title: 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.
authors.affiliation: Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Chiba 285-8741, Japan. ichiro.tatsuno@med.toho-u.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Kentarou
authors.initials: K
authors.lastname: Kudou
authors.forename: Jun
authors.initials: J
authors.lastname: Ootake
mesh_terms: D044466:Asian People; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D008019:Life Style; D008297:Male; D014280:Triglycerides / Q000097:blood
chemical_list: D015525:Fatty Acids, Omega-3; D014280:Triglycerides; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid