A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides

A Placebo-Controlled, Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of ETC-1002 in Subjects With Hypercholesterolemia and Either Normal or Elevated Triglycerides.

This Phase 2 proof-of-concept study will assess the lipid regulating efficacy and safety of ETC-1002 in subjects with hypercholesterolemia and either normal or elevated triglycerides.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
  • California
    • Greenbrae, California, United States, 94904
    • Santa Rosa, California, United States, 95405
  • Florida
    • Jacksonville, Florida, United States, 32216
  • Illinois
    • Chicago, Illinois, United States, 60654
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Kentucky
    • Louisville, Kentucky, United States, 40213
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
  • Texas
    • Houston, Texas, United States, 77030
  • Virginia
    • Richmond, Virginia, United States, 23294

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

Major Inclusion Criteria:

• Provision of written informed consent prior to any study-specific procedure
• Fasting LDL-C between 130 and 220 mg/dL following wash-out of all lipid regulating medications and supplements
• Fasting triglyceride <400 mg/dL following wash-out of all lipid regulating medications and supplements
• BMI between 18 and 35 mg/kg2

Major Exclusion Criteria:

• Clinically significant cardiovascular disease, diabetes or uncontrolled hypertension
• Females of child bearing potential (i.e., females who are not surgically sterile or post-menopausal)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ETC-1002 120 mg (Group 1); Subjects with hypercholesterolemia and normal triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 80 mg (Group 2); Subjects with hypercholesterolemia and normal triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 40 mg (Group 3); Subjects with hypercholesterolemia and normal triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: Placebo (Group 4); Subjects with hypercholesterolemia and normal triglycerides	Drug: Placebo; Placebo daily for 12 weeks
Experimental: ETC-1002 120 mg (Group 5); Subjects with hypercholesterolemia and elevated triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 80 mg (Group 6); Subjects with hypercholesterolemia and elevated triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: ETC-1002 40 mg (Group 7); Subjects with hypercholesterolemia and elevated triglycerides	Drug: ETC-1002; ETC-1002 daily for 12 weeks
Experimental: Placebo (Group 8); Subjects with hypercholesterolemia and elevated triglycerides	Drug: Placebo; Placebo daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Week 12 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 mean of the values from Weeks -1 and 0. Least square (LS) mean percent change from Baseline to Week 12 was based on an analysis of covariance (ANCOVA) model with effects of treatment and triglyceride (TG) stratum and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum	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 mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and center and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Week 12 in TG	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 mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TG values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 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 mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 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 mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing non-HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)	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 mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TC values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)	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 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoB values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI)	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 mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoAI values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 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 mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing Lipoprotein (a) values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 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 mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing FFA values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 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 mean of the value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing hsCRP values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 in Total LDL Particles	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 mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Percent Change From Baseline to Week 12 in Total HDL Particles	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 mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).	Baseline; 12 weeks
Number of 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 12 weeks
Number of Participants With Clinically Significant Physical Examination Findings	Clinical significance was determined by the investigator.	up to 12 weeks
Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values	Clinical importance was determined by the investigator.	Baseline; up to 12 weeks
Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values	Clinical importance was determined by the investigator.	Baseline; up to 12 weeks
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12	Laboratory abnormalities are laboratory values that are outside the normal range.	Week 12

Collaborators and Investigators

• Sponsor: Esperion Therapeutics, Inc.

Publications and helpful links

General Publications

• Ballantyne CM, Davidson MH, Macdougall DE, Bays HE, Dicarlo LA, Rosenberg NL, Margulies J, Newton RS. Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. J Am Coll Cardiol. 2013 Sep 24;62(13):1154-62. doi: 10.1016/j.jacc.2013.05.050. Epub 2013 Jun 13.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): August 23, 2011
• Study Completion (Actual): August 23, 2011

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Actual): March 17, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia; 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: ETC-1002-003