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

Hyperlipidemias Clinical Trial

Official title:

A Randomized, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of Bempedoic Acid 180 Mg + Ezetimibe 10 Mg Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo Alone in Patients Treated With Maximally Tolerated Statin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03337308
• Other study ID #: 1002FDC-053
• Status: Completed
• Phase: Phase 3
• Start date: October 23, 2017
• Est. completion date: July 18, 2018

Study information

• Verified date: March 2020
• Source: Esperion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 382
• Est. completion date: July 18, 2018
• Est. primary completion date: June 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hyperlipidemias
• Hyperlipoproteinemias

Intervention

Combination Product:
• Bempedoic Acid + Ezetimibe Fixed-Dose Combination
bempedoic acid + ezetimibe FDC 180 mg/10 mg tablet

Drug:
• Bempedoic Acid
bempedoic acid 180 mg tablet
• Ezetimibe
ezetimibe 10 mg overencapsulated tablet
• Placebos
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

Locations

Country	Name	City	State
United States	PMG Research of McFarland	Ames	Iowa
United States	PMG Research of Knoxville	Knoxville	Tennessee
United States	Foundation Cardiology	Nashua	New Hampshire
United States	PMG Research of Piedmont Healthcare	Statesville	North Carolina
United States	PMG Research of Wilmington	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Esperion Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 Ž, 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)	Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the predose Day 1/Week 0 value. Percent change from baseline in hsCRP was analyzed using a non-parametric analysis. Percent change from baseline was calculated as: ([hsCRP value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.	Baseline; Week 12
Secondary	Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the non-HDL-C values from Week -2 and predose Day 1/Week 0. Percent change from baseline in non-HDL-C was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline non-HDL-C as a covariate. Percent change from baseline was calculated as: ([non-HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.	Baseline; Week 12
Secondary	Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the TC values from Week -2 and predose Day 1/Week 0. Percent change from baseline in TC was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline TC as a covariate. Percent change from baseline was calculated as: ([TC value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.	Baseline; Week 12
Secondary	Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)	Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apo B. Baseline was defined as the predose Day 1/Week 0 value. Percent change from baseline in apo B was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline apo B as a covariate. Percent change from baseline was calculated as: ([apo B value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.	Baseline; Week 12
Secondary	Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)	Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was defined as the mean of the HDL-C values from Week -2 and predose Day 1/Week 0. Percent change from baseline was calculated as: ([HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.	Baseline; Week 12
Secondary	Percent Change From Baseline to Week 12 in Triglycerides (TGs)	Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the mean of the TGs values from Week -2 and predose Day 1/Week 0. Percent change from baseline was calculated as: ([TGs value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.	Baseline; Week 12