Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg, Ezetimibe 10mg, and Atorvastatin 20 mg Triplet Therapy in Patients With Elevated LDL-C
Primary Purpose
Hypercholesterolemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bempedoic acid 180mg
Ezetimibe 10mg
Atorvastatin 20mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia focused on measuring hyperlididemia, LDL, cholesterol
Eligibility Criteria
Inclusion Criteria:
- Fasting LDL-cholesterol between 130 - 189 mg/dL at screening following washout of all LDL-C-lowering drugs and nutritional supplements
- Men and nonpregnant, nonlactating women
- Sufficiently stable and suitable to undergo washout of all LDL-C-lowering drugs and nutritional supplements for 12 weeks
Exclusion Criteria:
- Fasting blood triglycerides greater than or equal to 400 mg/dL
- Body Mass Index (BMI) greater than 50 kg/m2
- History of clinically significant cardiovascular disease
- History of type 1 or type 2 diabetes
Sites / Locations
- PMG Research of Christie Clinic
- PMG Research of Cary
- PMG Research of Charlotte
- Sensenbrenner Primary Care
- PMG Research of Hickory
- PMG Research of Raleigh
- PMG Research of Rocky Mount
- PMG Research Salisbury
- PMG Research of Wilmington
- PMG Research of Charleston
- Hampton Roads Center for Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Triplet Therapy
placebo
Arm Description
Bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg taken orally, daily.
Matching placebos taken orally, daily.
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6
Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Percent change from Baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing LDL-C values were imputed using last observation carried forward (LOCF), with only post-Baseline values carried forward. If LDL-C was measured (i.e., if TG was >400 mg/dL or LDL-C was <50 mg/dL), the measured values were used in the analysis.
Secondary Outcome Measures
Percent Change From Baseline in Lipid Profile Parameters at Week 6
Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Baseline apolipoprotein B (apoB) was measured only at predose/Day 1. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing values were imputed using LOCF, with only post-Baseline values carried forward. non-HDL-C, non-high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol.
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6
Percent change is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. If only one value is available either at Week -1 (Screening Visit 2) or Week 0 (Treatment Visit 1), then that value is used as Baseline. Missing values were imputed using LOCF, with only post-Baseline values carried forward.
Number of Participants With LDL-C <70 mg/dL at Week 6
Analysis was based on LOCF values. If LDL-C was measured (i.e., if TG was >400 mg/dL or LDL-C was <50 mg/dL), the measured values were used in the analysis.
Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6
If LDL-C was measured (i.e., if TG was >400 mg/dL or LDL-C was <50 mg/dL), the measured values were used in the analysis.
Full Information
NCT ID
NCT03051100
First Posted
February 9, 2017
Last Updated
March 20, 2020
Sponsor
Esperion Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03051100
Brief Title
Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg, Ezetimibe 10mg, and Atorvastatin 20 mg Triplet Therapy in Patients With Elevated LDL-C
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Triplet Therapy With Bempedoic Acid (ETC 1002) 180 mg, Ezetimibe 10 mg, and Atorvastatin 20 mg in Patients With Elevated LDL C
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
January 19, 2017 (Actual)
Primary Completion Date
June 1, 2017 (Actual)
Study Completion Date
July 5, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Esperion Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine if triplet therapy with bempedoic acid (ETC-1002) 180mg, ezetimibe 10mg, and atorvastatin 20mg 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
Keywords
hyperlididemia, LDL, cholesterol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Triplet Therapy
Arm Type
Experimental
Arm Description
Bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg taken orally, daily.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebos taken orally, daily.
Intervention Type
Drug
Intervention Name(s)
Bempedoic acid 180mg
Other Intervention Name(s)
ETC-1002
Intervention Description
bempedoic acid 180 mg
Intervention Type
Drug
Intervention Name(s)
Ezetimibe 10mg
Other Intervention Name(s)
Zetia
Intervention Description
ezetimibe 10 mg
Intervention Type
Drug
Intervention Name(s)
Atorvastatin 20mg
Other Intervention Name(s)
Lipitor
Intervention Description
atorvastatin 20 mg
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 6
Description
Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Percent change from Baseline in LDL-C was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing LDL-C values were imputed using last observation carried forward (LOCF), with only post-Baseline values carried forward. If LDL-C was measured (i.e., if TG was >400 mg/dL or LDL-C was <50 mg/dL), the measured values were used in the analysis.
Time Frame
Baseline; Week 6
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Lipid Profile Parameters at Week 6
Description
Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the mean of the values from Week -1 (Screening Visit 2) and predose Day 1/Week 0 (Treatment Visit 1). Baseline apolipoprotein B (apoB) was measured only at predose/Day 1. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA) with treatment group as a factor and Baseline value as a covariate. Missing values were imputed using LOCF, with only post-Baseline values carried forward. non-HDL-C, non-high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol.
Time Frame
Baseline; Week 6
Title
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 6
Description
Percent change is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline is defined as the predose Day 1/Week 0 (Treatment Visit 1) value. If only one value is available either at Week -1 (Screening Visit 2) or Week 0 (Treatment Visit 1), then that value is used as Baseline. Missing values were imputed using LOCF, with only post-Baseline values carried forward.
Time Frame
Baseline; Week 6
Title
Number of Participants With LDL-C <70 mg/dL at Week 6
Description
Analysis was based on LOCF values. If LDL-C was measured (i.e., if TG was >400 mg/dL or LDL-C was <50 mg/dL), the measured values were used in the analysis.
Time Frame
Week 6
Title
Number of Participants With LDL-C Reduction ≥50% From Baseline at Week 6
Description
If LDL-C was measured (i.e., if TG was >400 mg/dL or LDL-C was <50 mg/dL), the measured values were used in the analysis.
Time Frame
Baseline; Week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Fasting LDL-cholesterol between 130 - 189 mg/dL at screening following washout of all LDL-C-lowering drugs and nutritional supplements
Men and nonpregnant, nonlactating women
Sufficiently stable and suitable to undergo washout of all LDL-C-lowering drugs and nutritional supplements for 12 weeks
Exclusion Criteria:
Fasting blood triglycerides greater than or equal to 400 mg/dL
Body Mass Index (BMI) greater than 50 kg/m2
History of clinically significant cardiovascular disease
History of type 1 or type 2 diabetes
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:
Facility Name
PMG Research of Christie Clinic
City
Champaign
State/Province
Illinois
ZIP/Postal Code
61820
Country
United States
Facility Name
PMG Research of Cary
City
Cary
State/Province
North Carolina
ZIP/Postal Code
27518
Country
United States
Facility Name
PMG Research of Charlotte
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28209
Country
United States
Facility Name
Sensenbrenner Primary Care
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28277
Country
United States
Facility Name
PMG Research of Hickory
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28601
Country
United States
Facility Name
PMG Research of Raleigh
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
Facility Name
PMG Research of Rocky Mount
City
Rocky Mount
State/Province
North Carolina
ZIP/Postal Code
27804
Country
United States
Facility Name
PMG Research Salisbury
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
Facility Name
PMG Research of Wilmington
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
PMG Research of Charleston
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
Hampton Roads Center for Clinical Research
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23451
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
Learn more about this trial
Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg, Ezetimibe 10mg, and Atorvastatin 20 mg Triplet Therapy in Patients With Elevated LDL-C
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