- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02991118
Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk (CLEAR Wisdom)
April 24, 2020 updated by: Esperion Therapeutics, Inc.
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
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
779
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Florida
-
Clearwater, Florida, United States
-
-
Texas
-
Georgetown, Texas, United States
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Placebo control
|
Matching placebo tablet taken orally, once daily.
Patients remain on ongoing lipid-modifying therapy (not study provided)
Other Names:
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Experimental: bempedoic acid
bempedoic acid 180 mg/day
|
bempedoic acid 180 mg tablet taken orally, once daily.
Patients remain on ongoing lipid-modifying therapy (not study provided)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline; Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline; Week 24
|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 24
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 12
|
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.
|
Baseline; Week 52
|
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.
|
Baseline; Week 24
|
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.
|
Baseline; Week 52
|
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.
|
Baseline; Week 24
|
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.
|
Baseline; Week 52
|
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.
|
Baseline; Week 24
|
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.
|
Baseline; Week 52
|
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.
|
Baseline; Week 24
|
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.
|
Baseline; Week 52
|
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.
|
Baseline; Week 52
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.
- Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.
- 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. No abstract available. Erratum In: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Circulation. 2015 Dec 22;132(25):e396.
- Goldberg AC, Leiter LA, Stroes ESG, Baum SJ, Hanselman JC, Bloedon LT, Lalwani ND, Patel PM, Zhao X, Duell PB. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019 Nov 12;322(18):1780-1788. doi: 10.1001/jama.2019.16585. Erratum In: JAMA. 2020 Jan 21;323(3):282.
- Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3.
- Robinson JG. Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm. 2013 Mar;19(2):139-49. doi: 10.18553/jmcp.2013.19.2.139.
- Ballantyne CM, Bays HE, Louie MJ, Smart J, Zhang Y, Ray KK. Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid. J Am Heart Assoc. 2022 Aug 2;11(15):e024531. doi: 10.1161/JAHA.121.024531. Epub 2022 Aug 2.
- Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Flaim J, Ye Z, Catapano AL. Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia. JAMA Cardiol. 2020 Oct 1;5(10):1124-1135. doi: 10.1001/jamacardio.2020.2314.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 18, 2016
Primary Completion (Actual)
August 22, 2018
Study Completion (Actual)
August 22, 2018
Study Registration Dates
First Submitted
December 9, 2016
First Submitted That Met QC Criteria
December 9, 2016
First Posted (Estimate)
December 13, 2016
Study Record Updates
Last Update Posted (Actual)
April 27, 2020
Last Update Submitted That Met QC Criteria
April 24, 2020
Last Verified
April 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Vascular Diseases
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Lipid Metabolism Disorders
- Dyslipidemias
- Cardiovascular Diseases
- Hypercholesterolemia
- Atherosclerosis
- Hyperlipidemias
- Hyperlipoproteinemias
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Hypolipidemic Agents
- Lipid Regulating Agents
- 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Other Study ID Numbers
- 1002-047
- 2016-003486-26 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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