Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients

NCT01941836 | Completed Phase 2

• 1 other identifier: 1002-008
• Study Type: interventional
• Target: 349
• Locations: 1 country
• Sites: 68

Brief Summary

The purpose of this research study is to see how ETC-1002 is tolerated in the body, to measure the amount of ETC-1002 in the blood, and to determine how ETC-1002 affects the level of LDL-cholesterol (bad cholesterol) and other markers of health and disease in blood and urine in patients with elevated LDL-cholesterol with or without statin intolerance.

Conditions

Hypercholesterolemia

Keywords

Statin intolerant; Statin tolerant; LDL; Cholesterol

Outcome Measures

Primary Outcomes (1)

• Percent change in calculated low density lipoprotein-cholesterol (LDL-C)

  Baseline and 12 weeks

Secondary Outcomes (6)

• Percent change in other lipid measures non high density lipoprotein cholesterol (nonHDL-C)

  Baseline and 12 weeks

• Safety using adverse event reports; vital signs

  up to 21 weeks including screening

• Percent change in Apolipoprotein B (ApoB)

  Baseline and 12 weeks

• Percent change in high sensitivity C-reactive protein (hsCRP)

  Baseline and 12 weeks

• Safety using adverse event reports; clinical laboratory results

  up to 21 weeks including screening

Other Outcomes (1)

• Pharmacokinetic plasma trough concentrations of ETC-1002 and its metabolite ESP15228

  Week 2, Week 4, Week 8 and Week 12

Study Arms (5)

ETC-1002 120 mg/day

EXPERIMENTAL

Orally, once daily in morning as capsules

Drug: ETC-1002

ETC-1002 180 mg/day

EXPERIMENTAL

Orally, once daily in morning as capsules

Drug: ETC-1002

ezetimibe 10mg/day

ACTIVE COMPARATOR

Orally, once daily in morning as capsules

Drug: Ezetimibe

ETC-1002 120 mg/day + ezetimibe 10mg/day

EXPERIMENTAL

Orally, once daily in morning

Drug: ETC-1002; Drug: Ezetimibe

ETC-1002 180 mg/day + ezetimibe 10mg/day

EXPERIMENTAL

Orally, once daily in morning

Drug: ETC-1002; Drug: Ezetimibe

Interventions

ETC-1002 DRUG

Patients receive ETC-1002

ETC-1002 120 mg/day; ETC-1002 120 mg/day + ezetimibe 10mg/day; ETC-1002 180 mg/day; ETC-1002 180 mg/day + ezetimibe 10mg/day

Ezetimibe DRUG

Patients receive ezetimibe

Also known as: Zetia

ETC-1002 120 mg/day + ezetimibe 10mg/day; ETC-1002 180 mg/day + ezetimibe 10mg/day; ezetimibe 10mg/day

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Statin intolerant and statin tolerant
• Fasting LDL-C between 130 mg/dL and 220 mg/dL
• Fasting triglyceride less than or equal to 400 mg/dL
• Body mass index (BMI) between 18 and 45 kg/m2

You may not qualify if:

• History or current clinically significant cardiovascular disease
• History or current type 1 diabetes or uncontrolled type 2 diabetes
• Use of metformin or thiazolidinediones (TZD) within 3 months of screening
• History of joint symptoms difficult to differentiate from myalgia
• Uncontrolled hypothyroidism
• Liver disease or dysfunction
• Renal dysfunction or nephritic syndrome
• Gastrointestinal (GI) conditions or prior GI procedures
• HIV or AIDS
• History or malignancy
• History or drug or alcohol abuse within last 2 years
• Use of experimental or investigational drugs within 30 days of screening
• Use of ETC-1002 in a previous clinical study

Sponsors & Collaborators

• Esperion Therapeutics, Inc.: lead
• Medpace, Inc.: collaborator

Study Sites (68)

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Birmingham, Alabama, 35209, United States

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Muscle Shoals, Alabama, 35662, United States

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Chandler, Arizona, 85224, United States

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Beverly Hills, California, 90211, United States

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Chino, California, 91710, United States

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Lincoln, California, 95821, United States

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Long Beach, California, 90806, United States

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Los Angeles, California, 90059, United States

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Newport Beach, California, 92663, United States

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Thousand Oaks, California, 91360, United States

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Vista, California, 92083, United States

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Denver, Colorado, 80220, United States

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Hartford, Connecticut, 06102, United States

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Atlantis, Florida, 33462, United States

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Brandon, Florida, 33511, United States

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Hialeah, Florida, 33012, United States

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Jacksonville, Florida, 32223, United States

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Oviedo, Florida, 32765, United States

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Ponte Vedra, Florida, 32081, United States

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Port Orange, Florida, 32127, United States

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St. Petersburg, Florida, 33756, United States

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West Palm Beach, Florida, 33409, United States

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Decatur, Georgia, 30033, United States

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Marietta, Georgia, 30066, United States

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Meridian, Idaho, 83646, United States

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Evansville, Indiana, 47714, United States

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Kansas City, Kansas, 66214, United States

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Auburn, Maine, 04210, United States

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Lincoln, Nebraska, 68510, United States

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Clifton, New Jersey, 07012, United States

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Albuquerque, New Mexico, 87106, United States

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New Windsor, New York, 12553, United States

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Rochester, New York, 14609, United States

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Williamsville, New York, 14221, United States

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Greensboro, North Carolina, 27408, United States

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Raleigh, North Carolina, 27609, United States

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Salisbury, North Carolina, 28144, United States

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Wilmington, North Carolina, 28401, United States

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Beachwood, Ohio, 26900, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45227, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43213, United States

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Franklin, Ohio, 45005, United States

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Lyndhurst, Ohio, 44124, United States

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Marion, Ohio, 43302, United States

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Willoughby Hills, Ohio, 44094, United States

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Oklahoma City, Oklahoma, 73103, United States

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Tulsa, Oklahoma, 74136, United States

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Eugene, Oregon, 97404, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Kingsport, Tennessee, 37660, United States

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Austin, Texas, 78731, United States

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Dallas, Texas, 75216, United States

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Dallas, Texas, 75230, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77072, United States

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Houston, Texas, 77074, United States

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Round Rock, Texas, 78681, United States

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Orem, Utah, 84058, United States

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Salt Lake City, Utah, 84124, United States

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Norfolk, Virginia, 23502, United States

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Richmond, Virginia, 23294, United States

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Olympia, Washington, 98502, United States

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Renton, Washington, 98057, United States

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Seattle, Washington, 98104, United States

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Spokane, Washington, 99204, United States

Location

Related Publications (5)

• Ballantyne CM, Davidson MH, Macdougall DE, Bays HE, Dicarlo LA, Rosenberg NL, Margulies J, Newton RS. 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. 2013 Sep 24;62(13):1154-62. doi: 10.1016/j.jacc.2013.05.050. Epub 2013 Jun 13.

  PMID: 23770179 BACKGROUND

• Filippov S, Pinkosky SL, Lister RJ, Pawloski C, Hanselman JC, Cramer CT, Srivastava RAK, Hurley TR, Bradshaw CD, Spahr MA, Newton RS. ETC-1002 regulates immune response, leukocyte homing, and adipose tissue inflammation via LKB1-dependent activation of macrophage AMPK. J Lipid Res. 2013 Aug;54(8):2095-2108. doi: 10.1194/jlr.M035212. Epub 2013 May 24.

  PMID: 23709692 BACKGROUND

• Pinkosky SL, Filippov S, Srivastava RA, Hanselman JC, Bradshaw CD, Hurley TR, Cramer CT, Spahr MA, Brant AF, Houghton JL, Baker C, Naples M, Adeli K, Newton RS. 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. 2013 Jan;54(1):134-51. doi: 10.1194/jlr.M030528. Epub 2012 Nov 1.

  PMID: 23118444 BACKGROUND

• Gutierrez MJ, Rosenberg NL, Macdougall DE, Hanselman JC, Margulies JR, Strange P, Milad MA, McBride SJ, Newton RS. 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. 2014 Mar;34(3):676-83. doi: 10.1161/ATVBAHA.113.302677. Epub 2014 Jan 2.

  PMID: 24385236 BACKGROUND

• Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6.

  PMID: 27206943 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Diane E MacDougall, MS

  Esperion Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 13, 2013
• Study Start: September 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: March 29, 2019

Record last verified: 2019-03

Locations

US (68)