TITLE:
Safety, Tolerability, and Pharmacokinetics of E3030, a Novel Peroxisome Proliferator-Activated Receptor α/γ Dual Agonist, in Healthy Japanese Male Subjects
AUTHORS:
Yutaka Takeuchi, Yuki Nishioka, Yasumi Kitahara, Setsuo Hasegawa, Akihiro Ohnishi
KEYWORDS:
PPAR Agonist; Phase 1; Pharmacokinetics; Healthy Subjects
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.2,
February
10,
2014
ABSTRACT: Objective: The objectives of the present study were to evaluate the
safety of single oral dose E3030 in healthy Japanese male subjects, and to
evaluate pharmacokinetics after single oral dose E3030 and food effect on pharmacokinetic
profiles. Methods: This study was conducted in a randomized, double-blind,
placebo-controlled, ascending single-dose study in 56 healthy Japanese male
subjects. Subjects were orally administered E3030 (0.5-40 mg) or placebo. Results: Six of 42
(14%) subjects’ administered E3030 experienced
adverse events; however, all adverse events were mild and transient, and there
was no dose-dependent increase in any adverse event. Plasma samples were
collected over 96 hours after dosing. After administration in the fasted state,
Cmax of E3030 was achieved between 1.00 and 1.75 hours, indicating
rapid absorption. Both Cmax and AUC were dose-proportional in the range of 0.5 to 40 mg. The average range of elimination
half-life was 18.4-23.8 hr. CL/F and Vz/F also
remained nearly constant regardless of dose levels. In addition, food effect
was exploratorily evaluated in five subjects of administered
E3030 (10 mg) in both fasted and fed states. The fed/fasted ratios for the
geometric mean of the Cmax and AUC were 0.803 and 0.913,
respectively. Conclusion: E3030 was safe and well tolerated at single doses up
to 40 mg. The pharmacokinetic profile showed good linearity, and food effect on
pharmacokinetics of E3030 was
not significant.