RT and Protease genotype, GeneSeq Integrase, and Gag genotype (using a Next Generation Sequencing platform).
Measure: Number of participants who develop genotypic resistance at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: Maximum observed concentration (Cmax) of GSK3640254 at steady state at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: Cmax of GSK3640254 at steady state at Week 48 Time: At Week 48Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: AUC over the dosing interval (AUC [0-tau]) of GSK3640254 at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: AUC (0-tau) of GSK3640254 at steady state at Week 48 Time: At Week 48Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: Plasma concentration at the end of the dosing (Ctau) of GSK3640254 at steady state at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: Ctau of GSK3640254 at steady state at Week 48 Time: At Week 48This study will aim to evaluate the effect of therapeutic and supratherapeutic oral doses of GSK3640254 on cardiac conduction compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. The study has 2 parts: Part 1 will determine the supratherapeutic dose for Part 2, which will be the main corrected QT interval (QTc) study. Part 1 consists of 2 sequential cohorts: Sentinel Cohort 1 will evaluate once daily (QD) dosing of GSK3640254 or placebo for 7 days and Sentinel Cohort 2 will evaluate twice daily (BID) dosing of GSK3640254 or placebo for 7 days. Part 2 will investigate the safety, tolerability and Pharmacokinetics (PK) of GSK3640254 doses on cardiac conduction as compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. Moxifloxacin will be included as a positive control. All doses of study intervention will be administered under fed conditions and will receive a moderate-fat meal 30 minutes prior to dosing. The total duration of the study is approximately 91 days. Approximately 58 participants will be enrolled in the study.
Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Area under the plasma concentration-time curve from time zero to time t (AUC[0-t]) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: AUC from time zero to the end of the dosing interval at steady state (AUC[0-tau]) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Maximum observed concentration (Cmax) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Plasma concentration at the end of the dosing interval (Ctau) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 1: Time of maximum observed concentration (Tmax) of GSK3640254 Time: Up to Day 9 of each cohortDescription: Blood samples will be collected for measurement of plasma concentrations of GSK3640254 and its major metabolite.
Measure: Part 1: Plasma concentrations of GSK3640254 and its major metabolite Time: Up to Day 9 of each cohortDescription: All AEs and SAEs will be assessed.
Measure: Part 1: Number of participants with adverse events (AEs) and serious AEs (SAEs) Time: Up to Day 9 of each cohortDescription: Blood samples will be collected for the assessment of hematology and chemistry parameters.
Measure: Part 1: Number of participants with abnormal laboratory parameters Time: Up to Day 9 of each cohortDescription: Urine samples will be collected for the assessment of urinalysis parameters.
Measure: Part 1: Number of participants with abnormal urinalysis parameters Time: Up to Day 9 of each cohortDescription: Number of participants with abnormal ECG parameters will be assessed.
Measure: Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters Time: Up to Day 9 of each cohortDescription: Number of participants with abnormal vital signs will be assessed.
Measure: Part 1: Number of participants with abnormal vital signs Time: Up to Day 9 of each cohortDescription: Placebo-corrected change from Baseline in QTcF will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in QT interval corrected for heart rate using Fridericia's formula (QTcF) following administration of GSK3640254 (Milliseconds [ms]) Time: Baseline (Day -1) and up to Day 51Description: Blood samples will be collected for measurement of plasma concentrations of GSK3640254 and its major metabolite.
Measure: Part 2: Plasma concentrations of GSK3640254 and its major metabolite Time: Up to Day 51Description: Change from Baseline in heart rate will be analyzed.
Measure: Part 2: Change from Baseline in heart rate (HR) (Beats per minute [bpm]) Time: Baseline (Day -1) and up to Day 51Description: Change from Baseline in QTcF, PR interval and QRS interval will be analyzed.
Measure: Part 2: Change from Baseline in QTcF, PR interval and QRS interval (ms) Time: Baseline (Day -1) and up to Day 51Description: Placebo-corrected change from Baseline in HR will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in HR (bpm) Time: Baseline (Day -1) and up to Day 51Description: Placebo-corrected change from Baseline in QTcF, PR interval and QRS interval will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in QTcF, PR interval and QRS interval (ms) Time: Baseline (Day -1) and up to Day 51Description: Number of participants with abnormal HR, QTcF, PR interval and QRS interval will be assessed.
Measure: Part 2: Number of participants with abnormal HR, QTcF, PR interval and QRS interval Time: Up to Day 51Description: Number of participants with treatment emergent changes of T-wave morphology will be evaluated.
Measure: Part 2: Number of participants with treatment emergent changes of T-wave morphology Time: Up to Day 51Description: Number of participants with presence of U-wave will be evaluated.
Measure: Part 2: Number of participants with presence of U-wave Time: Up to Day 51Description: Placebo-corrected change from Baseline in QTcF will be analyzed.
Measure: Part 2: Placebo-corrected change from Baseline in QTcF following administration of Moxifloxacin (ms) Time: Baseline (Day -1) and up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: AUC(0-t) of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: AUC(0-tau) of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: Cmax of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: Ctau of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.
Measure: Part 2: Tmax of GSK3640254 Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of Moxifloxacin.
Measure: Part 2: Cmax of Moxifloxacin Time: Up to Day 51Description: Blood samples will be collected at the indicated time points for PK analysis of Moxifloxacin.
Measure: Part 2: Tmax of Moxifloxacin Time: Up to Day 51Description: All AEs and SAEs will be assessed.
Measure: Part 2: Number of participants with AEs and SAEs Time: Up to Day 51Description: Blood samples will be collected for the assessment of hematology and chemistry parameters.
Measure: Part 2: Number of participants with abnormal laboratory parameters Time: Up to Day 51Description: Urine samples will be collected for the assessment of urinalysis parameters.
Measure: Part 2: Number of participants with abnormal urinalysis parameters Time: Up to Day 51Description: Number of participants with abnormal ECG parameters will be assessed.
Measure: Part 2: Number of participants with abnormal ECG parameters Time: Up to Day 51Description: Number of participants with abnormal vital signs will be assessed.
Measure: Part 2: Number of participants with abnormal vital signs Time: Up to Day 51Alphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on September 26, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
Drug Reports MeSH Reports HPO Reports