Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant

NCT02988115 | Completed Phase 3 Results DMC

• 1 other identifier: 1002-046
• Study Type: interventional
• Target: 345
• Locations: 2 countries
• Sites: 67

Brief Summary

The purpose of this study is to determine if bempedoic acid (ETC-1002) is effective and safe versus placebo in patients with elevated LDL cholesterol and who are statin-intolerant.

Conditions

Hypercholesterolemia; Atherosclerotic Cardiovascular Disease; Statin Adverse Reaction

Keywords

hyperlipidemia; cholesterol; familial hypercholesterolemia; atherosclerotic cardiovascular disease; ASCVD; HeFH; LDL; statin intolerance

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline (PCFB) in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12

  PCFB was calculated as the (\[post-Baseline (BL) value minus the BL value\] divided by the BL value ) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available, that single value was used as BL. PCFB in LDL-C was analyzed using analysis of covariance (ANCOVA), with treatment group and stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing lipid data at Week 12 who were no longer taking study treatment, missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking study treatment, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.

  Baseline; Week 12

Secondary Outcomes (4)

• Percent Change From Baseline in LDL-C at Week 24

  Baseline; Week 24

• Percent Change From Baseline in the Lipid Profile at Week 12

  Baseline; Week 12

• Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Week 12

  Baseline; Week 12

• Absolute Change From Baseline in LDL-C at Week 12 and Week 24

  Baseline; Week 12; Week 24

Study Arms (2)

bempedoic acid

EXPERIMENTAL

bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing lipid-modifying therapy (not study provided)

Drug: bempedoic acid

placebo

PLACEBO COMPARATOR

Matching placebo tablet taken orally, daily. Patients remain on ongoing lipid-modifying therapy (not study provided)

Other: placebo

Interventions

bempedoic acid DRUG

bempedoic acid 180 mg tablet

Also known as: ETC-1002

bempedoic acid

placebo OTHER

Matching placebo tablet

Also known as: placebo control

placebo

Eligibility Criteria

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

You may qualify if:

• Require lipid-modifying therapy for primary or secondary prevention of cardiovascular disease
• Fasting LDL-C ≥130 mg/dL for primary prevention or LDL-C ≥100 mg/dL for secondary prevention (history of HeFH and/or ASCVD)
• Be statin-intolerant (unable to tolerate 2 or more statins)

You may not qualify if:

• Total fasting triglyceride ≥500 mg/dL
• Renal dysfunction or nephrotic syndrome or history of nephritis
• Body Mass Index (BMI) ≥50 kg/m2
• Significant cardiovascular disease or cardiovascular event in the past 3 months

Sponsors & Collaborators

• Esperion Therapeutics, Inc.: lead

Study Sites (67)

Unknown Facility

Gilbert, Arizona, United States

Location

Unknown Facility

Anaheim, California, United States

Location

Unknown Facility

Long Beach, California, United States

Location

Unknown Facility

Sacramento, California, United States

Location

Unknown Facility

Santa Ana, California, United States

Location

Unknown Facility

Torrance, California, United States

Location

Unknown Facility

Ventura, California, United States

Location

Unknown Facility

Hamden, Connecticut, United States

Location

Unknown Facility

Daytona Beach, Florida, United States

Location

Unknown Facility

Fort Lauderdale, Florida, United States

Location

Site 1

Miami, Florida, United States

Location

Site 2

Miami, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

West Palm Beach, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Savannah, Georgia, United States

Location

Unknown Facility

Meridian, Idaho, United States

Location

Unknown Facility

Evanston, Illinois, United States

Location

Unknown Facility

Evansville, Indiana, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

Waterloo, Iowa, United States

Location

Unknown Facility

Monroe, Louisiana, United States

Location

Unknown Facility

Slidell, Louisiana, United States

Location

Unknown Facility

Tupelo, Mississippi, United States

Location

Unknown Facility

Lincoln, Nebraska, United States

Location

Unknown Facility

Somerset, New Jersey, United States

Location

Unknown Facility

Binghamton, New York, United States

Location

Unknown Facility

Endwell, New York, United States

Location

Unknown Facility

New Windsor, New York, United States

Location

Unknown Facility

Greensboro, North Carolina, United States

Location

Unknown Facility

Morganton, North Carolina, United States

Location

Unknown Facility

Mount Airy, North Carolina, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Marion, Ohio, United States

Location

Unknown Facility

Maumee, Ohio, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, United States

Location

Unknown Facility

Beaver, Pennsylvania, United States

Location

Unknown Facility

Langhorne, Pennsylvania, United States

Location

Unknown Facility

Cumberland, Rhode Island, United States

Location

Unknown Facility

Anderson, South Carolina, United States

Location

Unknown Facility

Summerville, South Carolina, United States

Location

Unknown Facility

Jackson, Tennessee, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

Memphis, Tennessee, United States

Location

Unknown Facility

Amarillo, Texas, United States

Location

Site 1

Dallas, Texas, United States

Location

Site 2

Dallas, Texas, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Clinton, Utah, United States

Location

Unknown Facility

Hampton, Virginia, United States

Location

Unknown Facility

Kenosha, Wisconsin, United States

Location

Unknown Facility

Brossard, Canada

Location

Unknown Facility

Chicoutimi, Canada

Location

Unknown Facility

Gatineau, Canada

Location

Unknown Facility

London, Canada

Location

Unknown Facility

Longueuil, Canada

Location

Unknown Facility

Mirabel, Canada

Location

Unknown Facility

Montreal, Canada

Location

Unknown Facility

Newmarket, Canada

Location

Unknown Facility

Oakville, Canada

Location

Unknown Facility

Peterborough, Canada

Location

Unknown Facility

Pointe-Claire, Canada

Location

Unknown Facility

Saint-Jérôme, Canada

Location

Unknown Facility

Sarnia, Canada

Location

Unknown Facility

Toronto, Canada

Location

Unknown Facility

Victoriaville, Canada

Location

Related Publications (8)

• Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.

  PMID: 27892461 BACKGROUND

• Cholesterol Treatment Trialists' (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.

  PMID: 21067804 BACKGROUND

• Eckel RH. Approach to the patient who is intolerant of statin therapy. J Clin Endocrinol Metab. 2010 May;95(5):2015-22. doi: 10.1210/jc.2009-2689.

  PMID: 20444930 BACKGROUND

• Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6;352(1):20-8. doi: 10.1056/NEJMoa042378.

  PMID: 15635109 BACKGROUND

• Robinson JG, Stone NJ. The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk: a new paradigm supported by more evidence. Eur Heart J. 2015 Aug 14;36(31):2110-2118. doi: 10.1093/eurheartj/ehv182. Epub 2015 May 20.

  PMID: 25994746 BACKGROUND

• Ballantyne CM, Bays HE, Louie MJ, Smart J, Zhang Y, Ray KK. Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid. J Am Heart Assoc. 2022 Aug 2;11(15):e024531. doi: 10.1161/JAHA.121.024531. Epub 2022 Aug 2.

  PMID: 35916348 DERIVED

• Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Flaim J, Ye Z, Catapano AL. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia. JAMA Cardiol. 2020 Oct 1;5(10):1124-1135. doi: 10.1001/jamacardio.2020.2314.

  PMID: 32609313 DERIVED

• Laufs U, Banach M, Mancini GBJ, Gaudet D, Bloedon LT, Sterling LR, Kelly S, Stroes ESG. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc. 2019 Apr 2;8(7):e011662. doi: 10.1161/JAHA.118.011662.

  PMID: 30922146 DERIVED

Related Links

• World Health Organization Fact Sheet No. 317

MeSH Terms

Conditions

Hypercholesterolemia; Atherosclerosis; Hyperlipidemias; Hyperlipoproteinemia Type II

Interventions

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

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Results Point of Contact

• Title: Medical Director
• Organization: Esperion Therapeutics, Inc.

medinfo@esperion.com

1-833-377-7633

Study Officials

• Ron Haberman, MD

  Esperion Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 9, 2016
• Study Start: November 16, 2016
• Primary Completion: March 16, 2018
• Study Completion: March 16, 2018
• Last Updated: April 3, 2020
• Results First Posted: April 3, 2020

Record last verified: 2020-03

Locations

US (52); CA (15)