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

Hypercholesterolemia Clinical Trial

Official title:

A Multicenter Open-Label Extension (OLE) Study To Assess The Long-Term Safety and Efficacy of Bempedoic Acid (ETC-1002) 180 MG

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03067441
• Other study ID #: 1002-050
• Secondary ID: 2016-004115-12
• Status: Completed
• Phase: Phase 3
• Start date: February 3, 2017
• Est. completion date: November 5, 2019

Study information

• Verified date: February 2021
• Source: Esperion Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1462
• Est. completion date: November 5, 2019
• Est. primary completion date: November 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• Hypercholesterolemia

Intervention

Drug:
• bempedoic acid
bempedoic acid 180 mg tablets taken orally, once per day.

Locations

Country	Name	City	State
United States	Sentral Clinical Research Services	Cincinnati	Ohio
United States	L-MARC Research Center	Louisville	Kentucky
United States	Jedidiah Clinical Research	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Esperion Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — 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

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 . Review. — View Citation

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. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	Up to Week 82
Secondary	Percent Change From Parent Study Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Mean Change From Parent Study Baseline in LDL-C at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From Parent Study Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 52 and 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 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.	Baseline; Week 52 and Week 72
Secondary	Percent Change From Parent Study Baseline in Total Cholesterol at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From Parent Study Baseline in Apolipoprotein B (ApoB) at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From Parent Study Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From Parent Study Baseline in Triglycerides at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From Parent Study Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From Open-Label Extension (OLE) Study Baseline in LDL-C at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Mean Change From OLE Baseline in LDL-C at Weeks 52 and 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 OLE Study Baseline value. Baseline was defined as the last non-missing record prior to treatment start in the OLE Study.	Baseline; Week 52 and Week 72
Secondary	Percent Change From OLE Baseline in Non-HDL-C at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From OLE Baseline in Total Cholesterol at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From OLE Baseline ApoB at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From OLE Baseline in Hs-CRP at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From OLE Baseline in Triglycerides at Weeks 52 and 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.	Baseline; Week 52 and Week 78
Secondary	Percent Change From OLE Baseline in HDL-C at Weeks 52 and 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.	Baseline; Week 52 and Week 78

External Links

•   CLEAR Harmony - Reference to the Parent Study (NCT02666664)
•   Contact Esperion
•   Familial Hypercholesterolemia Foundation
•   National Organization for Rare Disorders - Familial Hypercholesterolemia
•   World Health Organization Fact Sheet No. 317