PMID- 31005336 OWN - NLM STAT- MEDLINE DCOM- 20200407 LR - 20221207 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 41 IP - 5 DP - 2019 May TI - Pharmacokinetics of Single Doses of BI 425809 in Healthy Chinese and Japanese Subjects: A Randomized Study. PG - 961-971 LID - S0149-2918(19)30129-8 [pii] LID - 10.1016/j.clinthera.2019.03.014 [doi] AB - 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((1/2)) 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((1/2)) 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. CI - Copyright (c) 2019. Published by Elsevier Inc. FAU - Tsuda, Yasuhiro AU - Tsuda Y AD - Nippon Boehringer Ingelheim Co Ltd, Kobe, Japan. Electronic address: yasuhiro.tsuda@boehringer-ingelheim.com. FAU - Ugai, Hiroyuki AU - Ugai H AD - Nippon Boehringer Ingelheim Co Ltd, Tokyo, Japan. FAU - Wunderlich, Glen AU - Wunderlich G AD - Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario, Canada. FAU - Shin, Jae-Gook AU - Shin JG AD - Inje University Busan Paik Hospital, Busan, South Korea. LA - eng SI - ClinicalTrials.gov/NCT02383888 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190417 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (BI 425809) RN - 0 (Organic Chemicals) SB - IM MH - Adult MH - Area Under Curve MH - *Asian People MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Humans MH - Japan MH - Male MH - Organic Chemicals/*pharmacokinetics MH - Republic of Korea MH - Young Adult OTO - NOTNLM OT - Asian population OT - BI 425809 OT - ethnicity OT - pharmacokinetics OT - safety OT - tolerability EDAT- 2019/04/22 06:00 MHDA- 2020/04/09 06:00 CRDT- 2019/04/22 06:00 PHST- 2018/11/30 00:00 [received] PHST- 2019/03/04 00:00 [revised] PHST- 2019/03/25 00:00 [accepted] PHST- 2019/04/22 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/04/22 06:00 [entrez] AID - S0149-2918(19)30129-8 [pii] AID - 10.1016/j.clinthera.2019.03.014 [doi] PST - ppublish SO - Clin Ther. 2019 May;41(5):961-971. doi: 10.1016/j.clinthera.2019.03.014. Epub 2019 Apr 17.