Effects of the HIV-1 maturation inhibitor GSK3640254 on QT interval in healthy participants.

GSK3640254 (GSK'254) is a novel HIV-1 maturation inhibitor with pharmacokinetics supporting once-daily (QD) therapy for HIV-1 treatment. This thorough QT/corrected QT (QTc) study evaluated the effect of GSK'254 on cardiac repolarization. In this two-part, randomized study, healthy participants received GSK'254 or placebo QD for 7 days (part 1) to determine safety and pharmacokinetics of a 500-mg supratherapeutic dose.

Pharmacokinetics and tolerability of the maturation inhibitor GSK3640254 coadministered with darunavir/ritonavir and/or etravirine in healthy adults.

Aims: This phase I study investigated potential drug-drug interactions of the maturation inhibitor GSK3640254 (GSK'254) with darunavir/ritonavir (DRV/RTV) and/or etravirine (ETR).

Methods: In this randomized, open-label, single-sequence, multiple-dose study, healthy participants received GSK'254 200 mg once daily alone or coadministered with DRV/RTV 600/100 mg twice daily (BID; n = 19), ETR 200 mg BID (n = 19) or DRV/RTV 600/100 mg + ETR 200 mg BID (n = 16) under fed conditions. Primary endpoints were steady-state area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC ) and maximum observed concentration (C ).

Open-label, drug-drug interaction study between the HIV-1 maturation inhibitor GSK3640254 and a metabolic probe cocktail in healthy participants.

Aims: GSK3640254 (GSK'254) is an HIV-1 maturation inhibitor with pharmacokinetics (PK) supporting once-daily dosing. GSK'254 will be co-administered with cytochrome P450 enzyme substrates and drug transporters, including other antiretrovirals, in people living with HIV-1 (PLWH).

Methods: In this open-label study, healthy participants received a single dose of a cocktail of eight cytochrome P450 and transporter probe substrates on Day 1, followed by a 10-day washout before receiving GSK'254 200 mg once daily from Days 11 to 20 and a single dose of cocktail + GSK'254 200 mg on Day 21.

Investigation of Clinical Absorption, Distribution, Metabolism, and Excretion and Pharmacokinetics of the HIV-1 Maturation Inhibitor GSK3640254 Using an Intravenous Microtracer Combined with EnteroTracker for Biliary Sampling.

GSK3640254 is a next-generation maturation inhibitor in development for HIV-1 treatment, with pharmacokinetics (PK) supporting once-daily oral dosing in human. This open-label, nonrandomized, two-period clinical mass balance and excretion study was used to investigate the excretion balance, PK, and metabolism of GSK3640254. Five healthy men received a single intravenous microtracer of 100 g [C]GSK3640254 with a concomitant oral nonradiolabeled 200-mg tablet followed by an oral 85-mg dose of [C]GSK3640254 14 days later.

Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254.

Background: GSK3640254 (GSK'254) is a next-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor with pharmacokinetics (PK) supporting once-daily therapy.

Methods: This phase IIa double-blind (sponsor-unblinded), randomized, placebo-controlled, adaptive study evaluated antiviral effect, safety, tolerability, and PK of once-daily GSK'254 monotherapy administered with food (moderate-fat meal) in HIV-1-positive, treatment-naive adults. In part 1, participants received GSK'254 10 or 200 mg for 10 days.

Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants.

GSK3640254 is a next-generation maturation inhibitor with demonstrated potency across HIV-1 subtypes and a high barrier to emergent resistance. This phase I, 2-part, randomized, open-label study (ClinicalTrials.gov identifier, NCT04263142) in healthy participants assessed the relative bioavailability of a single dose of GSK3640254 200 mg in tablet and capsule formulations (part 1) and the effect of food on the pharmacokinetic profile of the tablet formulation (part 2).

A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants.

GSK3640254 is a next-generation maturation inhibitor that would likely be combined with standard antiretroviral agents to form a regimen of ≥2 fully active classes. This phase I, open-label, 2-period, 1-way study assessed potential pharmacokinetic (PK) interactions between GSK3640254 and tenofovir alafenamide/emtricitabine (TAF/FTC; including the metabolite tenofovir [TFV]) in healthy volunteers. Eligible participants received TAF/FTC 25/200 mg once daily (QD) on days 1 through 21 with a moderate-fat meal; GSK3640254 200 mg QD was added on days 15 through 21.

Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor.

Despite advances in HIV-1 management with antiretroviral therapy, drug resistance and toxicities with multidrug regimens can result in treatment failure. Hence, there is a continuing demand for antiretroviral agents (ARVs) with novel mechanisms of action. Maturation inhibitors inhibit HIV-1 replication via a unique mechanism of action and can be combined with other ARVs.