Safety and Pharmacokinetics of DS-8500a, a Novel GPR119 Agonist, After Multiple Oral Doses in Healthy Japanese Males
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.
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.
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.
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).
The authors would like to thank Rita Moreira da Silva, Helen Roberton, Emma Donadieu, and Mary Richardson of Edanz Medical Writing for providing medical writing services.
Compliance with Ethical Standards
This study was funded by Daiichi Sankyo Co., Ltd.
Conflicts of interest
MK, EK, KS, KY, and TT are employees of Daiichi Sankyo Co., Ltd. HF received research funding for this study from Daiichi Sankyo Co., Ltd.
All procedures performed in this study were in accordance with the institutional and national ethical standards and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
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