title: Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance.
abstract: ETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia.
  
  
  
  To compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C).
  
  
  
  This phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE.
  
  
  
  EZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups.
  
  
  
  In patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836).
authors.affiliation: Department of Cardiology, Hartford Hospital, Hartford, CT, USA. Electronic address: paul.thompson@hhchealth.org.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.affiliation: Esperion Therapeutics Inc., Ann Arbor, MI, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: MacDougall
authors.affiliation: Esperion Therapeutics Inc., Ann Arbor, MI, USA.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Newton
authors.affiliation: Esperion Therapeutics Inc., Ann Arbor, MI, USA.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Margulies
authors.affiliation: Esperion Therapeutics Inc., Ann Arbor, MI, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Hanselman
authors.affiliation: Medpace Inc., Cincinnati, OH, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Orloff
authors.affiliation: School of Pharmacy, Virginia Commonwealth University and National Clinical Research Inc., Richmond, VA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: McKenney
authors.affiliation: Baylor College of Medicine and Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008078:Cholesterol, LDL / Q000097:blood*; D000069438:Ezetimibe / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects; D012449:Safety; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe
keywords: ETC-1002; Ezetimibe; Hypercholesterolemia; Myalgia; Statin intolerance; Statin-associated muscle symptoms