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

• ClinicalTrials.gov Identifier: NCT02988115
• Recruitment Status: Completed
• First Posted: December 9, 2016
• Results First Posted: April 3, 2020
• Last Update Posted: April 3, 2020
• Sponsor: Esperion Therapeutics, Inc.
• Information provided by (Responsible Party): Esperion Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 7, 2016
• First Posted Date: December 9, 2016
• Results First Submitted Date: March 20, 2020
• Results First Posted Date: April 3, 2020
• Last Update Posted Date: April 3, 2020
• Actual Study Start Date: November 16, 2016
• Actual Primary Completion Date: March 16, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 20, 2020)

Percent Change From Baseline (PCFB) in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline; 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.

• Original Primary Outcome Measures (submitted: December 7, 2016): Percent change in low-density lipoprotein cholesterol (LDL-C) [ Time Frame: Baseline through 12 weeks ]

Current Secondary Outcome Measures (submitted: March 20, 2020)

• Percent Change From Baseline in LDL-C at Week 24 [ Time Frame: Baseline; 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.
• Percent Change From Baseline in the Lipid Profile at Week 12 [ Time Frame: Baseline; 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.
• Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) at Week 12 [ Time Frame: Baseline; 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.
• Absolute Change From Baseline in LDL-C at Week 12 and Week 24 [ Time Frame: Baseline; Week 12; 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Hypercholesterolemia
• Atherosclerotic Cardiovascular Disease
• Statin Adverse Reaction

Intervention

• Drug: bempedoic acid
  bempedoic acid 180 mg tablet
  Other Name: ETC-1002
• Other: placebo
  Matching placebo tablet
  Other Name: placebo control

Study Arms

• Experimental: bempedoic acid
  bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing lipid-modifying therapy (not study provided)
  Intervention: Drug: bempedoic acid
• Placebo Comparator: placebo
  Matching placebo tablet taken orally, daily. Patients remain on ongoing lipid-modifying therapy (not study provided)
  Intervention: Other: placebo

Publications *

• 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.
• 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.
• 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.
• 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. doi: 10.1056/NEJMoa042378.
• 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. doi: 10.1093/eurheartj/ehv182. Epub 2015 May 20.
• 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.
• Laufs U, Banach M, Mancini GBJ, Gaudet D, Bloedon LT, Sterling LR, Kelly S, Stroes ESG. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc. 2019 Apr 2;8(7):e011662. doi: 10.1161/JAHA.118.011662.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 6, 2017): 345
• Original Estimated Enrollment (submitted: December 7, 2016): 300
• Actual Study Completion Date: March 16, 2018
• Actual Primary Completion Date: March 16, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02988115
• Other Study ID Numbers: 1002-046
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Esperion Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Esperion Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ron Haberman, MD; Esperion Therapeutics, Inc.

• PRS Account: Esperion Therapeutics, Inc.
• Verification Date: March 2020