Clinical trial NCT02991118: Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk
Official title: A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk Not Adequately Controlled by Their Lipid-Modifying Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Atherosclerotic Cardiovascular Disease
Keywords: hyperlipidemia
cholesterol
familial hypercholesterolemia
atherosclerotic cardiovascular disease
ASCVD
HeFH
LDL
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-13
Enrollment: 779
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 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

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 24 in LDL-C
timeFrame: Baseline; Week 24
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-sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline; Week 12
measure: Change From Baseline to Week 12 in LDL-C
timeFrame: Baseline; Week 12
measure: Change From Baseline to Week 24 in LDL-C
timeFrame: Baseline; Week 24
Other outcomes:
measure: Percent Change From Baseline to Week 12 in Triglycerides (TGs)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 12 in HDL-C
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline to Week 52 in LDL-C
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in Non-HDL-C
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in Non-HDL-C
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in TC
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in TC
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in Apo B
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in Apo B
timeFrame: Baseline; Week 52
measure: Percent Change From Baseline to Week 24 in hsCRP
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 52 in hsCRP
timeFrame: Baseline; Week 52
measure: Change From Baseline to Week 52 in LDL-C
timeFrame: Baseline; Week 52
Locations:
city: Clearwater
country: United States
state: Florida
city: Georgetown
country: United States
state: Texas
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Ron Haberman, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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: 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.
citation: 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.
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, 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.
citation: 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.