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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: ETC-1002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |