A Study of Evacetrapib in High-Risk Vascular Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of the ACCELERATE study is to evaluate the efficacy and safety of evacetrapib in participants with high-risk vascular disease (HRVD).

Official Title
-----------------
Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High-Risk for Vascular Outcomes

Conditions
-----------------
Cardiovascular Diseases

Intervention / Treatment
-----------------
* Drug: Evacetrapib
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of high risk vascular disease (HRVD) (that is, meet at least one of the disease diagnostic criteria of: 1)History of acute coronary syndrome (ACS) (that is, ≥30 days through 365 days after discharge for ACS) 2)cerebrovascular atherosclerotic disease 3)peripheral arterial disease 4)diabetes mellitus with documented coronary artery disease and are clinically stable (as judged by the responsible physician). Must be treated with a statin for at least 30 days prior to screening. If not treated with a statin must have documented statin intolerance, or contraindication to statin Have a screening high-density lipoprotein cholesterol (HDL-C) ≤80 milligram per deciliter (mg/dL) (≤2.1 millimole per liter [mmol/L]) Have screening triglycerides (TG) ≤400 mg/dL (≤4.5 mmol/L) Meet 1 of the following criteria: screening low-density lipoprotein cholesterol (LDL-C) no more than 10 mg/dL (0.3 mmol/L) above the target chosen by the investigator (either LDL-C <100 mg/dL [<2.6 mmol/L] or LDL-C <70 mg/dL [<1.8 mmol/L]), OR if LDL-C is greater than target, the participant must be on maximum tolerated statin dose (for at least 30 days), have documented statin intolerance, or contraindication to statin Exclusion Criteria: Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Have previously completed or withdrawn from this study, or withdrawn from any other study investigating evacetrapib Female participants who are known to be pregnant or breastfeeding Women of child-bearing potential only, who test positive for pregnancy between screening and randomization, or who do not agree to use a reliable method of birth control during the study History of transient ischemic attack (TIA) or ischemic stroke <30 days and ACS <30 days Any reading of systolic blood pressure ≥180 millimeter of mercury (mm Hg) or diastolic blood pressure ≥110 mm Hg at screening or randomization History of hemorrhagic stroke or intracranial hemorrhage New York Heart Association class III or IV congestive heart failure Serum creatinine >2.2 mg/dL (>194.5 micromole per liter [μmol/L]) at screening Clinically active liver disease. Participants are not excluded due to Gilbert's Syndrome or a history of cholelithiasis/cholecystectomy History of malignancy within the preceding 3 years prior to screening Known malabsorption syndrome with the exception of lactose intolerance Participants with a known history of primary or secondary hyperaldosteronism Participants with a history of intolerance/hypersensitivity to cholesterol ester transfer protein (CETP) inhibitors Any clinically significant medical condition that according to the investigator could interfere with participation in the study Participants whose life expectancy is anticipated to be less than 4 years Unable or unwilling to comply with study requirements, or deemed by the investigator to be unfit for the study Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator Concurrent or anticipated need for treatment with niacin >250 mg/day or for chronic administration of drugs on the exclusion list Previous exposure to the CETP inhibitors dalcetrapib or evacetrapib within the last 3 months or anacetrapib within the last 12 months Any planned coronary angiography or coronary revascularization procedure. If angiography or revascularization is planned, participants may be screened and enrolled after all such planned procedures are completed.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evacetrapib<br>Evacetrapib 130 mg tablet, administered orally once daily for up to 4 years. Participants will also receive standard of care for high-risk vascular disease (HRVD). | Drug: Evacetrapib<br>* Administered Orally<br>* Other names: LY2484595;|
| Placebo Comparator: Placebo<br>Placebo, tablet administered orally once daily for up to 4 years. Participants will also receive standard of care for HRVD. | Drug: Placebo<br>* Administered Orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA) | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. | Baseline to Study Completion (Up to 4 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels |  | Baseline, 3 Months | 
| Number of Participants With Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. | Baseline through End of Study (Up to 4 years) | 
| Number of Participants With Composite Endpoint of CV Death, MI, or Coronary Revascularization | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. | Baseline through End of Study (Up to 4 years) | 
| Number of Participants With Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. | Baseline through End of Study (Up to 4 years) | 
| Number of Participants With Triple Composite Endpoint of CV Death, MI, or Stroke | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. | Baseline through End of Study (Up to 4 years) |