A Study Evaluating the Safety and Efficacy of Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo in Patients Treated With Maximally Tolerated Statin Therapy

NCT03337308 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 1002FDC-053
• Study Type: interventional
• Target: 382
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine if Bempedoic Acid (BA) + Ezetimibe (EZE) in a fixed-dose combination (FDC) is effective and safe versus its individual components and placebo in patients with elevated LDL cholesterol treated with maximally tolerated statin therapy.

Conditions

Hyperlipidemias

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the LDL-C values from Week -2 and predose Day 1/Week 0. Percent change from baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group and randomization stratification as a factors and baseline LDL-C as a covariate. Percent change from baseline was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. For LDL-C, if measured LDL-C value was available, measured LDL-C was used.

  Baseline; Week 12

Secondary Outcomes (6)

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

  Baseline; Week 12

• 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-density Lipoprotein Cholesterol (HDL-C)

  Baseline; Week 12

Study Arms (4)

BA 180 mg + EZE 10 mg FDC

EXPERIMENTAL

Bempedoic acid (BA) + ezetimibe (EZE) fixed-dose combination (FDC) 180 mg/10 mg tablets taken orally once daily for 12 weeks

Combination Product: Bempedoic Acid + Ezetimibe Fixed-Dose Combination; Drug: Placebos

BA 180 mg

EXPERIMENTAL

Bempedoic acid (BA) 180 mg tablets taken orally once daily for 12 weeks

Drug: Bempedoic Acid; Drug: Placebos

EZE 10 mg

ACTIVE COMPARATOR

Ezetimibe (EZE) 10 mg overencapsulated tablets taken orally once daily for 12 weeks

Drug: Ezetimibe; Drug: Placebos

Placebos

PLACEBO COMPARATOR

Placebos to match identical bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or identical bempedoic acid 180 mg tablet, or identical ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks

Drug: Placebos

Interventions

Bempedoic Acid + Ezetimibe Fixed-Dose Combination COMBINATION_PRODUCT

bempedoic acid + ezetimibe FDC 180 mg/10 mg tablet

Also known as: Bempedoic Acid + Zetia FDC, ETC-1002 + Zetia

BA 180 mg + EZE 10 mg FDC

Bempedoic Acid DRUG

bempedoic acid 180 mg tablet

Also known as: ETC-1002

BA 180 mg

Ezetimibe DRUG

ezetimibe 10 mg overencapsulated tablet

Also known as: Zetia

EZE 10 mg

Placebos DRUG

placebo tablet or capsule to match bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or bempedoic acid 180 mg tablet, or ezetimibe 10 mg capsule

Also known as: Placebo

BA 180 mg; BA 180 mg + EZE 10 mg FDC; EZE 10 mg; Placebos

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)
• Treated with maximally tolerated statin therapy at stable dose for at least 4 weeks prior to screening

You may not qualify if:

• Total Fasting Triglyceride ≥ 400 mg/dL
• Renal Dysfunction or nephrotic syndrome or history of nephritis
• Significant cardiovascular disease or cardiovascular event within the past 3 months

Sponsors & Collaborators

• Esperion Therapeutics, Inc.: lead

Study Sites (5)

PMG Research of McFarland

Ames, Iowa, 50010, United States

Location

Foundation Cardiology

Nashua, New Hampshire, 03060, United States

Location

PMG Research of Piedmont Healthcare

Statesville, North Carolina, 28625, United States

Location

PMG Research of Wilmington

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Knoxville

Knoxville, Tennessee, 37912, United States

Location

Related Publications (6)

• 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

• Authors/Task Force Members:; Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Z, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016 Oct;253:281-344. doi: 10.1016/j.atherosclerosis.2016.08.018. Epub 2016 Sep 1. No abstract available.

  PMID: 27594540 BACKGROUND

• Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, Braunwald E, Sabatine MS. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016 Sep 27;316(12):1289-97. doi: 10.1001/jama.2016.13985.

  PMID: 27673306 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, Laufs U, Ray KK, Leiter LA, Bays HE, Goldberg AC, Stroes ES, MacDougall D, Zhao X, Catapano AL. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2020 Apr;27(6):593-603. doi: 10.1177/2047487319864671. Epub 2019 Jul 29.

  PMID: 31357887 DERIVED

MeSH Terms

Conditions

Hyperlipidemias; Atherosclerosis; Hypercholesterolemia

Interventions

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

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

After a Root Cause Analysis, three sites were found not to have followed Good Clinical Practice; therefore, analysis was completed with all data from these sites removed.

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: 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: November 6, 2017
• First Posted: November 8, 2017
• Study Start: October 23, 2017
• Primary Completion: June 18, 2018
• Study Completion: July 18, 2018
• Last Updated: April 8, 2020
• Results First Posted: April 8, 2020

Record last verified: 2020-03

Locations

US (5)