Assessment of the Long-Term Safety and Efficacy of Bempedoic Acid (CLEAR Harmony OLE)

• ClinicalTrials.gov Identifier: NCT03067441
• Recruitment Status: Completed
• First Posted: March 1, 2017
• Results First Posted: December 22, 2020
• Last Update Posted: March 1, 2021
• Sponsor: Esperion Therapeutics, Inc.
• Information provided by (Responsible Party): Esperion Therapeutics, Inc.

Study Description

Brief Summary:

The purpose of this study is to see if bempedoic acid (ETC-1002) is safe and well-tolerated in patients with high cardiovascular risk and elevated LDL cholesterol that is not adequately controlled by their current therapy.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1462 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Open-Label Extension (OLE) Study To Assess The Long-Term Safety and Efficacy of Bempedoic Acid (ETC-1002) 180 MG
• Actual Study Start Date: February 3, 2017
• Actual Primary Completion Date: November 5, 2019
• Actual Study Completion Date: November 5, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Open-Label bempedoic acid; bempedoic acid 180 mg tablet	Drug: bempedoic acid; bempedoic acid 180 mg tablets taken orally, once per day.; Other Name: ETC-1002

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Week 82 ]
   TEAEs are defined as adverse events that began or worsened in severity after the first dose of investigational medicinal product (IMP) until 30 days after the last dose in the Open-Label Extension (OLE) Study.

Secondary Outcome Measures :

1. Percent Change From Parent Study Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: LDL-C value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
2. Mean Change From Parent Study Baseline in LDL-C at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Mean change from Baseline was calculated as: Mean LDL-C value at Week 52/Week 78 minus Mean Parent Study Baseline value. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
3. Percent Change From Parent Study Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 72 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: non-HDL-C value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
4. Percent Change From Parent Study Baseline in Total Cholesterol at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Total cholesterol value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
5. Percent Change From Parent Study Baseline in Apolipoprotein B (ApoB) at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: ApoB value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
6. Percent Change From Parent Study Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: hs-CRP value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
7. Percent Change From Parent Study Baseline in Triglycerides at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Triglycerides value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
8. Percent Change From Parent Study Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: HDL-C value at Week 52/Week 78 minus Parent Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the mean of the values at screening and predose Day 1/Week 0 (Visit T1) in the Parent Study.
9. Percent Change From Open-Label Extension (OLE) Study Baseline in LDL-C at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
   Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: LDL-C value at Week 52/Week 78 minus OLE Study Baseline value divided by Parent Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
10. Mean Change From OLE Baseline in LDL-C at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 72 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Mean change from Baseline was calculated as: Mean LDL-C value at Week 52/Week 78 minus Mean OLE Study Baseline value. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
11. Percent Change From OLE Baseline in Non-HDL-C at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: non-HDL-C value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
12. Percent Change From OLE Baseline in Total Cholesterol at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Total Cholesterol value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
13. Percent Change From OLE Baseline ApoB at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: ApoB value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
14. Percent Change From OLE Baseline in Hs-CRP at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: hs-CRP value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
15. Percent Change From OLE Baseline in Triglycerides at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: Triglycerides value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.
16. Percent Change From OLE Baseline in HDL-C at Weeks 52 and 78 [ Time Frame: Baseline; Week 52 and Week 78 ]
    Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Percent change from Baseline was calculated as: HDL-C value at Week 52/Week 78 minus OLE Study Baseline value divided by OLE Study Baseline value multiplied by 100. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Successfully completed CLEAR Harmony (1002-040) parent study

Exclusion Criteria:

• Experienced a treatment-related SAE that led to study drug discontinuation in the CLEAR Harmony (1002-040) parent study.
• Medical condition requires lipid measurement and/or adjustment of background lipid-regulating therapy.

Contacts and Locations

Locations

United States, Florida

Jedidiah Clinical Research

Tampa, Florida, United States, 33607

United States, Kentucky

L-MARC Research Center

Louisville, Kentucky, United States, 40213

United States, Ohio

Sentral Clinical Research Services

Cincinnati, Ohio, United States, 45236

Sponsors and Collaborators

Esperion Therapeutics, Inc.

Investigators

• Study Director: Medical Director; Esperion Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Esperion Therapeutics, Inc.:

Study Protocol  [PDF] January 15, 2018

Statistical Analysis Plan  [PDF] December 5, 2019

More Information

Additional Information:

World Health Organization Fact Sheet No. 317 

Familial Hypercholesterolemia Foundation 

National Organization for Rare Disorders - Familial Hypercholesterolemia 

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.

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, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty PM, Cromwell WC, Ross JL, Ziajka PE; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun;5(3 Suppl):S1-8. doi: 10.1016/j.jacl.2011.04.003. Epub 2011 Apr 12.

Pollex RL, Joy TR, Hegele RA. Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81. doi: 10.1517/14728214.13.2.363.

Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W; Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001 Sep 4;104(10):1108-13. doi: 10.1161/hc3501.095214.

• Responsible Party: Esperion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03067441
• Other Study ID Numbers: 1002-050; 2016-004115-12 ( EudraCT Number )
• First Posted: March 1, 2017
• Results First Posted: December 22, 2020
• Last Update Posted: March 1, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Esperion Therapeutics, Inc.:

hyperlipidemia; cholesterol; heterozygous familial hypercholesterolemia; atherosclerotic cardiovascular disease; ASCVD; HeFH; LDL

Additional relevant MeSH terms:

Cardiovascular Diseases; Atherosclerosis; Hypercholesterolemia; Hyperlipidemias; 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