A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol

Study Overview
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Brief Summary
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The purpose of the ACCENTUATE study is to evaluate whether the study drug known as evacetrapib is effective in treating participants with high cholesterol and atherosclerotic cardiovascular disease (ASCVD) and/or diabetes.

Official Title
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The Addition of Evacetrapib to Atorvastatin Compared to Placebo, High Intensity Atorvastatin, and Atorvastatin With Ezetimibe to Evaluate LDL-C Lowering in Patients With Primary Hyperlipidemia - The ACCENTUATE Study

Conditions
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Hyperlipidemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be treated with atorvastatin 40 mg/day for at least 30 days prior to screening Have an LDL-C >70 mg/deciliter(dL) or non-HDL-C >100 mg/dL Have screening triglycerides ≤400 mg/dL (≤4.5 millimoles/Liter) Individuals with ASCVD and/or individuals with type 1 or type 2 diabetes Exclusion Criteria: Have a hemoglobin A1c (HbA1c) >9.5% New York Heart Association (NYHA) class III or IV congestive heart failure History of either a transient ischemic stroke or ischemic stroke <30 days History of acute coronary syndrome (ACS) <30 days

Ages Eligible for Study
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Minimum Age: 18 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: Atorvastatin + Evacetrapib<br>Atorvastatin 40 milligrams (mg) orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. | Drug: Evacetrapib<br>* Administered orally<br>* Other names: LY2484595;Drug: Atorvastatin<br>* Administered orally<br>Drug: Placebo<br>* Administered orally<br>|
| Active Comparator: Atorvastatin 80 mg<br>Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. | Drug: Atorvastatin<br>* Administered orally<br>Drug: Placebo<br>* Administered orally<br>|
| Active Comparator: Atorvastatin + Ezetimibe<br>Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. | Drug: Atorvastatin<br>* Administered orally<br>Drug: Ezetimibe<br>* Administered orally<br>Drug: Placebo<br>* Administered orally<br>|
| Active Comparator: Atorvastatin 40 mg<br>Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. | 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 3 Months in Low-Density Lipoprotein Cholesterol (LDL-C) | Change in LDL-C levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. LDL-C was measured by beta quantification. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. Least Square Means (LS means) and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable. | Baseline, 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to 3 Months in High-Density Lipoprotein Cholesterol (HDL-C) | Change in HDL-C levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. LS medians and median differences were analyzed in log units and converted to standard units. Statistics are from mixed model repeated measures analysis with log baseline measurement, treatment, visit, and treatment by visit interaction included in the model. Log percent change from baseline response is the dependent variable. Within-participant repeated measures at multiple visits are modeled by a compound symmetry covariance structure. | Baseline, 3 Months | 
| Percent Change From Baseline to 3 Months in Apolipoprotein AI (apoAI) | Change in apoAI levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable. | Baseline, 3 Months | 
| Percent Change From Baseline to 3 Months in Non-HDL-C | Change in Non-HDL-C levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. LS medians and median differences were analyzed in log units and converted to standard units. Statistics are from mixed model repeated measures analysis with log baseline measurement, treatment, visit, and treatment by visit interaction included in the model. Log percent change from baseline response is the dependent variable. Within-participant repeated measures at multiple visits are modeled by a compound symmetry covariance structure. | Baseline, 3 Months | 
| Percent Change From Baseline to 3 Months in Apolipoprotein B (apoB) | Change in apoB levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable. | Baseline, 3 Months | 
| Percent Change From Baseline to 3 Months in Cholesterol Efflux Capacity | Change in cholesterol efflux capacity from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable. | Baseline, 3 Months | 
| Percent Change From Baseline to 3 Months in Lipoprotein(a) (Lp[a]) | Change in Lp(a) levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable. | Baseline, 3 Months |