Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial

Abstract

Aims: Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA.

Methods: In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4×1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA.

Results: A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration-time curve from 0 to 72 h for EPA, DHA, and EPA +DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA+DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively.

Conclusions: The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects.

Trial registration: NCT02372344.

Keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Japan; Omega-3 fatty acids; Pharmacokinetics.

Fig. 1.

Trial design. A: Administration in fasting condition; B: Administration before meal; C: Administration after meal. Each 1-g capsule of OM3-CA contains at least 850 mg of polyunsaturated fatty acids (PUFAs) of which EPA and DHA are the most abundant.

Fig. 2.

Baseline-adjusted plasma concentration–time profiles of (A) total EPA, (B) total DHA, and (C) total EPA + total DHA. Results are presented as the mean ± standard deviation. DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid. Each 1-g capsule of OM3-CA contains at least 850 mg of polyunsaturated fatty acids (PUFAs) of which EPA and DHA are the most abundant.