Back to resultsEvaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C (CLEAR Tranquility)
Primary Purpose
Hypercholesterolemia, Atherosclerosis, Statin Adverse Reaction
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Bempedoic acid
Ezetimibe
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia focused on measuring hyperlididemia, LDL, cholesterol, statin intolerance
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
bempedoic acid
placebo
Arm Description
bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)
Matching placebo tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
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.
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
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.
Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
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.
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
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.
Percent Change From Baseline to Week 12 in Triglycerides (TGs)
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.
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Full Information
NCT ID
NCT03001076
First Posted
December 20, 2016
Last Updated
April 24, 2020
Sponsor
Esperion Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03001076
Brief Title
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)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
November 29, 2016 (Actual)
Primary Completion Date
January 11, 2018 (Actual)
Study Completion Date
February 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Esperion Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia, Atherosclerosis, Statin Adverse Reaction
Keywords
hyperlididemia, LDL, cholesterol, statin intolerance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
269 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bempedoic acid
Arm Type
Experimental
Arm Description
bempedoic acid 180 mg tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo tablet taken orally, daily. Patients remain on ongoing ezetimibe therapy (study provided)
Intervention Type
Drug
Intervention Name(s)
Bempedoic acid
Other Intervention Name(s)
ETC-1002
Intervention Description
bempedoic acid 180 mg tablet
Intervention Type
Drug
Intervention Name(s)
Ezetimibe
Other Intervention Name(s)
Zetia
Intervention Description
ezetimibe 10 mg tablet
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo control
Intervention Description
matching placebo tablet
Primary Outcome Measure Information:
Title
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
Description
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.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Description
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.
Time Frame
Week 12
Title
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Description
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.
Time Frame
Week 12
Title
Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
Description
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.
Time Frame
Week 12
Title
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Description
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.
Time Frame
Week 12
Title
Percent Change From Baseline to Week 12 in Triglycerides (TGs)
Description
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.
Time Frame
Week 12
Title
Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C)
Description
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.
Time Frame
Week 12
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Up to approximately 16 weeks
Other Pre-specified Outcome Measures:
Title
Percent Change From Baseline to Weeks 4 and 8 in LDL-C
Description
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.
Time Frame
Week 4 and Week 8
Title
Percent Change From Baseline to Weeks 4 and 8 in Non-HDL-C
Description
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.
Time Frame
Week 4 and Week 8
Title
Percent Change From Baseline to Weeks 4 and 8 in TC
Description
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.
Time Frame
Week 4 and Week 8
Title
Percent Change From Baseline to Weeks 4 and 8 in TGs
Description
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.
Time Frame
Week 4 and Week 8
Title
Percent Change From Baseline to Weeks 4 and 8 in HDL-C
Description
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.
Time Frame
Week 4 and Week 8
Title
Absolute Change From Baseline to Weeks 4, 8, and 12 in LDL-C
Description
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.
Time Frame
Week 4, Week 8 and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ron Haberman, MD
Organizational Affiliation
Esperion Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
City
Georgetown
State/Province
Texas
ZIP/Postal Code
78626
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27892461
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.
Results Reference
background
PubMed Identifier
27663902
Citation
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.
Results Reference
background
PubMed Identifier
27206943
Citation
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.
Results Reference
background
PubMed Identifier
27138185
Citation
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.
Results Reference
background
PubMed Identifier
26073387
Citation
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.
Results Reference
background
PubMed Identifier
29910030
Citation
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.
Results Reference
result
PubMed Identifier
35916348
Citation
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.
Results Reference
derived
PubMed Identifier
32609313
Citation
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.
Results Reference
derived
Learn more about this trial
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)
We'll reach out to this number within 24 hrs