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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hyperlipidemias

Intervention / Treatment
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* Combination Product: Bempedoic Acid + Ezetimibe Fixed-Dose Combination
* Drug: Bempedoic Acid
* Drug: Ezetimibe
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BA 180 mg + EZE 10 mg FDC<br>Bempedoic acid (BA) + ezetimibe (EZE) fixed-dose combination (FDC) 180 mg/10 mg tablets taken orally once daily for 12 weeks | Combination Product: Bempedoic Acid + Ezetimibe Fixed-Dose Combination<br>* bempedoic acid + ezetimibe FDC 180 mg/10 mg tablet<br>* Other names: ETC-1002 + Zetia;Drug: Placebos<br>* placebo tablet or capsule to match bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or bempedoic acid 180 mg tablet, or ezetimibe 10 mg capsule<br>* Other names: Placebo;|
| Experimental: BA 180 mg<br>Bempedoic acid (BA) 180 mg tablets taken orally once daily for 12 weeks | Drug: Bempedoic Acid<br>* bempedoic acid 180 mg tablet<br>* Other names: ETC-1002;Drug: Placebos<br>* placebo tablet or capsule to match bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or bempedoic acid 180 mg tablet, or ezetimibe 10 mg capsule<br>* Other names: Placebo;|
| Active Comparator: EZE 10 mg<br>Ezetimibe (EZE) 10 mg overencapsulated tablets taken orally once daily for 12 weeks | Drug: Ezetimibe<br>* ezetimibe 10 mg overencapsulated tablet<br>* Other names: Zetia;Drug: Placebos<br>* placebo tablet or capsule to match bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or bempedoic acid 180 mg tablet, or ezetimibe 10 mg capsule<br>* Other names: Placebo;|
| Placebo Comparator: Placebos<br>Placebos to match identical bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or identical bempedoic acid 180 mg tablet, or identical ezetimibe 10 mg capsule, taken orally, once daily for 12 weeks | Drug: Placebos<br>* placebo tablet or capsule to match bempedoic acid + ezetimibe fixed-dose combination (FDC) 180 mg/10 mg tablet, or bempedoic acid 180 mg tablet, or ezetimibe 10 mg capsule<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the LDL-C values from Week -2 and predose Day 1/Week 0. Percent change from baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group and randomization stratification as a factors and baseline LDL-C as a covariate. Percent change from baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. For LDL-C, if measured LDL-C value was available, measured LDL-C was used. | Baseline; Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the predose Day 1/Week 0 value. Percent change from baseline in hsCRP was analyzed using a non-parametric analysis. Percent change from baseline was calculated as: ([hsCRP value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the non-HDL-C values from Week -2 and predose Day 1/Week 0. Percent change from baseline in non-HDL-C was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline non-HDL-C as a covariate. Percent change from baseline was calculated as: ([non-HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the TC values from Week -2 and predose Day 1/Week 0. Percent change from baseline in TC was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline TC as a covariate. Percent change from baseline was calculated as: ([TC value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apo B. Baseline was defined as the predose Day 1/Week 0 value. Percent change from baseline in apo B was analyzed using ANCOVA with treatment group and randomization stratification as a factors and baseline apo B as a covariate. Percent change from baseline was calculated as: ([apo B value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was defined as the mean of the HDL-C values from Week -2 and predose Day 1/Week 0. Percent change from baseline was calculated as: ([HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. | Baseline; Week 12 | 
| Percent Change From Baseline to Week 12 in Triglycerides (TGs) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the mean of the TGs values from Week -2 and predose Day 1/Week 0. Percent change from baseline was calculated as: ([TGs value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. | Baseline; Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASCVD, hyperlipidemia, heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease, high cholesterol, HeFH, LDL