Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C (CLEAR Tranquility)

Study Overview
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Brief Summary
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The purpose of this study is to determine if bempedoic acid (ETC-1002) added-on to ezetimibe therapy is effective and safe versus placebo in patients with elevated LDL cholesterol.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC 1002) 180 mg/Day as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C

Conditions
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Statin Adverse Reaction, Hypercholesterolemia, Atherosclerosis

Intervention / Treatment
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* Drug: Bempedoic acid
* Drug: Ezetimibe
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fasting LDL-cholesterol greater than or equal to 100 mg/dL at screening Men and nonpregnant, nonlactating women Use of stable lipid-modifying therapy for at least 4 weeks prior to screening that includes ezetimibe 10mg daily Exclusion Criteria: Fasting blood triglycerides greater than or equal to 500 mg/dL Body Mass Index (BMI) greater than or equal to 50 kg/m2 Recent history of clinically significant cardiovascular disease Use of statin therapy where doses are greater than those defined as low-dose within 4 weeks prior to screening; where low-dose is defined as 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.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bempedoic acid<br>bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided) | Drug: Bempedoic acid<br>* bempedoic acid 180 mg tablet<br>* Other names: ETC-1002;Drug: Ezetimibe<br>* ezetimibe 10 mg tablet<br>* Other names: Zetia;|
| Placebo Comparator: placebo<br>Matching placebo tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided) | Drug: Ezetimibe<br>* ezetimibe 10 mg tablet<br>* Other names: Zetia;Other: Placebo<br>* matching placebo tablet<br>* Other names: placebo control;|

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 the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: ([LDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100. Bempedoic Acid = BA. 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 as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 analysed for non-HDL-C. Baseline was 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 was calculated as: ([non-HDL-C value at Week 12 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 as a 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. | 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 analysed for TC. Baseline was 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 was calculated as: ([TC value at Week 12 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 as a 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. | Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for apoB. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: [(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Percent change from Baseline in apoB was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing apoB data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment. | Week 12 | 
| 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 analysed for hsCRP. Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: [(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. | 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 the last two non-missing values on or prior to D 1. Percent change from baseline was calculated as: [(TGs value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. | 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 the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100. Percent change from Baseline in HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate. | Week 12 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs, defined as an adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and prior to the last dose of double-blind study drug + 30 days, were collected and reported. | Up to approximately 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL, hyperlididemia, cholesterol, statin intolerance