Pharmacokinetics of Icosapent Ethyl: An Open-Label, Multiple Oral Dose, Parallel Design Study in Healthy Chinese Subjects.

Abstract

Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester that has been approved to lower triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. Before this study, there were no pharmacokinetics (PK) or safety data in Chinese patients after receiving IPE. The purpose of this study was to evaluate the PK of EPA in plasma and red blood cells and safety after oral administration of IPE capsules for 28 consecutive days in healthy Chinese subjects. It was a randomized, open-label, parallel-designed multiple-dose, phase I study. Twenty-four subjects were enrolled and randomly assigned to 2 groups, including 6 men and 6 women in each group. Group A received IPE 2.0 g/day (1×1 g twice daily), and group B received IPE 4.0 g/day (2×1 g twice daily) with dosing after standard meals for 28 days. During the treatment period, PK samples were collected from all subjects before the morning dose on days 1, 14, 26, and 28. Following completion of the last study drug administration in the morning on day 28, an 18-day posttreatment PK sample collection period was followed. Twenty-four eligible subjects were enrolled in this study, and 1 subject withdrew from the study. The main PK parameters (baseline-corrected maximum observed plasma concentration and area under the plasma concentration-time curve during a dosing interval) of plasma total EPA, RBC EPA, and plasma unesterified EPA increased with dose. Chinese healthy subjects who took IPE capsules orally in the dose range of 2.0 to 4.0 g/day for 28 consecutive days were safe and tolerable.