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. Geometric least‐squares mean ratios and 90% confidence intervals were obtained using linear mixed‐effects models. Adverse events (AEs) were monitored. Results: Of 20 participants enrolled, 19 completed the study. Plasma concentrations of all cocktail substrates were generally similar with or without GSK'254 co‐administration. All 90% confidence intervals around geometric least‐squares mean ratios for cocktail substrate PK parameters indicated no to weak interactions. Steady‐state plasma GSK'254 concentrations were achieved by Day 17 and maintained through Day 21. Nine participants (45%) reported 17 AEs; most (88%) were grade 1. Two grade 2 treatment‐related AEs (maculopapular rash [leading to withdrawal] and papular rash) were reported during GSK'254 administration alone. Conclusions: Co‐administration of GSK'254 with a metabolic probe cocktail in healthy participants indicated very low risk of clinically relevant effect on PK of any substrates or associated metabolites. No new safety/tolerability concerns were identified. These results support ongoing phase IIb and planned phase III studies of GSK'254 in people living with HIV‐1. [ABSTRACT FROM AUTHOR]