A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin 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 when administered in combination with atorvastatin for 12 weeks in Japanese participants with primary hypercholesterolemia.

Official Title
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A Double-Blind Efficacy and Safety Study of Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Evacetrapib
* Drug: Ezetimibe
* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be treated with atorvastatin 10 mg/day for at least 30 days prior to study initiation. Japanese outpatients who are diagnosed with primary hypercholesterolemia with LDL-C levels (measured by a direct method) 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 Category II: 140 mg/dL≤LDL-C Category III: 120 mg/dL≤LDL-C Secondary prevention: 100 mg/dL≤LDL-C 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 homozygous 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 conditions < 90 days prior to study initiation acute coronary syndrome (unstable angina, acute myocardial infarction) symptomatic peripheral arterial disease invasive treatment of carotid artery disease ischemic stroke or transient ischemic attack (TIA) intracranial hemorrhage History of abdominal aortic aneurysm. Participants with a history of intolerance/hypersensitivity to ezetimibe or statins. 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 (OTC) 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 (except for atorvastatin 10 mg), ezetimibe, bile acid sequestrant, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Participants taking probucol, fibrate or nicotinic agents within 8 weeks before study initiation are excluded from the study. Have been exposed to cholesteryl ester transfer protein (CETP) inhibitors (for example, 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 and 10 mg atorvastatin administered PO once a day for 12 weeks. | Drug: Evacetrapib<br>* Administered orally<br>* Other names: LY2484595;Drug: Atorvastatin<br>* Administered orally<br>|
| Active Comparator: Ezetimibe<br>10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm. | Drug: Ezetimibe<br>* Administered orally<br>Drug: Atorvastatin<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks. | Drug: Atorvastatin<br>* Administered orally<br>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 | The mixed-effects model for repeated measures (MMRM) was used for the Least Squares Mean (LS Mean) estimates at Week 12 for LDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, Visit (4,5,6, or 7), and treatment-by-visit interaction as fixed effects, and participant as a random effect. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol (HDL-C) | The MMRM was used for the LS Mean estimates at Week 12 for HDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect, and treatment-by-visit interaction as fixed effects, and participant as a random effect. | Baseline, Week 12 | 
| Percent Change From Baseline to Week 12 in LDL-C (Direct) | The MMRM was used for the LS Mean estimates at Week 12 for LDL-C (direct) adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect. | Baseline, Week 12 | 
| Percent Change From Baseline to Week 12 in Non HDL-C | The MMRM was used for the LS Mean estimates at Week 12 for Non HDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect. | Baseline, Week 12 | 
| Percent Change From Baseline to Week 12 in Lipoprotein-a | The analysis of covariance (ANCOVA) model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline. | Baseline, Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein A-I | The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline. | Baseline, Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B | The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline. | Baseline, Week 12 |