Evaluation of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients

Study Overview
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Brief Summary
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The purpose of this research study is to see how ETC-1002 is tolerated in the body, to measure the amount of ETC-1002 in the blood, and to determine how ETC-1002 affects the level of LDL-cholesterol (bad cholesterol) and other markers of health and disease in blood and urine in patients with elevated LDL-cholesterol with or without statin intolerance.

Detailed Description
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Hypercholesterolemic patients either with or without a history of statin intolerance (1:1 ratio) will be randomized to receive once daily by mouth capsules containing either ETC-1002, ezetimibe, or ETC-1002 + ezetimibe. This study will explore the safety and efficacy of concomitant administration of ETC-1002 and ezetimibe, while also exploring the effect of ezetimibe on ETC-1002 systemic exposure.

Official Title
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A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of ETC-1002, Ezetimibe, and the Combination in Hypercholesterolemic Patients With or Without Statin Intolerance

Conditions
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Hypercholesterolemia

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Statin intolerant and statin tolerant Fasting LDL-C between 130 mg/dL and 220 mg/dL Fasting triglyceride less than or equal to 400 mg/dL Body mass index (BMI) between 18 and 45 kg/m2 Key Exclusion Criteria: History or current clinically significant cardiovascular disease History or current type 1 diabetes or uncontrolled type 2 diabetes Use of metformin or thiazolidinediones (TZD) within 3 months of screening History of joint symptoms difficult to differentiate from myalgia Uncontrolled hypothyroidism Liver disease or dysfunction Renal dysfunction or nephritic syndrome Gastrointestinal (GI) conditions or prior GI procedures HIV or AIDS History or malignancy History or drug or alcohol abuse within last 2 years Use of experimental or investigational drugs within 30 days of screening Use of ETC-1002 in a previous clinical study

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/day<br>Orally, once daily in morning as capsules | Drug: ETC-1002<br>* Patients receive ETC-1002<br>|
| Experimental: ETC-1002 180 mg/day<br>Orally, once daily in morning as capsules | Drug: ETC-1002<br>* Patients receive ETC-1002<br>|
| Active Comparator: ezetimibe 10mg/day<br>Orally, once daily in morning as capsules | Drug: Ezetimibe<br>* Patients receive ezetimibe<br>* Other names: Zetia;|
| Experimental: ETC-1002 120 mg/day + ezetimibe 10mg/day<br>Orally, once daily in morning | Drug: ETC-1002<br>* Patients receive ETC-1002<br>Drug: Ezetimibe<br>* Patients receive ezetimibe<br>* Other names: Zetia;|
| Experimental: ETC-1002 180 mg/day + ezetimibe 10mg/day<br>Orally, once daily in morning | Drug: ETC-1002<br>* Patients receive ETC-1002<br>Drug: Ezetimibe<br>* Patients receive ezetimibe<br>* Other names: Zetia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in calculated low density lipoprotein-cholesterol (LDL-C) |  | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in other lipid measures non high density lipoprotein cholesterol (nonHDL-C) |  | Baseline and 12 weeks | 
| Safety using adverse event reports; vital signs |  | up to 21 weeks including screening | 
| Percent change in Apolipoprotein B (ApoB) |  | Baseline and 12 weeks | 
| Percent change in high sensitivity C-reactive protein (hsCRP) |  | Baseline and 12 weeks | 
| Safety using adverse event reports; clinical laboratory results |  | up to 21 weeks including screening | 
| Safety using adverse event reports; rates of muscle-related adverse |  | up to 21 weeks including screening | 

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