- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03001076
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)
April 24, 2020 updated by: Esperion Therapeutics, Inc.
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC 1002) 180 mg/Day as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
269
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
Georgetown, Texas, United States, 78626
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: bempedoic acid
bempedoic acid 180 mg tablet taken orally, daily.
Patients remain on ongoing ezetimibe therapy (study provided)
|
bempedoic acid 180 mg tablet
Other Names:
ezetimibe 10 mg tablet
Other Names:
|
Placebo Comparator: placebo
Matching placebo tablet taken orally, daily.
Patients remain on ongoing ezetimibe therapy (study provided)
|
matching placebo tablet
Other Names:
ezetimibe 10 mg tablet
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
Time Frame: Week 12
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed for non-HDL-C.
Baseline was defined as the mean of the non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: ([non-HDL-C value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Percent change from Baseline in non-HDL-C was analyzed using an 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 non-HDL-C data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
|
Week 12
|
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed for TC.
Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: ([TC value at Week 12 minus Baseline value] divided by [Baseline Value]) multiplied by 100.
Percent change from Baseline in TC was analyzed using an 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 TC data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
|
Week 12
|
Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed for apoB.
Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: [(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in apoB was analyzed using an 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 apoB data at Week 12 were imputed using multiple imputation method taking into account adherence to treatment.
|
Week 12
|
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed for hsCRP.
Baseline was defined as the last non-missing value on or prior to Day 1. Percent change from baseline was calculated as: [(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
|
Week 12
|
Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analyzed for TGs.
Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to D 1. Percent change from baseline was calculated as: [(TGs value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 12
|
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
Time Frame: Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analyzed for HDL-C.
Baseline was defined as the mean of the HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 12
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to approximately 16 weeks
|
TEAEs, defined as an adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and prior to the last dose of double-blind study drug + 30 days, were collected and reported.
|
Up to approximately 16 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Weeks 4 and 8 in LDL-C
Time Frame: Week 4 and Week 8
|
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 4 or 8 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in LDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 4 and Week 8
|
Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C
Time Frame: Week 4 and Week 8
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analyzed for Non-HDL-C.
Baseline was defined as the mean of the Non-HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(Non-HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in non-HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 4 and Week 8
|
Percent Change From Baseline to Weeks 4 and 8 in TC
Time Frame: Week 4 and Week 8
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analyzed for TC.
Baseline was defined as the mean of the TC values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(TC value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in TC was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 4 and Week 8
|
Percent Change From Baseline to Weeks 4 and 8 in TGs
Time Frame: Week 4 and Week 8
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed for TGs.
Baseline was defined as the mean of the TGs values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(TGs value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in TGs was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 4 and Week 8
|
Percent Change From Baseline to Weeks 4 and 8 in HDL-C
Time Frame: Week 4 and Week 8
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed for HDL-C.
Baseline was defined as the mean of the HDL-C values from the last two non-missing values on or prior to Day 1. Percent change from baseline was calculated as: [(HDL-C value at Week 4 or 8 minus Baseline value) divided by (Baseline Value)] multiplied by 100.
Percent change from Baseline in HDL-C was analyzed using an ANCOVA model with percent change from Baseline as the dependent variable, treatment as a fixed effects and Baseline as a covariate.
|
Week 4 and Week 8
|
Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C
Time Frame: Week 4, Week 8 and Week 12
|
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals.
Samples were collected and analysed 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. Absolute change from baseline was calculated as: LDL-C value at Week 4, 8, or 12 minus Baseline value.
|
Week 4, Week 8 and Week 12
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 29, 2016
Primary Completion (Actual)
January 11, 2018
Study Completion (Actual)
February 12, 2018
Study Registration Dates
First Submitted
December 20, 2016
First Submitted That Met QC Criteria
December 20, 2016
First Posted (Estimate)
December 22, 2016
Study Record Updates
Last Update Posted (Actual)
May 11, 2020
Last Update Submitted That Met QC Criteria
April 24, 2020
Last Verified
April 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Hypercholesterolemia
- Atherosclerosis
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Ezetimibe
- 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Other Study ID Numbers
- 1002-048
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atherosclerosis
-
University Hospital, CaenUnknownPeripheral Arterial Disease | Atherosclerosis Obliterans | Atherosclerosis Right Leg | Atherosclerosis Left LegFrance
-
Nantes University HospitalAbbottCompletedAtherosclerosis ObliteransFrance
-
Central Hospital, Nancy, FranceSuspended
-
Federal University of São PauloCompletedAtherosclerosis of ArteryBrazil
-
MedtronicActive, not recruitingAtherosclerosis of Femoral Artery | Obstructive Disease | Atherosclerosis of Popliteal ArteryFrance
-
Cabinet de Medecine Interne Générale Demetrio PitarchCompletedAtherosclerosis of Artery
-
Emory UniversityThe Robert W. Woodruff FoundationCompleted
-
Korea UniversityMinistry of Health & Welfare, KoreaCompletedAtherosclerosis | Noninvasive Imaging of AtherosclerosisKorea, Republic of
-
Zhejiang Zylox Medical Device Co., Ltd.RecruitingAtherosclerosis of Femoral ArteryGermany
-
VA Office of Research and DevelopmentCompletedSaphenous Vein Graft AtherosclerosisUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States