PMID- 27138185
OWN - NLM
STAT- MEDLINE
DCOM- 20170502
LR  - 20180228
IS  - 1879-1913 (Electronic)
IS  - 0002-9149 (Linking)
VI  - 117
IP  - 12
DP  - 2016 Jun 15
TI  - Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in 
      Hypercholesterolemic Patients Receiving Statin Therapy.
PG  - 1928-33
LID - S0002-9149(16)30430-1 [pii]
LID - 10.1016/j.amjcard.2016.03.043 [doi]
AB  - 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.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Ballantyne, Christie M
AU  - Ballantyne CM
AD  - Department of Medicine, Baylor College of Medicine and Houston Methodist DeBakey 
      Heart and Vascular Center, Houston, Texas. Electronic address: cmb@bcm.edu.
FAU - McKenney, James M
AU  - McKenney JM
AD  - Virginia Commonwealth University and National Clinical Research Inc., Richmond, 
      Virginia.
FAU - MacDougall, Diane E
AU  - MacDougall DE
AD  - Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
FAU - Margulies, Janice R
AU  - Margulies JR
AD  - Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
FAU - Robinson, Paula L
AU  - Robinson PL
AD  - Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
FAU - Hanselman, Jeffrey C
AU  - Hanselman JC
AD  - Clinical Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
FAU - Lalwani, Narendra D
AU  - Lalwani ND
AD  - Research and Development, Esperion Therapeutics, Inc., Ann Arbor, Michigan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160406
PL  - United States
TA  - Am J Cardiol
JT  - The American journal of cardiology
JID - 0207277
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Dicarboxylic Acids)
RN  - 0 (Fatty Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Hypolipidemic Agents)
RN  - 1EJ6Z6Q368 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cholesterol, LDL/*blood/drug effects
MH  - Dicarboxylic Acids/*therapeutic use
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Fatty Acids/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use
MH  - Hypercholesterolemia/blood/*drug therapy
MH  - Hypolipidemic Agents/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Simvastatin/therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2016/05/04 06:00
MHDA- 2017/05/04 06:00
CRDT- 2016/05/04 06:00
PHST- 2015/12/01 00:00 [received]
PHST- 2016/03/18 00:00 [revised]
PHST- 2016/03/18 00:00 [accepted]
PHST- 2016/05/04 06:00 [entrez]
PHST- 2016/05/04 06:00 [pubmed]
PHST- 2017/05/04 06:00 [medline]
AID - S0002-9149(16)30430-1 [pii]
AID - 10.1016/j.amjcard.2016.03.043 [doi]
PST - ppublish
SO  - Am J Cardiol. 2016 Jun 15;117(12):1928-33. doi: 10.1016/j.amjcard.2016.03.043. 
      Epub 2016 Apr 6.