A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides
- Registration Number
- NCT01262638
- Lead Sponsor
- Esperion Therapeutics, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 177
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ETC-1002 120 mg (Group 1) ETC-1002 Subjects with hypercholesterolemia and normal triglycerides ETC-1002 40 mg (Group 3) ETC-1002 Subjects with hypercholesterolemia and normal triglycerides ETC-1002 40 mg (Group 7) ETC-1002 Subjects with hypercholesterolemia and elevated triglycerides Placebo (Group 4) Placebo Subjects with hypercholesterolemia and normal triglycerides Placebo (Group 8) Placebo Subjects with hypercholesterolemia and elevated triglycerides ETC-1002 80 mg (Group 2) ETC-1002 Subjects with hypercholesterolemia and normal triglycerides ETC-1002 120 mg (Group 5) ETC-1002 Subjects with hypercholesterolemia and elevated triglycerides ETC-1002 80 mg (Group 6) ETC-1002 Subjects with hypercholesterolemia and elevated triglycerides
- Primary Outcome Measures
Name Time Method Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum Baseline; 12 weeks 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).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in Total LDL Particles Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in Non-HDL-C Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in Total Cholesterol (TC) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in TG Baseline; 12 weeks 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).
Percent Change From Baseline to Week 12 in Total HDL Particles Baseline; 12 weeks 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).
Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values Baseline; up to 12 weeks Clinical importance was determined by the investigator.
Percent Change From Baseline to Week 12 in Lipoprotein (a) Baseline; 12 weeks 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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) up to 12 weeks 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.
Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values Baseline; up to 12 weeks Clinical importance was determined by the investigator.
Number of Participants With Clinically Significant Physical Examination Findings up to 12 weeks Clinical significance was determined by the investigator.
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 Week 12 Laboratory abnormalities are laboratory values that are outside the normal range.