Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized double-blind (ORD) study

Abstract

Background: Hypertriglyceridemia is a risk factor for cardiovascular disease, and clinical practice guidelines advocate treatment to reduce triglyceride (TG) levels. In Japan, an EPA-E (eicosapentaenoic acid-ethyl ester) product has been used clinically for treating dyslipidemia.

Objective: We investigated the TG-lowering effects of TAK-085 (EPA-E + docosahexaenoic acid-ethyl ester) in comparison with EPA-E in Japanese patients with hypertriglyceridemia (TG ≥150 mg/dL and <750 mg/dL).

Methods: In this multicenter, 12-week, double-blind study, subjects were stratified for coadministration of a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor then randomized to TAK-085 2 g once daily (n = 205), TAK-085 2 g twice daily (n = 210), or EPA-E 0.6 g three times daily (n = 195). Each one gram of fatty acid in TAK-085 contains approximately 465 mg of EPA plus 375 mg of docosahexaenoic acid-ethyl as ethyl esters. Guidance on lifestyle modifications was provided throughout.

Results: The primary end point was the percent change in TG levels (baseline from end of treatment), which was -10.8 ± 22.6, -22.9 ± 23.1, and -11.2 ± 25.7 in the TAK-085 2 g/day, TAK-085 4 g/day, and EPA-E 1.8 g/day groups, respectively. TAK-085 4 g/day produced a significantly greater reduction in TG than EPA-E 1.8 g/day (P < .0001), whereas TAK-085 2 g/day was not inferior to EPA-E 1.8 g/day. Changes in other lipid parameters were relatively modest. There were no notable safety or tolerability differences between the groups.

Conclusions: In Japanese patients with modest hypertriglyceridemia who also underwent lifestyle intervention, TAK-085 4 g/day reduced TG more than EPA-E 1.8 g/day. TAK-085 2 g/day had similar effects on TG as EPA-E 1.8 g/day. TAK-085 was well-tolerated.