Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk

Phase 3

Completed

• Conditions: Atherosclerotic Cardiovascular Disease; Hypercholesterolemia
• Interventions: Drug: placebo; Drug: bempedoic acid

• Registration Number: NCT02991118
• Lead Sponsor: Esperion Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-18
• Study First Submitted: 2016-12-09
• Study First Submitted QC: 2016-12-09
• Study First Posted: 2016-12-13
• Primary Completion: 2018-08-22
• Study Completion: 2018-08-22
• Disposition First Submitted: 2018-11-08
• Disposition First Submitted QC: 2018-11-08
• Disposition First Posted: 2018-11-13
• Results First Submitted: 2020-03-20
• Status Verified: 2020-04
• Results First Submitted QC: 2020-04-24
• Last Update Submitted: 2020-04-24
• Results First Posted: 2020-04-27
• Last Update Posted: 2020-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 779

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo control
bempedoic acid	bempedoic acid	bempedoic acid 180 mg/day

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)	Baseline; Week 12	Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (atherosclerotic cardiovascular diseases \[ASCVD\] and heterozygous familial hypercholesterolemia \[HeFH\]) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 are imputed using multiple imputation method taking into account adherence to treatment.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 24 in LDL-C	Baseline; Week 24	Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 24 were imputed using multiple imputation method taking into account adherence to treatment.
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Baseline; Week 12	Baseline is defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing non-HDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	Baseline; Week 12	Baseline is defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing TC data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B)	Baseline; Week 12	Baseline for apo B was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. Percent change from Baseline in apo B was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate. In the ANCOVA model, missing apo B data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)	Baseline; Week 12	Baseline for hsCRP was defined as the last non-missing value on or prior to Day 1. Percent change from Baseline is calculated as (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100.
Change From Baseline to Week 12 in LDL-C	Baseline; Week 12	Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data.
Change From Baseline to Week 24 in LDL-C	Baseline; Week 24	Baseline is defined as the mean of the LDL-C values from the last two non-missing values on or prior to Day 1. Change from Baseline is calculated as the post-baseline value minus the baseline value. Analysis was conducted using descriptive statistics by treatment group using observed data.