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

Study Overview
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Brief Summary
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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.

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 a History of Statin Intolerance

Conditions
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Hypercholesterolemia

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


Participation Criteria
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Eligibility Criteria
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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

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<br>ETC-1002 treatment, once daily oral | Drug: ETC-1002<br>* 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<br>|
| Placebo Comparator: Placebo<br>Placebo treatment, once daily oral | Drug: Placebo<br>* Placebo once daily for 8 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lipid-lowering drugs, statin intolerance