title: Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy.
abstract: ETC-1002 is an oral, once-daily medication that inhibits adenosine triphosphate citrate lyase, an enzyme upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, to reduce cholesterol biosynthesis. ETC-1002 monotherapy has demonstrated significant reduction in low-density lipoprotein cholesterol (LDL-C) compared with placebo in phase 2 studies. The objective of this study was to compare the lipid-lowering efficacy of ETC-1002 versus placebo when added to ongoing statin therapy in patients with hypercholesterolemia. This phase 2b, multicenter, double-blind trial (NCT02072161) randomized 134 hypercholesterolemic patients (LDL-C, 115 to 220 mg/dl) on stable background statin therapy to 12 weeks of add-on treatment with ETC-1002 120 mg, ETC-1002 180 mg, or placebo. The primary efficacy end point was the percent change in calculated LDL-C from baseline to week 12. For LDL-C, the least-squares mean percent change ± standard error from baseline to week 12 was significantly greater with ETC-1002 120 mg (-17 ± 4%, p = 0.0055) and ETC-1002 180 mg (-24 ± 4%, p <0.0001) than placebo (-4 ± 4%). ETC-1002 also dose dependently reduced apolipoprotein B by 15% to 17%, non-high-density lipoprotein cholesterol by 14% to 17%, total cholesterol by 13% to 15%, and LDL particle number by 17% to 21%. All these reductions in ETC-1002-treated cohorts were significantly greater than those with placebo. Rates of adverse events (AEs), muscle-related AEs, and discontinuations for AEs with ETC-1002 were similar to placebo. In conclusion, ETC-1002 120 mg or 180 mg added to stable statin therapy significantly reduced LDL-C compared to placebo and has a similar tolerability profile.
authors.affiliation: Department of Medicine, Baylor College of Medicine and Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. Electronic address: cmb@bcm.edu.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Virginia Commonwealth University and National Clinical Research Inc., Richmond, Virginia.
authors.forename: James M
authors.initials: JM
authors.lastname: McKenney
authors.affiliation: Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
authors.forename: Diane E
authors.initials: DE
authors.lastname: MacDougall
authors.affiliation: Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Margulies
authors.affiliation: Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Robinson
authors.affiliation: Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Hanselman
authors.affiliation: Research and Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
authors.forename: Narendra D
authors.initials: ND
authors.lastname: Lalwani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005227:Fatty Acids / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; C581236:8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; D019821:Simvastatin