Study to find out whether “Evacetrapib” can help patients who suffer from blockages in the blood vessels to their heart, brain, or legs who are at high risk for having a heart attack, stroke or may even die from the disease

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2012-000061-21-LT
• Date of registration: 28/09/2012
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: Study to find out whether “Evacetrapib” can help patients who suffer from blockages in the blood vessels to their heart, brain, or legs who are at high risk for having a heart attack, stroke or may even die from the disease
• Scientific title: 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 - ACCELERATE
• Date of first enrolment: 04/12/2012
• Target sample size: 12000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000061-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, Estonia, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Democratic People's Republic of, Lithuania, Mexico, Netherlands, New Zealand, Peru, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Eli Lilly

• Name: Clinical Trial Information
• Affiliation: Eli Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
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:
1. ST-segment elevation =1 mm in 2 or more contiguous ECG leads
2. New or presumably new left bundle branch block (LBBB)
3. 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 th
Exclusion 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 µmol/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 m

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

High Risk Vascular Disease (HRVD)
MedDRA version: 16.1 Level: LLT Classification code 10067825 Term: Peripheral arterial disease System Organ Class: 100000004866
MedDRA version: 16.1 Level: PT Classification code 10051592 Term: Acute coronary syndrome System Organ Class: 10007541 - Cardiac disorders
MedDRA version: 16.1 Level: PT Classification code 10011078 Term: Coronary artery disease System Organ Class: 10007541 - Cardiac disorders
MedDRA version: 16.1 Level: LLT Classification code 10003602 Term: Atherosclerosis cerebral System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Evacetrapib
Product Code: LY2484595
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: -
CAS Number: 1186486-62-3
Current Sponsor code: LY2484595
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 130-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Time to first occurrence of any component of the composite cardiovascular (CV) events of death, myocardial infarction (MI), stroke, coronary revascularization, or hospitalization for unstable angina (UA).

Main Objective: The primary objective of this study is to test the hypothesis that evacetrapib 130 mg daily, in comparison to placebo, reduces the incidence of the composite endpoint of cardiovascular (CV) death, mycocardial infarction (MI), storke, coronary revascularization, or hospitalization for unstable angina (UA) in high-risk vascular disease (HRVD) patients.

Secondary Objective: The secondary objectives of the study are to test the hypotheses that evacetrapib 130 mg daily, in HRVD patients compared to placebo:
• Increases high-density lipoprotein-cholesterol (HDL-C) at 3 months after randomization
• Decreases low-density lipoprotein-cholesterol (LDL-C) at 3 months after randomization
Reduces the incidence of the following:
• A composite endpoint of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for UA
• Composite endpoint of CV death, MI, or coronary revascularization
• Composite endpoint of CV death, MI, stroke, or hospitalization for UA
• Composite endpoint of CV death, MI, or stroke
• Recurrence of any component of the primary composite endpoint among those who had already reached the primary endpoint
• Coronary revascularization
• MI
• CV death
• All-cause mortality
• Hospitalization for UA
• Stroke

Timepoint(s) of evaluation of this end point: Until all of the following criteria are satisfied: 1) at least 1400 patients experience 1 or more components of the primary composite endpoint of CV death, MI, stroke, coronary revascularization, or hospitalization for UA; 2) at least 700 patients experience 1 or more components of the composite endpoint of CV death, MI, or stroke; 3) at least 1.5 years have elapsed from the date of last patient randomized

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: HDL-C and LDL-C are evaluated at 3 months after randomization.

The other Secondary endpoints are event driven

Secondary end point(s): Compared to placebo:
-Percent change from baseline of mean HDL-C levels at 3 months after randomization
-Percent change from baseline of mean LDL-C levels at 3 months after randomization
Time to first occurrence of:
-A composite endpoint of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for UA
-Composite endpoint of CV death, MI, or coronary revascularization
- Composite endpoint of CV death, MI, stroke, or hospitalization for UA
- Composite endpoint of CV death, MI, or stroke
Time to first recurrence of:
- Any component of the primary composite endpoint among those who had already reached the primary endpoint
Time to first occurrence of:
-Coronary revascularization
-MI
Time to:
-CV death
- All-cause mortality
Time to first occurrence of:
- Hospitalization for UA
- Stroke

Secondary ID(s)

I1V-MC-EIAN

2012-000061-21-GB

Source(s) of Monetary Support

Eli Lilly and Company