Evaluation of ETC-1002 in Participants With Hypercholesterolemia and Hypertension

Study Overview
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Brief Summary
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This Phase 2 study will assess the efficacy and safety of ETC-1002 monotherapy versus placebo in participants with hypercholesterolemia and hypertension.

Official Title
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A Placebo-Controlled, Randomized, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of ETC-1002 in Patients With Hypercholesterolemia and Hypertension

Conditions
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Hypercholesterolemia, Hypertension

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mean 24-hour ambulatory SBP greater than or equal to 130 mmHg or- Mean 24-hour ambulatory DBP greater than or equal to 80 mmHg Fasting LDL-C between 100 and 220 mg/dL Fasting triglycerides less than 400 mg/dL Body mass index (BMI) between 18 and 45 kg/m2 Exclusion Criteria: Known or suspected secondary hypertension or history of malignant hypertension Taking more than two anti-hypertension medications at the first visit History or current clinically significant cardiovascular disease History or current type 1 diabetes or type 2 diabetes

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 180 mg/day | Drug: ETC-1002<br>* ETC-1002 capsules taken once daily<br>|
| Placebo Comparator: Placebo<br>Placebo control | Drug: Placebo<br>* Placebo capsules taken once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6 | 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 -1 and Week 0. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. For the Week 6 endpoint, missing values at Week 6 were imputed using the last observation carried forward (LOCF) procedure, with only post-Baseline values carried forward. Modified Intent-to-Treat (mITT) Population is defined as all randomized participants who received at least 1 dose of study drug, had a Baseline assessment, and had at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of study drug | Baseline; 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in Mean Daytime SBP to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in Mean Daytime DBP to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in Mean Nighttime SBP to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in Mean Nighttime DBP to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in Sitting Cuff SBP to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value. | Baseline: 6 weeks | 
| Change From Baseline in Sitting Cuff DBP to Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6 | A non-parametric analysis was performed for hsCRP parameters. 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 last value prior to the first dose of study medication. If hsCRP was <0.2, 0.1 was imputed for analysis. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Percent Change From Baseline in Total Cholesterol to Week 6 | 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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and value as a covariate. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6 | 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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6 | 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 last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Percent Change From Baseline in Triglycerides (TG) to Week 6 | 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 -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value. Data was analyzed using non-parametric analysis. | Baseline; 6 weeks | 
| Percent Change From Baseline in HDL-C to Week 6 | 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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6 | 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 -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value. | Baseline; 6 weeks | 
| Change From Baseline in Body Weight to Week 6 | Baseline was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline; 6 weeks | 
| Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Plasma trough concentration is defined as the lowest concentration reached before the next dose is administered. | Week 2, Week 4 and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL, Cholesterol