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

Phase 3

Completed

Conditions: Cardiovascular Diseases
Statin Adverse Reaction

Interventions: Drug: Bempedoic acid 180 mg tablet
Drug: Matching placebo tablet

Registration Number: NCT02993406

Lead Sponsor: Esperion Therapeutics, Inc.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13970

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bempedoic Acid 180 mg	Bempedoic acid 180 mg tablet	Bempedoic acid 180 mg tablet taken orally, once daily.
Placebo Comparator	Matching placebo tablet	Matching placebo tablet taken orally, once daily

Primary Outcome Measures

Name	Time	Method
Number of Participants With First Occurrence of Four Component Major Adverse Cardiovascular Events (MACE)	Up to 68 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Time to First Occurrence of Coronary Revascularization	Up to 68 months	Number of participants with time to first occurrence of coronary revascularization are presented.
Number of Participants With First Occurrence of Myocardial Infarction	Up to 68 months	Number of participants with time to first occurrence of fatal and non-fatal myocardial infarction are presented.
Number of Participants With First Occurrence of Three Component MACE	Up to 68 months	The first key secondary end point was a three-component MACE, defined as death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
Number of Participants With Time to Cardiovascular Death	Up to 68 months	Number of participants with time to cardiovascular death are presented.
Number of Participants With Time to All-cause Mortality	Up to 68 months	All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.
Number of Participants With Time to First Occurrence of Stroke	Up to 68 months	Number of participants with time to first occurrence of fatal and non-fatal stroke.