A Study of Evacetrapib (LY2484595) in Japanese Participants With Primary Hypercholesterolemia

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of the study drug known as evacetrapib in Japanese participants with primary hypercholesterolemia. The double blind treatment period will last for 12 weeks and the open-label extension period will last for an additional 40 weeks.

Official Title
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A Double-Blind Efficacy and Safety Study of Evacetrapib Followed by an Open-Label Extension in Japanese Patients With Primary Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Evacetrapib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese outpatients who are diagnosed with primary hypercholesterolemia with LDL-C levels (measured by a direct method at baseline) that meet the following criteria. (Participant categories are based on the definition in Japan Atherosclerosis Society 2012 guidelines.) Category I: 160 mg/deciliter (dL)≤LDL-C<200 mg/dL Category II: 140 mg/dL≤LDL-C<175 mg/dL Category III: 120 mg/dL≤LDL-C<150 mg/dL Have triglycerides (TG) ≤400 mg/dL. Have HDL-C <100 mg/dL. Exclusion Criteria: Participants on LDL apheresis or plasma apheresis. Participants with secondary hypercholesterolemia or familial hypercholesterolemia. Any planned angiography. If angiography is planned, participants may be screened and enrolled after all such planned procedures are completed. History of any of the following any conditions: Stable angina or acute coronary syndrome (unstable angina, myocardial infarction), old myocardial infarction or a coronary revascularization procedure including stent placement, or symptomatic carotid artery disease peripheral arterial disease ischemic stroke or transient ischemic attack (TIA) intracranial hemorrhage abdominal aortic aneurysm Have systolic blood pressure (SBP) >160 millimeters of mercury (mm Hg) or diastolic blood pressure (DBP) >100 mm Hg. Have a hemoglobin A1c ≥8.4% (National Glycohemoglobin Standardization Program). During the study period, participants who plan to use, are likely to require, or unwilling or unable to stop with adequate washout any prescription, over the counter medication, supplements or health foods with the intent to treat serum lipids (LDL-C, HDL-C, TG) including but not limited to these classes of drugs: statin, ezetimibe, bile acid sequestrant, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Participants taking probucol, fibrate or nicotinic agents within 8 weeks before screening are excluded from the study. Have been exposed to cholesteryl ester transfer protein inhibitors (e.g., anacetrapib or dalcetrapib).

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evacetrapib<br>130 milligrams (mg) evacetrapib given orally (PO) once a day for 12 weeks. Participants begin open label extension (130 mg evacetrapib given orally once a day for 40 weeks) after week 12. | Drug: Evacetrapib<br>* Administered orally<br>* Other names: LY2484595;|
| Placebo Comparator: Placebo<br>Placebo given PO once a day for 12 weeks. Participants begin open label extension (130 mg evacetrapib given PO once a day for 40 weeks) after week 12. | Drug: Evacetrapib<br>* Administered orally<br>* Other names: LY2484595;Drug: Placebo<br>* Administered orally<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 Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification | Least Square Mean (LS mean) using mixed model repeated measures (MMRM) adjusted for baseline, treatment, visit , and treatment*visit, where the participant is a random effect. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) | LS mean using MMRM adjusted for baseline, treatment, visit , and treatment*visit, where the participant is a random effect. | Baseline, Week 12 | 
| Percent Change From Baseline in LDL-C (Direct) | LS mean using MMRM adjusted for baseline, treatment, visit , and treatment*visit, where the participant is a random effect. | Baseline, Week 12 | 
| Percent Change From Baseline in Non HDL-C | LS mean using MMRM adjusted for baseline, treatment, visit , and treatment*visit, where the participant is a random effect. | Baseline, Week 12 | 
| Percent Change From Baseline in Lipoprotein-a | LS Mean from analysis of covariance (ANCOVA) model adjusted for baseline and treatment. | Baseline, Week 12, Week 52 | 
| Percent Change From Baseline in Apolipoprotein A-I | LS Mean from ANCOVA model adjusted for baseline and treatment. | Baseline, Week 12, Week 52 | 
| Percent Change From Baseline in Apolipoprotein B | LS Mean from ANCOVA model adjusted for baseline and treatment. | Baseline, Week 12, Week 52 |