Clinical trial NCT03337308: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipidemias
Keywords: hyperlipidemia
heterozygous familial hypercholesterolemia
atherosclerotic cardiovascular disease
high cholesterol
ASCVD
HeFH
LDL
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-08
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline; Week 12
Secondary outcomes:
measure: Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in Triglycerides (TGs)
timeFrame: Baseline; Week 12
Other outcomes:
Locations:
city: Ames
country: United States
facility: PMG Research of McFarland
state: Iowa
city: Nashua
country: United States
facility: Foundation Cardiology
state: New Hampshire
city: Statesville
country: United States
facility: PMG Research of Piedmont Healthcare
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Knoxville
country: United States
facility: PMG Research of Knoxville
state: Tennessee
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Ron Haberman, MD
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.
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.
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. No abstract available.
citation: 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.