Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: bempedoic acid 180mg; Other: placebo; Drug: evolocumab

• Registration Number: NCT03193047
• Lead Sponsor: Esperion Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-04-07
• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-20
• Primary Completion: 2018-01-29
• Study Completion: 2018-02-19
• Disposition First Submitted: 2018-04-30
• Disposition First Submitted QC: 2018-04-30
• Disposition First Posted: 2018-05-02
• Status Verified: 2020-03
• Results First Submitted: 2020-03-20
• Results First Submitted QC: 2020-03-20
• Last Update Submitted: 2020-03-20
• Results First Posted: 2020-04-03
• Last Update Posted: 2020-04-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
bempedoic acid	bempedoic acid 180mg	Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
placebo	placebo	Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
bempedoic acid	evolocumab	Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly
placebo	evolocumab	Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Month 2	Baseline; 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

Name	Time	Method
Absolute Change From Baseline in LDL-C at Month 1 and Month 2	Baseline; 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 LDL-C at Month 1	Baseline; 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.
Number of Participants With Any Treatment-emergent Adverse Event (AE) and Treatment-emergent Serious Adverse Event (SAE)	up to Month 2 (until 30 days after last dose)	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.
Percent Change From Baseline in Lipid Profile Parameters at Month 1 and Month 2	Baseline; 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.
Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3x the Upper Limit of Normal (ULN) at Month 1 and Month 2	Month 1 and Month 2	The number of participants with ALT or AST \>3x ULN was measured.
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Month 1 and Month 2	Baseline; 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.

Trial Locations

Locations (1)

L-MARC Research Center; 🇺🇸 Louisville, Kentucky, United States