Hypercholesterolemia Clinical Trial
— CLEAR WisdomOfficial 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
Verified date | April 2020 |
Source | Esperion Therapeutics |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 779 |
Est. completion date | August 22, 2018 |
Est. primary completion date | August 22, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Esperion Therapeutics |
United States,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. Review. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Percent Change From Baseline to Week 12 in Triglycerides (TGs) | 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 | |
Other | Percent Change From Baseline to Week 12 in HDL-C | 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 | |
Other | Percent Change From Baseline to Week 52 in 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 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 | |
Other | Percent Change From Baseline to Week 24 in 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 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 | |
Other | Percent Change From Baseline to Week 52 in 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 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 | |
Other | Percent Change From Baseline to Week 24 in 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 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 | |
Other | Percent Change From Baseline to Week 52 in 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 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 | |
Other | Percent Change From Baseline to Week 24 in Apo B | 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 | |
Other | Percent Change From Baseline to Week 52 in Apo B | 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 | |
Other | Percent Change From Baseline to Week 24 in hsCRP | 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 | |
Other | Percent Change From Baseline to Week 52 in hsCRP | 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 | |
Other | Change From Baseline to Week 52 in 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. 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 | |
Primary | Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | 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 | Percent Change From Baseline to Week 24 in LDL-C | 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 | |
Secondary | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | 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 | |
Secondary | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | 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 | |
Secondary | Percent Change From Baseline to Week 12 in Apolipoprotein b (Apo B) | 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 | |
Secondary | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | 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 | |
Secondary | Change From Baseline to Week 12 in LDL-C | 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 | |
Secondary | Change From Baseline to Week 24 in LDL-C | 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 |
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