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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.

SUBMITTER: Johnson M

PROVIDER: S-EPMC9306620 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Johnson Mark M Pene Dumitrescu Teodora T Joshi Samit R SR Mathew Ashwin A Bainbridge Veronica V Zhan Joyce J Lataillade Max M

Clinical pharmacology in drug development 20220107 5

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 w ...[more]

PMID: 34995417

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Project description:IntroductionUlotaront (SEP-363856), a dual trace animeassociated receptor 1 (TAAR1) and 5-HT1A receptor agonist, is in phase 3 clinical development for the treatment of schizophrenia. This study evaluated the comparative bioequivalence (BE) between tablet and capsule formulations of ulotaront and the food effect (FE) on pharmacokinetics (PK) of tablet form in healthy adult human subjects.MethodsThe BE study applied an open-label two-period crossover design in 24 healthy volunteers. Subjects were randomly assigned (1:1) to dosing sequence AB or BA (A, 25 mg ulotaront tablet; B, 25 mg ulotaront capsule). The FE study also used an open-label randomized two-period crossover design in 20 healthy volunteers. Subjects were fasted overnight then randomly assigned (1:1) to dosing sequence AB or BA (A, fasted condition; B, fed condition). Dosing periods were separated by 1 week for both studies. Serial plasma samples from each period were collected and analyzed by LC-MS/MS. PK parameters were calculated using Phoenix WinNonlin® software.ResultsFor the BE study, geometric mean ulotaront Cmax values were 93.28 and 86.98 ng/mL for tablet and capsule, respectively. Cmax ratio was 107.25% (90% CI 101.84-112.94%). Geometric mean ulotaront area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) values were 868.8 and 829.3 ng·h/mL for tablet and capsule, respectively. AUC0-∞ ratio was 104.76% (90% CI 100.68109.01%). For the FE study, geometric mean ulotaront Cmax was 157.89 and 157.95 ng/mL under fed and fasted conditions, respectively. Geometric mean ratio of Cmax was 99.96% (90% CI 94.48-105.77%). Geometric mean ulotaront AUC0-∞ was 1584.2 ng·h/mL fed and 1589.2 ng·h/mL fasted. Geometric mean ratio for AUC0-∞ was 99.69% (90% CI 95.02-104.58%). There was a delay in tmax (median difference 1.47 h) in the fed condition.ConclusionsThe results showed geometric mean ratios and 90% CIs for both Cmax and AUC0-∞ for ulotaront were well within typical bioequivalence criteria of 80-125% for both the BE and FE studies, thereby confirming the bioequivalence of the two dosage forms and no significant food effect.

Dataset Information

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

Publications

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

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