title: Icosabutate for the treatment of very high triglycerides: A placebo-controlled, randomized, double-blind, 12-week clinical trial.
abstract: BACKGROUND
  Icosabutate is a structurally enhanced omega-3 fatty acid molecule developed with the aim of achieving improved triglyceride (TG)-lowering efficacy, increased potency, and preserved safety compared with conventional prescription omega-3 fatty acid.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of icosabutate 600 mg once daily in patients with very high TGs.
  
  
  METHODS
  After a 6-8 week run-in period, men and women with TG levels ≥ 500 mg/dL and ≤ 1500 mg/dL were randomized to double-blind treatment with placebo or icosabutate 600 mg for 12 weeks. The primary end point was % change from baseline in TGs at 12 weeks.
  
  
  RESULTS
  A total of 87 subjects were randomized. At baseline, median TG (interquartile range) levels were 611 (543-878) and 688 (596-892) mg/dL, and the median change after 12 weeks of treatment was -51% and -17%, respectively, for a placebo-corrected change of -33% (P < .001). Adjusted for placebo, icosabutate significantly reduced very low-density lipoprotein cholesterol (-36%, P < .001), remnant lipoprotein cholesterol (-34%, P < .001), apolipoprotein (Apo) C-III (-35%, P < .001), trended toward reduced non-high-density lipoprotein cholesterol (-7%, P = .064); significantly increased high-density lipoprotein cholesterol (18%, P < .001) and low-density lipoprotein cholesterol (28%, P < .001), with a trend of an increased lipoprotein (a; 10%, P = .054). No changes were observed in total cholesterol, apolipoprotein B, or apolipoprotein A1. Fasting plasma glucose was unchanged, whereas fasting plasma insulin was reduced (P = .001) with icosabutate. Icosabutate was generally well tolerated.
  
  
  CONCLUSIONS
  Treatment with icosabutate once daily significantly reduced TG, very low-density lipoprotein cholesterol, and Apo C-III levels in patients with very high TG levels. This trial was registered at www.clinicaltrials.gov as NCT01893515.
authors.affiliation: L-MARC Research Center, Louisville, KY, USA.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.affiliation: Pronova BioPharma, Lysaker, Norway.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hallén
authors.affiliation: Pronova BioPharma, Lysaker, Norway.
authors.forename: Runar
authors.initials: R
authors.lastname: Vige
authors.affiliation: Pronova BioPharma, Lysaker, Norway.
authors.forename: David
authors.initials: D
authors.lastname: Fraser
authors.affiliation: Medpace, Inc, Cincinatti, OH, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Pronova BioPharma, Lysaker, Norway.
authors.forename: Svein Olaf
authors.initials: SO
authors.lastname: Hustvedt
authors.affiliation: Medpace, Inc, Cincinatti, OH, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Orloff
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: j.j.kastelein@amc.uva.nl.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D015525:Fatty Acids, Omega-3; D000960:Hypolipidemic Agents; D010919:Placebos; D014280:Triglycerides
keywords: Apolipoprotein C-III; Hypertriglyceridemia; Icosabutate; Remnants; Triglycerides