A Study of the Efficacy and Safety of ETC-1002 in Participants With Statin Intolerance

A Placebo-Controlled, Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of ETC-1002 in Subjects With Hypercholesterolemia and a History of Statin Intolerance

This study will assess the Low-Density Lipoprotein-Cholesterol (LDL-C) lowering efficacy and safety of ETC-1002 versus placebo in participants with hypercholesterolemia and a history of statin intolerance.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo; Drug: ETC-1002

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
  • Indiana
    • Indianapolis, Indiana, United States, 46260
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
    • Wilmington, North Carolina, United States, 28401
  • Tennessee
    • Knoxville, Tennessee, United States, 37912

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• A history of statin intolerance that began during statin treatment and resolved within 4 weeks of stopping the statin treatment
• For participants on current lipid-regulating drugs - LDL-C 100-220 milligrams per deciliter (mg/dL) and triglycerides <350 mg/dL (prior to wash-out of all lipid-regulating drugs and supplements)
• For participants not on current lipid-regulating drugs - LDL-C 115-270 mg/dL and fasting TG <400 mg/dL

Key Exclusion Criteria:

• Acute significant cardiovascular disease
• Poorly controlled hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ETC-1002; ETC-1002 treatment, once daily oral	Drug: ETC-1002; Weeks 1-2, 60 milligrams per day (mg/day); Weeks 3-4, 120 mg/day; Weeks 5-6, 180 mg/day; Weeks 7-8, 240 mg/day
Placebo Comparator: Placebo; Placebo treatment, once daily oral	Drug: Placebo; Placebo once daily for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Week 8 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C)	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. Least square (LS) mean percent change from Baseline to Week 8 was based on an analysis of covariance (ANCOVA) model with effects of treatment and Baseline value as a covariate. Missing LDL-C values at Week 8 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Weeks 2, 4, 6, and 8 in Calculated LDL-C	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. A negative percent change from Baseline reflects clinical improvement.	Baseline; Weeks 2, 4, 6, and 8
Percent Change From Baseline to Week 8 in High-Density Lipoprotein-Cholesterol (HDL-C)	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Non-HDL-C	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Total Cholesterol	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Triglycerides	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Apolipoprotein B	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Apolipoprotein AI	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward). A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Lipoprotein (a)	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Data are based on the participant's last post-Baseline value. Only those participants having a valid assessment at Baseline and each subsequent time point were included in the summaries at that time point. Lipoprotein (a) results indicated as <3 in the laboratory data were set to 3 for purposes of analysis. A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in High-Sensitivity C-Reactive Protein (hsCRP)	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Data were based on the participant's last post-Baseline value. Only those participants having a valid assessment at Baseline and each subsequent time point were included in the summaries at that time point. hsCRP results indicated as <0.2 in the laboratory data were set to 0.2 for purposes of analysis. A negative percent change from Baseline reflects clinical improvement.	Baseline; 8 weeks
Percent Change From Baseline to Week 8 in Free Fatty Acids (FFA)	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 8 was based on an ANCOVA model with effects of treatment and Baseline value as a covariate. Data were based on the participant's last post-Baseline value.	Baseline; 8 weeks
Number of Participants Achieving Their National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) LDL-C Goal (<100 Milligrams Per Deciliter [mg/dL]) After 8 Weeks of Treatment	Participants were analyzed to evaluate the LDL-C target of <100 mg/dL for high risk participants with cardiovascular diseases. Missing values at Week 8 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; up to 8 weeks
Number or Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs were defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication.	up to 8 weeks
Number of Participants With Muscle-Related TEAEs	TEAEs were defined as AEs that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication.	up to 8 weeks

Collaborators and Investigators

• Sponsor: Esperion Therapeutics, Inc.
• Investigators: Study Director: Medical Director, Esperion Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 17, 2012
• First Posted (Estimate): December 18, 2012

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: statin intolerance; lipid-lowering drugs
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: 1002-006