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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)

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ClinicalTrials.gov Identifier: NCT03001076
Recruitment Status : Completed
First Posted : December 22, 2016
Results First Posted : April 3, 2020
Last Update Posted : May 11, 2020
Sponsor:
Information provided by (Responsible Party):
Esperion Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Atherosclerosis Statin Adverse Reaction Drug: Bempedoic acid Drug: Ezetimibe Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 269 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 29, 2016
Actual Primary Completion Date : January 11, 2018
Actual Study Completion Date : February 12, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ezetimibe

Arm Intervention/treatment
Experimental: bempedoic acid
bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)
Drug: Bempedoic acid
bempedoic acid 180 mg tablet
Other Name: ETC-1002

Drug: Ezetimibe
ezetimibe 10 mg tablet
Other Name: Zetia

Placebo Comparator: placebo
Matching placebo tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)
Drug: Ezetimibe
ezetimibe 10 mg tablet
Other Name: Zetia

Other: Placebo
matching placebo tablet
Other Name: placebo control




Primary Outcome Measures :
  1. Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Week 12 ]
    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.


Secondary Outcome Measures :
  1. Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [ Time Frame: Week 12 ]
    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.

  2. Percent Change From Baseline to Week 12 in Total Cholesterol (TC) [ Time Frame: Week 12 ]
    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.

  3. Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) [ Time Frame: Week 12 ]
    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.

  4. Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) [ Time Frame: Week 12 ]
    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.

  5. Percent Change From Baseline to Week 12 in Triglycerides (TGs) [ Time Frame: Week 12 ]
    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.

  6. Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Week 12 ]
    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.

  7. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 16 weeks ]
    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.


Other Outcome Measures:
  1. Percent Change From Baseline to Weeks 4 and 8 in LDL-C [ Time Frame: Week 4 and Week 8 ]
    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 4 or 8 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 as a fixed effects and Baseline as a covariate.

  2. Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C [ Time Frame: Week 4 and Week 8 ]
    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 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 4 or 8 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.

  3. Percent Change From Baseline to Weeks 4 and 8 in TC [ Time Frame: Week 4 and Week 8 ]
    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 the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(TC value at Week 4 or 8 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.

  4. Percent Change From Baseline to Weeks 4 and 8 in TGs [ Time Frame: Week 4 and Week 8 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed for TGs. Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(TGs value at Week 4 or 8 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.

  5. Percent Change From Baseline to Weeks 4 and 8 in HDL-C [ Time Frame: Week 4 and Week 8 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed 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 4 or 8 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.

  6. Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C [ Time Frame: Week 4, Week 8 and Week 12 ]
    Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analysed 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. Absolute change from baseline was calculated as: LDL-C value at Week 4, 8, or 12 minus Baseline value.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03001076


Locations
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United States, Texas
Georgetown, Texas, United States, 78626
Sponsors and Collaborators
Esperion Therapeutics
Investigators
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Study Director: Ron Haberman, MD Esperion Therapeutics
  Study Documents (Full-Text)

Documents provided by Esperion Therapeutics:
Study Protocol  [PDF] February 10, 2017
Statistical Analysis Plan  [PDF] February 6, 2018

Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Esperion Therapeutics
ClinicalTrials.gov Identifier: NCT03001076    
Other Study ID Numbers: 1002-048
First Posted: December 22, 2016    Key Record Dates
Results First Posted: April 3, 2020
Last Update Posted: May 11, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Esperion Therapeutics:
hyperlididemia
LDL
cholesterol
statin intolerance
Additional relevant MeSH terms:
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Atherosclerosis
Hypercholesterolemia
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs