Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants. Issue 5 (7th January 2022)

• Record Type: Journal Article
• Authors: Johnson, Mark; Pene Dumitrescu, Teodora; Joshi, Samit R.; Mathew, Ashwin; Bainbridge, Veronica; Zhan, Joyce; Lataillade, Max
• Is Part Of: Clinical pharmacology in drug development. Volume 11:Issue 5(2022)
• Page Start: 632
• Page End: 639
• Publication Date: 2022-01-07
• Subjects: food effect -- GSK3640254 -- maturation inhibitor -- pharmacokinetics -- relative bioavailability; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.1051
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: 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). Overall, 39 participants were randomized to treatment (part 1, n = 18; part 2, n = 21). All participants in part 1 completed the study; 2 participants in part 2 withdrew before study completion (adverse event, n = 1; physician decision, n = 1). In part 1, plasma exposures of the GSK3640254 tablet formulation were not meaningfully different from those of the capsule formulation when administered in the presence of a moderate‐fat meal. In part 2, GSK3640254 plasma exposures increased by ≈3‐ to 4‐fold under high‐ and moderate‐fat conditions, respectively, compared with fasted conditions. No major safety or tolerability findings were observed. The highest incidence of adverse events (24%) was reported under high‐fat conditions. Taken together, these data support the use of the tablet formulation coadministered with food in the clinical development of GSK3640254 for treatment of HIV‐1.