BACKGROUND AND OBJECTIVES:G protein-coupled receptor 119 (GPR119) agonists reduce plasma glucose by promoting insulin secretion in a glucose-dependent manner. We evaluated the safety and pharmacokinetics of multiple oral doses of DS-8500a, a GPR119 agonist, under fed conditions in healthy adult Japanese male subjects. METHODS: In this Phase 1, randomized, placebo-controlled, double-blind, multiple oral dose study, participants were aged ≥ 20 and ≤ 45 years with a body mass index ≥ 18.5 and < 25.0 kg/m2. DS-8500a 50 and 100 mg or placebo were administered orally, once daily, 30 min after breakfast for 7 days. The primary endpoints were pharmacokinetics and safety. RESULTS: Twenty-four subjects were included (6, 9, and 9 in the placebo, 50-, and 100-mg groups, respectively). On Day 7, the mean maximum plasma concentration (Cmax) was 812 ng/mL in the 50-mg group and 1310 ng/mL in the 100-mg group. The mean area under the plasma concentration-time curve during dosing interval (AUCtau) was 7910 and 13,200 ng·h/mL in the two treatment groups, respectively. The observed accumulation ratio was 1.25 in the 50-mg group and 1.32 in the 100-mg group. All adverse events were mild and judged unrelated to the study drug. CONCLUSIONS:DS-8500a plasma concentrations reached steady state from Day 3, and Cmax and AUCtau increased in a less than dose-proportional manner. After repeated doses of DS-8500a at 100 mg, the DS-8500a trough concentration was expected to reach a pharmacologically active dose. DS-8500a was well tolerated up to 100 mg after a 7-day administration. STUDY REGISTRY IDENTIFICATION: JAPIC ID: JapicCTI-173550 (registered retrospectively on 30 March 2017).
RCT Entities:
BACKGROUND AND OBJECTIVES:G protein-coupled receptor 119 (GPR119) agonists reduce plasma glucose by promoting insulin secretion in a glucose-dependent manner. We evaluated the safety and pharmacokinetics of multiple oral doses of DS-8500a, a GPR119 agonist, under fed conditions in healthy adult Japanese male subjects. METHODS: In this Phase 1, randomized, placebo-controlled, double-blind, multiple oral dose study, participants were aged ≥ 20 and ≤ 45 years with a body mass index ≥ 18.5 and < 25.0 kg/m2. DS-8500a 50 and 100 mg or placebo were administered orally, once daily, 30 min after breakfast for 7 days. The primary endpoints were pharmacokinetics and safety. RESULTS: Twenty-four subjects were included (6, 9, and 9 in the placebo, 50-, and 100-mg groups, respectively). On Day 7, the mean maximum plasma concentration (Cmax) was 812 ng/mL in the 50-mg group and 1310 ng/mL in the 100-mg group. The mean area under the plasma concentration-time curve during dosing interval (AUCtau) was 7910 and 13,200 ng·h/mL in the two treatment groups, respectively. The observed accumulation ratio was 1.25 in the 50-mg group and 1.32 in the 100-mg group. All adverse events were mild and judged unrelated to the study drug. CONCLUSIONS:DS-8500a plasma concentrations reached steady state from Day 3, and Cmax and AUCtau increased in a less than dose-proportional manner. After repeated doses of DS-8500a at 100 mg, the DS-8500a trough concentration was expected to reach a pharmacologically active dose. DS-8500a was well tolerated up to 100 mg after a 7-day administration. STUDY REGISTRY IDENTIFICATION: JAPIC ID: JapicCTI-173550 (registered retrospectively on 30 March 2017).
Authors: Wendy L Bennett; Nisa M Maruthur; Sonal Singh; Jodi B Segal; Lisa M Wilson; Ranee Chatterjee; Spyridon S Marinopoulos; Milo A Puhan; Padmini Ranasinghe; Lauren Block; Wanda K Nicholson; Susan Hutfless; Eric B Bass; Shari Bolen Journal: Ann Intern Med Date: 2011-03-14 Impact factor: 25.391
Authors: Zhi-Liang Chu; Chris Carroll; Jean Alfonso; Veronica Gutierrez; Hongmei He; Annette Lucman; Melinda Pedraza; Helen Mondala; Hui Gao; Didier Bagnol; Ruoping Chen; Robert M Jones; Dominic P Behan; James Leonard Journal: Endocrinology Date: 2008-01-17 Impact factor: 4.736
Authors: Zhi-Liang Chu; Robert M Jones; Hongmei He; Chris Carroll; Veronica Gutierrez; Annette Lucman; Molly Moloney; Hui Gao; Helen Mondala; Didier Bagnol; David Unett; Yin Liang; Keith Demarest; Graeme Semple; Dominic P Behan; James Leonard Journal: Endocrinology Date: 2007-02-08 Impact factor: 4.736