Safety, Tolerability, and Pharmacokinetics of E3030, a Novel Peroxisome Proliferator-Activated Receptor <i>α/γ</i> Dual Agonist, in Healthy Japanese Male Subjects

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, C max of E3030 was achieved between 1.00 and 1.75 hours, indicating rapid absorption. Both C max and AUC were dose-propor tional 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 V z /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 C max 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.