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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02991118
Recruitment Status : Completed
First Posted : December 13, 2016
Results First Posted : April 27, 2020
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
Esperion Therapeutics

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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Atherosclerotic Cardiovascular Disease Drug: bempedoic acid Drug: placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 779 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk Not Adequately Controlled by Their Lipid-Modifying Therapy
Actual Study Start Date : November 18, 2016
Actual Primary Completion Date : August 22, 2018
Actual Study Completion Date : August 22, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: bempedoic acid
bempedoic acid 180 mg/day
Drug: bempedoic acid
bempedoic acid 180 mg tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)
Other Name: ETC-1002

Placebo Comparator: Placebo
Placebo control
Drug: placebo
Matching placebo tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)
Other Name: placebo control




Primary Outcome Measures :
  1. Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: 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 :
  1. Percent Change From Baseline to Week 24 in LDL-C [ Time Frame: 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.

  2. Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [ Time Frame: 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.

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

  4. Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B) [ Time Frame: 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.

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

  6. Change From Baseline to Week 12 in LDL-C [ Time Frame: 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.

  7. Change From Baseline to Week 24 in LDL-C [ Time Frame: 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.


Other Outcome Measures:
  1. Percent Change From Baseline to Week 12 in Triglycerides (TGs) [ Time Frame: Baseline; Week 12 ]
    Baseline is defined as the mean of the TG 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 TG 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.

  2. Percent Change From Baseline to Week 12 in HDL-C [ Time Frame: Baseline; Week 12 ]
    Baseline is 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 is calculated as ([post-baseline value 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, cardiovascular risk (ASCVD and HeFH) crossed with Baseline statin intensity (low/moderate and high) as fixed effects and Baseline as a covariate.

  3. Percent Change From Baseline to Week 52 in LDL-C [ Time Frame: Baseline; Week 52 ]
    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 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.

  4. Percent Change From Baseline to Week 24 in Non-HDL-C [ Time Frame: Baseline; Week 24 ]
    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 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.

  5. Percent Change From Baseline to Week 52 in Non-HDL-C [ Time Frame: Baseline; Week 52 ]
    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 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.

  6. Percent Change From Baseline to Week 24 in TC [ Time Frame: Baseline; Week 24 ]
    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 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.

  7. Percent Change From Baseline to Week 52 in TC [ Time Frame: Baseline; Week 52 ]
    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 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.

  8. Percent Change From Baseline to Week 24 in Apo B [ Time Frame: Baseline; Week 24 ]
    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.

  9. Percent Change From Baseline to Week 52 in Apo B [ Time Frame: Baseline; Week 52 ]
    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.

  10. Percent Change From Baseline to Week 24 in hsCRP [ Time Frame: Baseline; Week 24 ]
    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.

  11. Percent Change From Baseline to Week 52 in hsCRP [ Time Frame: Baseline; Week 52 ]
    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.

  12. Change From Baseline to Week 52 in LDL-C [ Time Frame: Baseline; Week 52 ]
    Baseline was 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 in LDL-C was analyzed using an ANCOVA model with 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.



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-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

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): NCT02991118


Locations
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United States, Florida
Clearwater, Florida, United States
United States, Texas
Georgetown, Texas, United States
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] May 9, 2017
Statistical Analysis Plan  [PDF] June 14, 2018


Additional Information:
Publications:
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396.

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Responsible Party: Esperion Therapeutics
ClinicalTrials.gov Identifier: NCT02991118    
Other Study ID Numbers: 1002-047
2016-003486-26 ( EudraCT Number )
First Posted: December 13, 2016    Key Record Dates
Results First Posted: April 27, 2020
Last Update Posted: April 27, 2020
Last Verified: April 2020
Keywords provided by Esperion Therapeutics:
hyperlipidemia
cholesterol
familial hypercholesterolemia
atherosclerotic cardiovascular disease
ASCVD
HeFH
LDL
Additional relevant MeSH terms:
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Atherosclerosis
Hypercholesterolemia
Hyperlipidemias
Hyperlipoproteinemias
Cardiovascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs