Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk

NCT02991118 | Completed Phase 3 Results DMC

• 2 other identifiers: 1002-0472016-003486-26
• Study Type: interventional
• Target: 779
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to see if bemedoic acid (ETC-1002) is effective versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol not adequately controlled by their current therapy.

Conditions

Hypercholesterolemia; Atherosclerotic Cardiovascular Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (atherosclerotic cardiovascular diseases \[ASCVD\] and heterozygous familial hypercholesterolemia \[HeFH\]) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 are imputed using multiple imputation method taking into account adherence to treatment.

  Baseline; Week 12

Secondary Outcomes (7)

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

  Baseline; Week 24

• Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

  Baseline; Week 12

• Percent Change From Baseline to Week 12 in Total Cholesterol (TC)

  Baseline; Week 12

• Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B)

  Baseline; Week 12

• Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)

  Baseline; Week 12

Other Outcomes (12)

• Percent Change From Baseline to Week 12 in Triglycerides (TGs)

  Baseline; Week 12

• Percent Change From Baseline to Week 12 in HDL-C

  Baseline; Week 12

• Percent Change From Baseline to Week 52 in LDL-C

  Baseline; Week 52

Study Arms (2)

bempedoic acid

EXPERIMENTAL

bempedoic acid 180 mg/day

Drug: bempedoic acid

Placebo

PLACEBO COMPARATOR

Placebo control

Drug: placebo

Interventions

bempedoic acid DRUG

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

Also known as: ETC-1002

bempedoic acid

placebo DRUG

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

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:

• Fasting LDL-C ≥100 mg/dL
• High cardiovascular risk (diagnosis of HeFH and/or ASCVD)
• Be on maximally tolerated lipid-modifying therapy (LMT), including maximally tolerated statin either alone or in combination with other LMTs

You may not qualify if:

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

Sponsors & Collaborators

• Esperion Therapeutics, Inc.: lead

Study Sites (2)

Unknown Facility

Clearwater, Florida, United States

Location

Unknown Facility

Georgetown, Texas, United States

Location

Related Publications (8)

• Goldberg AC, Leiter LA, Stroes ESG, Baum SJ, Hanselman JC, Bloedon LT, Lalwani ND, Patel PM, Zhao X, Duell PB. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019 Nov 12;322(18):1780-1788. doi: 10.1001/jama.2019.16585.

  PMID: 31714986 BACKGROUND

• 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

• Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3.

  PMID: 26039521 BACKGROUND

• Robinson JG. Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm. 2013 Mar;19(2):139-49. doi: 10.18553/jmcp.2013.19.2.139.

  PMID: 23461430 BACKGROUND

• Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 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. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. No abstract available.

  PMID: 24222016 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

Related Links

• World Health Organization Fact Sheet No. 317
• What Is Familial Hypercholesterolemia

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 9, 2016
• First Posted: December 13, 2016
• Study Start: November 18, 2016
• Primary Completion: August 22, 2018
• Study Completion: August 22, 2018
• Last Updated: April 27, 2020
• Results First Posted: April 27, 2020

Record last verified: 2020-04

Locations

US (2)