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Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of an Omega‐3‐Carboxylic Acid Formulation in Healthy Male Japanese Subjects: A Phase 1 Single‐Blind, Randomized, Placebo‐Controlled Trial
Author(s) -
Noda Yoshinori,
Nilsson Catarina,
Shimada Hitoshi,
Kim Hyosung,
Lundström Torbjörn,
Yajima Toshitaka
Publication year - 2018
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.360
Subject(s) - tolerability , medicine , pharmacokinetics , placebo , docosahexaenoic acid , eicosapentaenoic acid , adverse effect , pharmacology , gastroenterology , fatty acid , biochemistry , chemistry , polyunsaturated fatty acid , pathology , alternative medicine
OM3‐CA (omega‐3‐carboxylic acids) is a complex mixture of omega‐3 carboxylic acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is approved in the United States for the treatment of hypertriglyceridemia. As part of its clinical development in Japan, we performed a phase 1 study to investigate the safety, tolerability, and pharmacokinetics after single and multiple doses of OM3‐CA in healthy male Japanese subjects. Eighteen Japanese subjects were allocated to receive 2 or 4 g/day OM3‐CA, or placebo (n = 6 per group). In addition, 6 white subjects received 4 g/day OM3‐CA. The primary objective was to determine the safety and tolerability of OM3‐CA. Plasma concentrations of EPA and DHA were adjusted for baseline values for pharmacokinetic analysis. Overall, OM3‐CA was well tolerated in healthy Japanese subjects. Two Japanese subjects in each group and 5 white subjects experienced adverse events (AEs). Alanine aminotransferase increase was the most common AE in Japanese subjects, also seen with placebo, and diarrhea was the most common AE in white subjects. The maximum plasma concentrations of EPA and DHA were observed 5–6 hours postdose. The pharmacokinetic profiles of EPA and DHA after administration of OM3‐CA were comparable between Japanese and white subjects.