Protocol I1V-MC-EIAN Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High-Risk for Vascular Outcomes - the ACCELERATE Study

Patients with HRVD are defined by at least 1 of the following 4 groups. Note that an eligible patient may meet inclusion criteria for more than 1 group.;1) History of ACS (that is, *30 days through 365 days after discharge for ACS)
For the purposes of this study, ACS will include 1) unstable angina and non-ST-segment elevation myocardial infarction [UA/NSTEMI] and 2) ST-segment elevation myocardial infarction [STEMI] as follows:
* UA is defined as a history of chest discomfort or ischemic symptoms of *10 minutes duration at rest with persistent or transient ST-segment deviation *1 mm in 1 or more electrocardiogram (ECG) leads without elevation of creatine kinase-myocardial bands (CK-MB) or troponin T or I.
* NSTEMI is defined as a history of chest discomfort or ischemic symptoms of *10 minutes duration at rest with no evidence of persistent ST-segment elevation. Patients must also have CK-MB or troponin T or I greater than the 99th percentile upper reference limit or the upper limit of normal (ULN). If CK-MB or troponin is not available, total CK greater than 99th percentile upper reference limit (or ULN) is acceptable.
* STEMI is defined as a history of chest discomfort or ischemic symptoms of >20 minutes duration at rest with 1 of the following present on at least 1 electrocardiogram (ECG) prior to randomization:
a. ST-segment elevation *1 mm in 2 or more contiguous ECG leads
b. New or presumably new left bundle branch block (LBBB)
c. ST-segment depression *1 mm in 2 anterior precordial leads with clinical history and evidence suggestive of true posterior infarction;Patients will have either undergone successful coronary revascularization associated with the ACS event prior to date of anticipated randomization or are not anticipated to undergo coronary revascularization.
Patients will NOT qualify for the trial on the basis of MI related to revascularization intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) performed outside the setting of an acute ACS.;2) Cerebrovascular Atherosclerotic Disease
* History of transient ischemic attack (TIA) or ischemic stroke (*30 days) with carotid stenosis *50% in the distribution of the clinical event, or
* Asymptomatic carotid artery stenosis *70%, or
* A history of carotid artery revascularization;3) Peripheral Arterial Disease
Peripheral arterial disease (PAD) for this study will be defined as current intermittent claudication or resting limb ischemia and either an ankle-brachial index (ABI) *0.90, or a history of atherosclerotic limb ischemia leading to previous noncoronary revascularization or amputation.
Patients will NOT qualify for the trial on the basis of isolated renal artery stenosis in the absence of other inclusion criteria.;4) Diabetes Mellitus with Documented Coronary Artery Disease
Diabetes mellitus (DM) patients are defined as either receiving concomitant treatment with an oral or parenteral hypoglycemic agent and/or insulin, or being managed by diet alone, as a result of a preexisting diagnosis of DM. A new diagnosis is based on plasma glucose measurements or glycated hemoglobin (HbA1c) levels (with anticipated treatment with an oral or parenteral hypoglycemic agent and/or insulin, or to be managed by diet alone). Patients with DM must have CAD documented by a previous MI, PCI, CABG, or >50% angiographic stenosis of *1 major coronary artery.;Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] Males or females *18 years of age with a diagnosis of HRVD (that is, meet at least 1 of the disease diagnostic criteria described above), and are clinically stable (as judged by the responsible physician)
[2] Must be treated with a statin for at least 30 days prior to screening. If not treated with a statin, patients must have documented statin intolerance, or contraindication to statin (as defined in the protocol)
[3] Have a screening HDL-C *80 mg/dL (*2.1 mmol/L)
[4] Have screening triglycerides (TG) *400 mg/dL (*4.5 mmol/L)
[5] Meet 1 of the following criteria:
a) screening 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
b) if LDL-C is greater than target, the patient must be on maximum tolerated statin dose (for at least 30 days), have documented statin intolerance, or contraindication to statin
[6] At the time of screening, are able and willing to give written informed consent

Patients will be excluded from the study if they meet any of the following criteria:;General Exclusion Criteria:;[7] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted;[8] Are Lilly employees or are employees of the Academic Research Organization (ARO) or Clinical Research Organization (CRO) (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly employees may participate in Lilly-sponsored clinical studies but are not permitted to participate at a Lilly facility. Immediate family is defined above;[9] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study;[10] Have previously completed or withdrawn from this study, or withdrawn from any other study investigating evacetrapib;Medical Conditions Exclusion Criteria:;[11] Females who are known to be pregnant;[12] Females who are breastfeeding;[13] Women of child-bearing potential only (that is, women who are not surgically or chemically sterilized and who are between menarche and 1 year postmenopause), who test positive for pregnancy between screening and randomization (based on the required urine or serum pregnancy test) or who do not agree to use a reliable method of birth control during the study;[14] History of transient ischemic attack (TIA) or ischemic stroke <30 days and ACS <30 days;[15] Any reading of systolic blood pressure *180 mm Hg or diastolic blood pressure *110 mm Hg at screening or randomization;[16] History of hemorrhagic stroke or intracranial hemorrhage;[17] New York Heart Association class III or IV congestive heart failure;[18] Serum creatinine >2.2 mg/dL (>194.5 *mol/L) at screening;[19] Clinically active liver disease (for example, esophageal varices, jaundice, ascites, cholestasis, acute or chronic hepatitis). Patients are not excluded due to Gilbert*s Syndrome or a history of cholelythiasis/cholecystectomy;[20] History of malignancy (except for nonmelanoma skin cancer/basal cell or squamous cell carcinoma of the skin) within the preceding 3 years prior to screening;[21] Known malabsorption syndrome with the exception of lactose intolerance;[22] Patients with a known history of primary or secondary hyperaldosteronism;[23] Patients with a history of intolerance/hypersensitivity to cholesterol ester transfer protein (CETP) inhibitors;[24] Any clinically significant medical condition that according to the investigator could interfere with participation in the study;[25] Patients whose life expectancy is anticipated to be less than 4 years;[26] Unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study;[27] Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator;Prior/Concomitant Therapy Exclusion Criteria:;[28] Concurrent or anticipated need for treatment with niacin >250 mg/day ;[29] Concurrent or anticipated need for chronic administration of drugs on the exclusion list;[30] Previous exposure to (or participation in a trial of) the CETP inhibitors dalcetrapib or evacetrapib within the last 3 months or anacetrapib within the last 12 months.;Procedure Exclusion Criteria:;[31] Any planned coronary angiography or coronary revascularization procedure. If angiography or revascularization is planned, patients may be screened and enrolled after all such planned procedures are completed