Evaluation of ETC-1002 vs Placebo in Patients Receiving Ongoing Statin Therapy

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 and how ETC-1002 affects the levels of LDL-C (bad cholesterol) in patients receiving ongoing statin therapy.

Detailed Description
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Approximately 132 hypercholesterolemic patients already taking statin therapy to treat elevated LDL-C will be randomized in a ratio of 1:1:1 to receive either ETC-1002 (120 mg or 180 mg dose), or placebo for 12 weeks in addition to ongoing statin therapy. This study will explore the safety and efficacy of ETC-1002 when given to patients receiving statin therapy.

Official Title
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A Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of ETC-1002 Versus Placebo in Patients With Hypercholesterolemia Receiving Ongoing Statin Therapy

Conditions
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Hypercholesterolemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fasting, calculated mean LDL-C ≥130 mg/dL and ≤220 mg/dL Fasting mean TG level ≤400 mg/dL Stable statin therapy for at least 3 months prior to screening: atorvastatin (10 or 20 mg daily), simvastatin (5, 10 or 20 mg daily), rosuvastatin (5 or 10 mg daily), or pravastatin (10, 20 or 40 mg daily) Exclusion Criteria: Clinically significant cardiovascular disease within 12 months of screening Current muscle-related symptoms that may be due to ongoing statin therapy or a history of certain lab abnormalities that occurred during statin therapy and resolved when statin therapy was discontinued Type 1 diabetes or uncontrolled type 2 diabetes Use of metformin or thiazolidinediones (TZD) within 4 weeks of screening History of chronic musculoskeletal symptoms such as fibromyalgia Uncontrolled hypothyroidism Liver disease or dysfunction Renal dysfunction or nephritic syndrome Gastrointestinal conditions or procedures or surgeries Hematologic or coagulation disorders or low hemoglobin levels HIV or AIDS History of malignancy History of drug or alcohol abuse within 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>* ETC-1002 capsules, taken once daily oral<br>Drug: Statin Therapy<br>* Patients remained on ongoing statin therapy (not study provided) of either Atorvastatin 10mg or 20mg; Simvastatin 5mg, 10mg or 20mg; Rosuvastatin 5mg or 10mg; or Pravastatin 10mg, 20mg or 40mg.<br>|
| Experimental: ETC-1002 180 mg/day<br>Orally, once daily in morning as capsules | Drug: ETC-1002<br>* ETC-1002 capsules, taken once daily oral<br>Drug: Statin Therapy<br>* Patients remained on ongoing statin therapy (not study provided) of either Atorvastatin 10mg or 20mg; Simvastatin 5mg, 10mg or 20mg; Rosuvastatin 5mg or 10mg; or Pravastatin 10mg, 20mg or 40mg.<br>|
| Placebo Comparator: Placebo<br>Orally, once daily in morning | Drug: Placebo<br>* Placebo capsules, taken once daily oral<br>Drug: Statin Therapy<br>* Patients remained on ongoing statin therapy (not study provided) of either Atorvastatin 10mg or 20mg; Simvastatin 5mg, 10mg or 20mg; Rosuvastatin 5mg or 10mg; or Pravastatin 10mg, 20mg or 40mg.<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) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in non-high-density lipoprotein cholesterol (non-HDL-C) |  | 12 weeks | 
| Percent change in apolipoprotein B (ApoB) |  | 12 weeks | 
| Percent change in total cholesterol (TC) |  | 12 weeks | 
| Percent change in high-sensitivity C-reactive protein (hsCRP) |  | 12 weeks | 
| Percent change in triglycerides (TG) |  | 12 weeks | 
| Percent change in lipoprotein particle number |  | 12 weeks | 
| Safety using adverse event reports; clinical laboratory results |  | 12 weeks | 
| Safety using adverse event reports; vital signs |  | 12 weeks | 
| Pharmacokinetic plasma trough concentrations of ETC-1002 and metabolite 15228 |  | 12 weeks | 

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