title: Icosabutate, a Structurally Engineered Fatty Acid, Improves the Cardiovascular Risk Profile in Statin-Treated Patients with Residual Hypertriglyceridemia.
abstract: To evaluate the efficacy and safety of icosabutate, an oral, once-daily, first-in-class medication, in reducing non-high-density lipoprotein cholesterol (non-HDL-C) in patients with persistent hypertriglyceridemia despite statin therapy.
  
  
  
  The study was designed to randomly assign 140 patients with fasting triglyceride levels ≥200 but <500 mg/dl on a stable dose of statin therapy to receive either masked icosabutate 600 mg once daily or a control for 12 weeks. The primary end point was a percentage change in non-HDL-C from baseline to 12 weeks.
  
  
  
  With icosabutate, non-HDL-C levels were reduced (-9.2%) when compared with the control (-0.4%) for a between-group difference of -7.4% (p = 0.02). Compared with the control, icosabutate reduced triglycerides (-27.0%, p < 0.001), very- low-density lipoprotein (VLDL) cholesterol (-31.5%, p < 0.001) and apolipoprotein C-III (-22.5%, p < 0.001). LDL-C levels did not change (0.5%, p = 0.87). HDL-C (10.2%, p < 0.001) was increased. After 113 subjects had been randomized, the study was terminated due to a partial clinical hold imposed by US regulators after observing QT prolongation at supratherapeutic doses of icosabutate in a dog study. In this study, adverse events were balanced between treatment arms, and there were no discontinuations due to adverse events.
  
  
  
  Icosabutate was efficacious in lowering non-HDL-C and other biomarkers of cardiovascular risk and was generally well tolerated.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Jonas
authors.initials: J
authors.lastname: Hallén
authors.forename: Runar
authors.initials: R
authors.lastname: Vige
authors.forename: David A
authors.initials: DA
authors.lastname: Fraser
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Svein Olaf
authors.initials: SO
authors.lastname: Hustvedt
authors.forename: David G
authors.initials: DG
authors.lastname: Orloff
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002087:Butyrates / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004285:Dogs; D004359:Drug Therapy, Combination; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D002087:Butyrates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; C000626078:icosabutate