Pharmacokinetics of Single Doses of BI 425809 in Healthy Chinese and Japanese Subjects: A Randomized Study

Abstract

Purpose: This study's primary goal was to evaluate the safety profile, tolerability, pharmacokinetics, and dose proportionality of BI 425809, a potent and selective inhibitor of glycine transporter 1, in healthy Chinese and Japanese subjects.

Methods: This single center, double-blind, single-rising dose study conducted in Korea randomly assigned (3:1) subjects within each ethnic subgroup (Chinese and Japanese) to receive a single dose of BI 425809 (10, 25, or 50 mg) or placebo. The primary end point was number (%) of subjects with drug-related adverse events (AEs). Secondary end points included AUC, C_max, t_max, and t_½ for BI 425809 in plasma. The CL/F and volume of distribution (V_z/F) were also measured.

Findings: Of the 49 subjects enrolled into the study (24 Chinese, 25 Japanese), 36 were randomly assigned to receive BI 425809 (12 per dose group) and 13 to receive placebo. All subjects were analyzed for the primary end point and completed the study. Overall, 4 of 49 subjects (8.2%) reported ≥1 AE (placebo: n = 1, BI 425809: n = 3). One drug-related AE of moderate somnolence was reported by a Japanese subject who received placebo. In both subgroups, slightly lower than dose-proportional increases in exposure (AUC and C_max) were observed with increasing dose. In addition, median t_max was 3.5-4.0 h, with a geometric mean t_½ of 29.0-41.2 h. CL/F was similar between Chinese and Japanese subjects and increased with increasing dose (10-50 mg: 68.1-111 mL/min). V_z/F was 209-315 L and similar between the subgroups.

Implications: BI 425809 was generally well tolerated in healthy Chinese and Japanese subjects with no significant findings for tolerability. No apparent difference in the pharmacokinetic variables of BI 425809 was observed between Chinese and Japanese subjects. The safety profile results and pharmacokinetic exposure levels are consistent with previous trials in Caucasian subjects. ClinicalTrials.gov identifier: NCT02383888.

Keywords: Asian population; BI 425809; ethnicity; pharmacokinetics; safety; tolerability.