Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance

Journal of Clinical Lipidology

Volumn 10, Issue 3, 2016, Pages 556-567

  Thompson, Paul D ^a   MacDougall, Diane E ^b   Newton, Roger S ^b   Margulies, Janice R ^b   Hanselman, Jeffrey C ^b   Orloff, David G ^c   McKenney, James M ^d   Ballantyne, Christie M ^e  

^a HARTFORD HOSPITAL   (United States)

^b Esperion Therapeutics Inc   (United States)

^c Medpace Inc ^*  (United States)

^d VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^e HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

Author keywords

ETC 1002; Ezetimibe; Hypercholesterolemia; Myalgia; Statin intolerance; Statin associated muscle symptoms

Indexed keywords

ALANINE AMINOTRANSFERASE; APOLIPOPROTEIN B; ASPARTATE AMINOTRANSFERASE; ATORVASTATIN; BEMPEDOIC ACID; C REACTIVE PROTEIN; EZETIMIBE; FLUINDOSTATIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; PITAVASTATIN; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR;

ADULT; ARTHRALGIA; ARTICLE; BACKACHE; CHOLESTEROL BLOOD LEVEL; CONSTIPATION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEMALE; HEADACHE; HEMATOTHORAX; HUMAN; HYPERCHOLESTEROLEMIA; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTICENTER STUDY; MUSCLE SPASM; MUSCLE WEAKNESS; MUSCULOSKELETAL CHEST PAIN; MUSCULOSKELETAL STIFFNESS; MYALGIA; PANCREATITIS; PHASE 2 CLINICAL TRIAL; PHYSICAL EXAMINATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE BLIND PROCEDURE; TRANSIENT ISCHEMIC ATTACK; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; WAIST CIRCUMFERENCE; ADOLESCENT; AGED; BLOOD; CLINICAL TRIAL; DRUG EFFECTS; MIDDLE AGED; MUSCLE; SAFETY; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; CHOLESTEROL, LDL; EZETIMIBE; FEMALE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; MALE; MIDDLE AGED; MUSCLES; SAFETY; YOUNG ADULT;

EID: 84959421577     PISSN: 19332874     EISSN: 18764789     Source Type: Journal    
DOI: 10.1016/j.jacl.2015.12.025     Document Type: Article

References (21)

1. J.R. Guyton, H.E. Bays, S.M. Grundy, and T.A. Jacobson An assessment by the Statin Intolerance Panel: 2014 update J Clin Lipidol 8 Suppl 3 2014 S72 S81
2. M.K. Ito, K.C. Maki, E.A. Brinton, and et al. Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study J Clin Lipid 8 2014 69 76
3. B.A. Parker, J.A. Capizzi, A.S. Grimaldi, and et al. Effect of statins on skeletal muscle function Circulation 127 2013 96 103
4. E.S. Stroes, P.D. Thompson, A. Corsini, and et al. European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management Eur Heart J 36 2015 1012 1022
5. W.M. Mampuya, D. Frid, M. Rocco, and et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience Am Heart J 166 2013 597 603
6. N.J. Stone, J. Robinson, A.H. Lichtenstein, and et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 63 25 Pt B 2014 2889 2934
7. S.L. Pinkosky, S. Filippov, R.A. Srivastava, and et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism J Lipid Res 54 2013 134 151
8. S. Filippov, S.L. Pinkosky, and R.S. Newton LDL-cholesterol reduction in patients with hypercholesterolemia by modulation of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase Curr Opin Lipidol 25 2014 309 315
9. T.A. Berkhout, L.M. Havekes, N.J. Pearce, and P.H. Groot The effect of (-)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2 Biochem J 272 1990 181 186
10. C.M. Ballantyne, M.H. Davidson, D.E. MacDougall, and et al. Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial J Am Coll Cardiol 62 2013 1154 1162
11. M.J. Gutierrez, N.L. Rosenberg, D.E. MacDougall, and et al. 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 Arterioscler Thromb Vasc Biol 34 2014 676 683
12. P.D. Thompson, J. Rubino, M.J. Janik, and et al. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance J Clin Lipidol 9 2015 295 304
13. Ezetimibe (Zetia) [package insert] 2013 Merck & Co., Inc. Whitehouse Station, NJ
14. R.S. Rosenson, S.K. Baker, T.A. Jacobson, S.L. Kopecky, and B.A. Parker An assessment by the Statin Muscle Safety Task Force: 2014 update J Clin Lipidol 8 Suppl 3 2014 S58 S71
15. E.A. Stein, C.M. Ballantyne, E. Windler, and et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins Am J Cardiol 101 2008 490 496
16. V.G. Saougos, A.P. Tambaki, M. Kalogirou, and et al. Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2 Arterioscler Thromb Vasc Biol 27 2007 2236 2243
17. M.H. Davidson, M.A. Dillon, B. Gordon, and et al. Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects Arch Intern Med 159 1999 1893 1900
18. R.H. Knopp, W.V. Brown, C.A. Dujovne, and et al. Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia Am J Med 83 1987 50 59
19. E. Stroes, D. Colquhoun, D. Sullivan, et al. GAUSS-2 Investigators Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab J Am Coll Cardiol 63 2014 2541 2548
20. Moriarty PM, Thompson PD, Cannon CP, et al. ODYSSEY ALTERNATIVE: efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody, alirocumab, versus ezetimibe, in patients with statin intolerance as defined by a placebo run-in and statin rechallenge arm. Presented at: American Heart Association 2014 Scientific Sessions; November 17, 2014; Chicago, IL.
21. J.P. Kane New horizons in lipid management J Am Coll Cardiol 62 2013 1163 1164