Evaluation of Major Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (ETC-1002) or Placebo

Cardiovascular Diseases Clinical Trial

— CLEAR Outcomes  

Official title:

A Randomized, Double-blind, Placebo-controlled Study to Assess the Effects of Bempedoic Acid (ETC-1002) on the Occurrence of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02993406
• Other study ID #: 1002-043
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2016
• Est. completion date: November 7, 2022

Study information

• Verified date: December 2023
• Source: Esperion Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if treatment with bempedoic acid (ETC-1002) versus placebo decreases the risk of cardiovascular events in participants who have or are at high risk for cardiovascular disease and are statin intolerant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13970
• Est. completion date: November 7, 2022
• Est. primary completion date: November 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 85 years
• History of, or at high risk for, cardiovascular disease (CVD) including coronary artery disease, symptomatic peripheral arterial disease, cerebrovascular atherosclerotic disease, or at high risk for a cardiovascular event
• Participant-reported SI due to an adverse safety effect that started or increased during statin therapy and resolved or improved when statin therapy was discontinued

resulting in an inability to tolerate:

• 2 or more statins at any dose, or
• 1 statin at any dose and unwilling to attempt a second statin or advised by a physician to not attempt a second statin. Please note that participants currently tolerating very low dose statin therapy (an average daily dose of rosuvastatin <5 mg, atorvastatin <10 mg, simvastatin <10 mg, lovastatin <20 mg, pravastatin <40 mg, fluvastatin <40 mg, or pitavastatin <2 mg) are considered to be intolerant to that low dose statin. Patients may continue taking very low dose statin therapy throughout the study provided that it is stable (used for at least 4 weeks prior to screening) and well tolerated.
• Written confirmation by both participant and investigator that the participant is statin intolerant as defined above, aware of the benefit of statin use to reduce the risk of MACE including death, and also aware that many other participants who are unable to tolerate a statin are able to tolerate a different statin or dose.
• Men and nonpregnant, nonlactating women
• Fasting blood LDL-cholesterol = 100 (2.6 mmol/L) at screening

Exclusion Criteria:

• Fasting blood triglycerides greater than 500 mg/dL (5.6 mmol/L) at screening
• Recent (within 90 days of screening) history of major cardiovascular events, transient ischemic attack (TIA), or unstable or symptomatic cardiac arrhythmia
• History of severe heart failure
• Uncontrolled hypertension or uncontrolled diabetes

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Statin Adverse Reaction

Intervention

Drug:
• Bempedoic acid 180 mg tablet
Patients take bempedoic acid 180 mg tablet orally once daily
• Matching placebo tablet
Patients take matching placebo tablet orally once daily

Locations

Country	Name	City	State
United States	Seton Heart Institute	Austin	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Esperion Therapeutics, Inc.	The Cleveland Clinic

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Croatia,  Czechia,  Denmark,  Estonia,  Germany,  Hungary,  India,  Latvia,  Lithuania,  Mexico,  Netherlands,  New Zealand,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (7)

Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4. — View Citation

Nicholls S, Lincoff AM, Bays HE, Cho L, Grobbee DE, Kastelein JJ, Libby P, Moriarty PM, Plutzky J, Ray KK, Thompson PD, Sasiela W, Mason D, McCluskey J, Davey D, Wolski K, Nissen SE. Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. Am Heart J. 2021 May;235:104-112. doi: 10.1016/j.ahj.2020.10.060. Epub 2020 Oct 24. — View Citation

Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen CF, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y, Nicholls SJ; CLEAR Outcomes Investigators. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056/NEJMoa2215024. Epub 2023 Mar 4. — View Citation

Nissen SE, Menon V, Nicholls SJ, Brennan D, Laffin L, Ridker P, Ray KK, Mason D, Kastelein JJP, Cho L, Libby P, Li N, Foody J, Louie MJ, Lincoff AM. Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients. JAMA. 2023 Jul 11;330(2):131-140. doi: 10.1001/jama.2023.9696. — 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

Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6. — View Citation

Thompson PD, Rubino J, Janik MJ, MacDougall DE, McBride SJ, Margulies JR, Newton RS. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance. J Clin Lipidol. 2015 May-Jun;9(3):295-304. doi: 10.1016/j.jacl.2015.03.003. Epub 2015 Mar 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With First Occurrence of Four Component Major Adverse Cardiovascular Events (MACE)	The primary efficacy end point was a four-component composite of adjudicated MACE, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, as assessed in a time-to first-event analysis.	Up to 68 months
Secondary	Number of Participants With First Occurrence of Three Component MACE	The first key secondary end point was a three-component MACE, defined as death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.	Up to 68 months
Secondary	Number of Participants With First Occurrence of Myocardial Infarction	Number of participants with time to first occurrence of fatal and non-fatal myocardial infarction are presented.	Up to 68 months
Secondary	Number of Participants With Time to First Occurrence of Coronary Revascularization	Number of participants with time to first occurrence of coronary revascularization are presented.	Up to 68 months
Secondary	Number of Participants With Time to First Occurrence of Stroke	Number of participants with time to first occurrence of fatal and non-fatal stroke.	Up to 68 months
Secondary	Number of Participants With Time to Cardiovascular Death	Number of participants with time to cardiovascular death are presented.	Up to 68 months
Secondary	Number of Participants With Time to All-cause Mortality	All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.	Up to 68 months