Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant

Hypercholesterolemia Clinical Trial

— CLEAR Serenity  

Official title:

A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180 mg Compared to Placebo Added to Background Lipid-Modifying Therapy in Patients With Elevated LDL-C Who Are Statin Intolerant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02988115
• Other study ID #: 1002-046
• Status: Completed
• Phase: Phase 3
• Start date: November 16, 2016
• Est. completion date: March 16, 2018

Study information

• Verified date: March 2020
• Source: Esperion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if bempedoic acid (ETC-1002) is effective and safe versus placebo in patients with elevated LDL cholesterol and who are statin-intolerant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 345
• Est. completion date: March 16, 2018
• Est. primary completion date: March 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Require lipid-modifying therapy for primary or secondary prevention of cardiovascular disease

• Fasting LDL-C =130 mg/dL for primary prevention or LDL-C =100 mg/dL for secondary prevention (history of HeFH and/or ASCVD)

• Be statin-intolerant (unable to tolerate 2 or more statins)

Exclusion Criteria:

• Total fasting triglyceride =500 mg/dL

• Renal dysfunction or nephrotic syndrome or history of nephritis

• Body Mass Index (BMI) =50 kg/m2

• Significant cardiovascular disease or cardiovascular event in the past 3 months

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• Hypercholesterolemia
• Hyperlipidemias
• Statin Adverse Reaction

Intervention

Drug:
• bempedoic acid
bempedoic acid 180 mg tablet

Other:
• placebo
Matching placebo tablet

Locations

Country	Name	City	State
United States	Site 1	Dallas	Texas
United States	Site 2	Dallas	Texas
United States	Site 1	Miami	Florida
United States	Site 2	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Esperion Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

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

Eckel RH. Approach to the patient who is intolerant of statin therapy. J Clin Endocrinol Metab. 2010 May;95(5):2015-22. doi: 10.1210/jc.2009-2689. — 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

Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6;352(1):20-8. — View Citation

Robinson JG, Stone NJ. The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk: a new paradigm supported by more evidence. Eur Heart J. 2015 Aug 14;36(31):2110-2118. Epub 2015 May 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline (PCFB) in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12	PCFB was calculated as the ([post-Baseline (BL) value minus the BL value] divided by the BL value ) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available, that single value was used as BL. PCFB in LDL-C was analyzed using analysis of covariance (ANCOVA), with treatment group and stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing lipid data at Week 12 who were no longer taking study treatment, missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking study treatment, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.	Baseline; Week 12
Secondary	Percent Change From Baseline in LDL-C at Week 24	PCFB was calculated as the ([post-BL value minus the BL value] divided by the BL value ) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available then that single value was used as BL. PCFB in LDL-C was analyzed using ANCOVA, with treatment group and stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing lipid data at Week 12 who were no longer taking study treatment, missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking study treatment, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.	Baseline; Week 24
Secondary	Percent Change From Baseline in the Lipid Profile at Week 12	PCFB was calculated as: ([post-BL value minus the BL value] divided by the BL value) x 100. BL was defined as the mean of the last two non-missing values on or prior to Day 1. If only one value was available, that single value was used as BL. apoB and TC BL were defined as the last non-missing value on/prior to Day 1. PCFB was analyzed using ANCOVA, with treatment and group stratification factor (primary prevention; secondary prevention) as fixed effects and BL as a covariate. For participants with missing data at Week 12 who were no longer taking study treatment (ST), missing values were imputed using multiple imputation via a regression-based model including stratification and BL data from placebo participants only. In this imputation model, treatment group was not included. For participants with missing lipid data at Week 12 who were still taking ST, missing values were imputed using multiple imputation via a regression-based model including treatment, stratification and BL value.	Baseline; Week 12
Secondary	Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline for hsCRP is defined as the last non-missing value on or prior to Day 1. Percent change from Baseline in hsCRP, non-parametric (Wilcoxon rank-sum test) analysis with Hodges-Lehmann estimates and confidence interval was performed.	Baseline; Week 12
Secondary	Absolute Change From Baseline in LDL-C at Week 12 and Week 24	Change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the mean of the last two non-missing values on or prior to Day 1.	Baseline; Week 12; Week 24

External Links

•   World Health Organization Fact Sheet No. 317