Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C (CLEAR Tranquility)

NCT03001076 | Completed Phase 3 Results DMC

• 1 other identifier: 1002-048
• Study Type: interventional
• Target: 269
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if bempedoic acid (ETC-1002) added-on to ezetimibe therapy is effective and safe versus placebo in patients with elevated LDL cholesterol.

Conditions

Hypercholesterolemia; Atherosclerosis; Statin Adverse Reaction

Keywords

hyperlididemia; LDL; cholesterol; statin intolerance

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)

  Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for 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 was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline Value\]) multiplied by 100. Bempedoic Acid = BA. 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 as a fixed effects and Baseline as a covariate. In the ANCOVA model, missing LDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.

  Week 12

Secondary Outcomes (7)

• Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

  Week 12

• Percent Change From Baseline to Week 12 in Total Cholesterol (TC)

  Week 12

• Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)

  Week 12

• Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)

  Week 12

• Percent Change From Baseline to Week 12 in Triglycerides (TGs)

  Week 12

Other Outcomes (6)

• Percent Change From Baseline to Weeks 4 and 8 in LDL-C

  Week 4 and Week 8

• Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C

  Week 4 and Week 8

• Percent Change From Baseline to Weeks 4 and 8 in TC

  Week 4 and Week 8

Study Arms (2)

bempedoic acid

EXPERIMENTAL

bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)

Drug: Bempedoic acid; Drug: Ezetimibe

placebo

PLACEBO COMPARATOR

Matching placebo tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)

Drug: Ezetimibe; Other: Placebo

Interventions

Bempedoic acid DRUG

bempedoic acid 180 mg tablet

Also known as: ETC-1002

bempedoic acid

Ezetimibe DRUG

ezetimibe 10 mg tablet

Also known as: Zetia

bempedoic acid; placebo

Placebo OTHER

matching placebo tablet

Also known as: placebo control

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fasting LDL-cholesterol greater than or equal to 100 mg/dL at screening
• Men and nonpregnant, nonlactating women
• Use of stable lipid-modifying therapy for at least 4 weeks prior to screening that includes ezetimibe 10mg daily

You may not qualify if:

• Fasting blood triglycerides greater than or equal to 500 mg/dL
• Body Mass Index (BMI) greater than or equal to 50 kg/m2
• Recent history of clinically significant cardiovascular disease
• Use of statin therapy where doses are greater than those defined as "low-dose" within 4 weeks prior to screening; where "low-dose" is defined as an average daily dose of rosuvastatin 5 mg, atorvastatin 10 mg, simvastatin 10 mg, lovastatin 20 mg, pravastatin 40 mg, fluvastatin 40 mg, or pitavastatin 2 mg.

Sponsors & Collaborators

• Esperion Therapeutics, Inc.: lead

Study Sites (1)

Unknown Facility

Georgetown, Texas, 78626, United States

Location

Related Publications (8)

• 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.

  PMID: 27892461 BACKGROUND

• Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep. 2016 Oct;18(10):61. doi: 10.1007/s11883-016-0611-4.

  PMID: 27663902 BACKGROUND

• Thompson PD, MacDougall DE, Newton RS, Margulies JR, Hanselman JC, Orloff DG, McKenney JM, Ballantyne CM. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016 May-Jun;10(3):556-67. doi: 10.1016/j.jacl.2015.12.025. Epub 2016 Jan 6.

  PMID: 27206943 BACKGROUND

• Ballantyne CM, McKenney JM, MacDougall DE, Margulies JR, Robinson PL, Hanselman JC, Lalwani ND. Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy. Am J Cardiol. 2016 Jun 15;117(12):1928-33. doi: 10.1016/j.amjcard.2016.03.043. Epub 2016 Apr 6.

  PMID: 27138185 BACKGROUND

• Thompson PD, Rubino J, Janik MJ, MacDougall DE, McBride SJ, Margulies JR, Newton RS. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance. J Clin Lipidol. 2015 May-Jun;9(3):295-304. doi: 10.1016/j.jacl.2015.03.003. Epub 2015 Mar 19.

  PMID: 26073387 BACKGROUND

• Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, Hanselman JC, Zhao X, Leiter LA. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018 Oct;277:195-203. doi: 10.1016/j.atherosclerosis.2018.06.002. Epub 2018 Jun 12.

  PMID: 29910030 RESULT

• 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.

  PMID: 35916348 DERIVED

• 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.

  PMID: 32609313 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Atherosclerosis

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Esperion Therapeutics, Inc.

medinfo@esperion.com

1-833-377-7633

Study Officials

• Ron Haberman, MD

  Esperion Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: December 22, 2016
• Study Start: November 29, 2016
• Primary Completion: January 11, 2018
• Study Completion: February 12, 2018
• Last Updated: May 11, 2020
• Results First Posted: April 3, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)