Back to resultsEvaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy
Primary Purpose
Hypercholesterolemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bempedoic acid 180mg
placebo
evolocumab
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia focused on measuring Cholesterol, PCSK9, Repatha, evolocumab, LDL-C
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years or legal age of majority depending on regional law
- Fasting, calculated LDL-C at screening ≥160 mg/dL and following PCSK9i therapy ≥70 mg/dL
- Men and nonpregnant, nonlactating women
Exclusion Criteria:
- Heterozygous (HeFH) or Homozygous (HoFH) Familial Hypercholesterolemia
- Total fasting TG ≥500 mg/dL
- Renal dysfunction or a glomerulonephropathy; eGFR <30 mL/min/1.73 m2
- Known cardiovascular disease (CVD), peripheral arterial disease (PAD), or cerebrovascular disease (CD)
- History of type 1 or type 2 diabetes
- Uncontrolled hypertension
- Uncontrolled hypothyroidism
- Liver disease or dysfunction
- Gastrointestinal conditions or procedures (including Lap-Band® or gastric bypass)
- History of hematologic or coagulation disorders
- History of malignancy (except non-metastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ)
- Unexplained creatine kinase (CK) >3 × ULN
- Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to screening, such as: anacetrapib, dalcetrapib, or evacetrapib
- Pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 30 days after the end of treatment
Sites / Locations
- L-MARC Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
bempedoic acid
placebo
Arm Description
Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Month 2
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 average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA), with treatment group as a factor and Baseline as a covariate. Missing data were imputed using last observation carried forward (LOCF) (only post-Baseline values were carried forward).
Secondary Outcome Measures
Percent Change From Baseline in LDL-C at Month 1
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 average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis.
Absolute Change From Baseline in LDL-C at Month 1 and Month 2
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the average of the Screening Visit 4 and the Day 1 value. If only 1 value is available, then that single value is used as Baseline. Change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF.
Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2
Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline apolipoprotein B (apoB) is defined as the Day 1 value. Baseline total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) are defined as the average of the Month -1 (Screening Visit 4) and the Day 1 (Treatment Visit 1) values. If a missing value presented at Month -1 or Day 1, then the last non-missing value prior to the first dose of double-blind study medication (including unscheduled assessments) within Month -1 and Day 1 was used to compute the Baseline measurements. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF.
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2
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 Day 1 value. Percent change from Baseline was analyzed using a non-parametric approach. Missing Month 2 data were handled by LOCF. Observed data were used for analysis at Month 1.
Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE)
Treatment-emergent AEs (TEAEs) and SAEs (TESAEs) were reported and defined as any AE that began or worsened after the first dose of investigational medicinal product.
Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3x the Upper Limit of Normal (ULN) at Month 1 and Month 2
The number of participants with ALT or AST >3x ULN was measured.
Full Information
NCT ID
NCT03193047
First Posted
June 19, 2017
Last Updated
March 20, 2020
Sponsor
Esperion Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03193047
Brief Title
Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy
Official Title
A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg QD When Added to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)-Inhibitor Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
April 7, 2017 (Actual)
Primary Completion Date
January 29, 2018 (Actual)
Study Completion Date
February 19, 2018 (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
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine if bempedoic acid (ETC-1002) 180mg added to PCSK9 inhibitor (evolocumab) therapy is effective and safe 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
Cholesterol, PCSK9, Repatha, evolocumab, LDL-C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bempedoic acid
Arm Type
Experimental
Arm Description
Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
Intervention Type
Drug
Intervention Name(s)
bempedoic acid 180mg
Other Intervention Name(s)
ETC-1002
Intervention Description
Daily bempedoic acid 180mg tablet in addition to monthly PCSK9i (evolocumab) background therapy
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Daily matching placebo tablet in addition to monthly PCSK9i (evolocumab) background therapy
Intervention Type
Drug
Intervention Name(s)
evolocumab
Other Intervention Name(s)
Repatha
Intervention Description
Monthly PCSK9i (evolocumab) background therapy
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Month 2
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 average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using analysis of covariance (ANCOVA), with treatment group as a factor and Baseline as a covariate. Missing data were imputed using last observation carried forward (LOCF) (only post-Baseline values were carried forward).
Time Frame
Baseline; Month 2
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in LDL-C at Month 1
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 average of the last two non-missing values within Month -1 (Screening Visit 4) and Day 1 (Treatment Visit 1) values (including unscheduled assessments). If only one value was available, then that single value was used at Baseline. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis.
Time Frame
Baseline; Month 1
Title
Absolute Change From Baseline in LDL-C at Month 1 and Month 2
Description
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the average of the Screening Visit 4 and the Day 1 value. If only 1 value is available, then that single value is used as Baseline. Change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF.
Time Frame
Baseline; Month 1 and Month 2
Title
Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2
Description
Percent change from Baseline is calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value ) x 100. Baseline apolipoprotein B (apoB) is defined as the Day 1 value. Baseline total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) are defined as the average of the Month -1 (Screening Visit 4) and the Day 1 (Treatment Visit 1) values. If a missing value presented at Month -1 or Day 1, then the last non-missing value prior to the first dose of double-blind study medication (including unscheduled assessments) within Month -1 and Day 1 was used to compute the Baseline measurements. Percent change from Baseline was analyzed using ANCOVA, with treatment group as a factor and Baseline as a covariate. Observed data were used for analysis at Month 1. Missing Month 2 data were handled by LOCF.
Time Frame
Baseline; Month 1 and Month 2
Title
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2
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 Day 1 value. Percent change from Baseline was analyzed using a non-parametric approach. Missing Month 2 data were handled by LOCF. Observed data were used for analysis at Month 1.
Time Frame
Baseline; Month 1 and Month 2
Title
Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE)
Description
Treatment-emergent AEs (TEAEs) and SAEs (TESAEs) were reported and defined as any AE that began or worsened after the first dose of investigational medicinal product.
Time Frame
up to Month 2 (until 30 days after last dose)
Title
Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3x the Upper Limit of Normal (ULN) at Month 1 and Month 2
Description
The number of participants with ALT or AST >3x ULN was measured.
Time Frame
Month 1 and Month 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years or legal age of majority depending on regional law
Fasting, calculated LDL-C at screening ≥160 mg/dL and following PCSK9i therapy ≥70 mg/dL
Men and nonpregnant, nonlactating women
Exclusion Criteria:
Heterozygous (HeFH) or Homozygous (HoFH) Familial Hypercholesterolemia
Total fasting TG ≥500 mg/dL
Renal dysfunction or a glomerulonephropathy; eGFR <30 mL/min/1.73 m2
Known cardiovascular disease (CVD), peripheral arterial disease (PAD), or cerebrovascular disease (CD)
History of type 1 or type 2 diabetes
Uncontrolled hypertension
Uncontrolled hypothyroidism
Liver disease or dysfunction
Gastrointestinal conditions or procedures (including Lap-Band® or gastric bypass)
History of hematologic or coagulation disorders
History of malignancy (except non-metastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ)
Unexplained creatine kinase (CK) >3 × ULN
Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to screening, such as: anacetrapib, dalcetrapib, or evacetrapib
Pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 30 days after the end of treatment
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
L-MARC Research Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40213
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
24222016
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. No abstract available. Erratum In: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Circulation. 2015 Dec 22;132(25):e396.
Results Reference
background
PubMed Identifier
11535564
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. doi: 10.1161/hc3501.095214.
Results Reference
background
PubMed Identifier
12672737
Citation
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. doi: 10.1001/jama.289.13.1681.
Results Reference
background
Links:
URL
http://www.who.int/mediacentre/factsheets/fs317/en/
Description
World Health Organization Fact Sheet No. 317
Learn more about this trial
Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy
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