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

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.

Keywords: GSK3640254; food effect; maturation inhibitor; pharmacokinetics; relative bioavailability.

Conflict of interest statement

M.J., S.R.J., and M.L. are employees of ViiV Healthcare and may own stock in GlaxoSmithKline (GSK). A.M., V.B., and J.Z. are employees of and may own stock in GSK. T.P.D. was an employee of GSK during the conduct of the study and may own stock in GSK.

© 2022 ViiV Healthcare. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.

Figures

Figure 1

Structure of GSK3640254.

Figure 2

Study design schematics for (A) part 1 and (B) part 2.

Figure 3

Mean (SD) GSK3640254 plasma concentration–time plots by treatment in part 1: (A) linear and (B) semilogarithmic. Dashed line represents lower limit of quantification (3.00 ng/mL). SE, standard error.

Figure 4

Mean (SD) GSK3640254 plasma concentration–time plots by treatment in part 2: (A) linear and (B) semilogarithmic. Dashed line represents lower limit of quantification (3.00 ng/mL).