title: Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus.
abstract: OBJECTIVE
  8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (ETC-1002) is a small molecule with a unique mechanism of action shown in nonclinical studies to modulate pathways of cholesterol, fatty acid, and carbohydrate metabolism. In previous phase 2 clinical trials, once daily oral treatment with ETC-1002 significantly reduced low-density lipoprotein-cholesterol in patients with hypercholesterolemia. In this trial, the lipid-lowering efficacy of ETC-1002 was evaluated in patients with type 2 diabetes mellitus and hypercholesterolemia. Additional cardiometabolic biomarkers, including glycemic measures, were also assessed.
  
  
  RESULTS
  A single-center, double-blind, placebo-controlled trial evaluated 60 patients with type 2 diabetes mellitus and elevated low-density lipoprotein-cholesterol. Patients discontinued all diabetes mellitus and lipid-regulating drugs and were randomized to receive ETC-1002 80 mg QD for 2 weeks followed by 120 mg QD for 2 weeks or placebo for 4 weeks. ETC-1002 lowered low-density lipoprotein-cholesterol levels by 43±2.6% (least squares mean±SE), compared with a reduction of 4±2.5% by placebo at day 29 (P<0.0001; primary end point). Non-high-density lipoprotein-cholesterol and total cholesterol were also significantly lowered by ETC-1002 compared with placebo (P<0.0001). High-sensitivity C-reactive protein was reduced by 41% (median) compared with a placebo reduction of 11% (P=0.0011). No clinically meaningful safety findings were observed.
  
  
  CONCLUSIONS
  ETC-1002 lowered low-density lipoprotein-cholesterol and other lipids and demonstrated improvement in high-sensitivity C-reactive protein in patients with type 2 diabetes mellitus and hypercholesterolemia without worsening glycemic control. ETC-1002 was well tolerated in this population.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT# 01607294.
authors.affiliation: From Comprehensive Clinical Development, Miramar, FL (M.J.G.); Esperion Therapeutics Inc, Plymouth, MI (N.L.R., D.E.M., J.C.H., J.R.M., R.S.N.); Integrated Medical Development LLC, Princeton Junction, NJ (P.S.); Milad Consulting, Plymouth, MI (M.A.M.); and United BioSource Corporation, Ann Arbor, MI (S.J.M.).
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gutierrez
authors.forename: Noah L
authors.initials: NL
authors.lastname: Rosenberg
authors.forename: Diane E
authors.initials: DE
authors.lastname: Macdougall
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Hanselman
authors.forename: Janice R
authors.initials: JR
authors.lastname: Margulies
authors.forename: Poul
authors.initials: P
authors.lastname: Strange
authors.forename: Mark A
authors.initials: MA
authors.lastname: Milad
authors.forename: Scott J
authors.initials: SJ
authors.lastname: McBride
authors.forename: Roger S
authors.initials: RS
authors.lastname: Newton
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D003998:Dicarboxylic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D014280:Triglycerides; C581236:8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; D002097:C-Reactive Protein
keywords: cardiovascular diseases; lipid and lipoprotein metabolism; low-density lipoprotein-cholesterol; risk factors; type 2 diabetes mellitus