A Phase 1 Randomized, Placebo‐Controlled Study Assessing the Pharmacokinetics, Safety, and Tolerability of Retosiban in Healthy, Nonpregnant Japanese Subjects

Abstract

This study characterized the pharmacokinetics, safety, and tolerability of retosiban in healthy, nonpregnant Japanese women prior to the enrollment of Japanese women in preterm labor in phase 3 trials. This study had 2 cohorts. Cohort 1 was a double-blind, sponsor-open, randomized study in Japanese women. Cohort 2 was an open-label study in white women to compare the pharmacokinetics with those of Japanese women.Retosiban was administered as a 6 mg/h infusion for 24 hours, followed by a 12 mg/h infusion over the next 24 hours; each infusion was preceded by a 6 mg loading dose administered over 5 minutes. Plasma concentrations of retosiban and its major metabolite, GSK2847065, were determined with an informal comparison of pharmacokinetics between Japanese and white women. There was minimal difference in exposure to retosiban or GSK2847065 between Japanese and white women (ratio of 1.03 in retosiban AUC and C max ). The 2 doses of retosiban were well tolerated across both populations, and no ethnic difference was observed in the safety profile. Given the results of this study and the known safety profile and dosing flexibility in the phase 3 trials, ethnic-specific dose adjustment of retosiban is not considered necessary for the Japanese and general Asian population.