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: 11 April 2016
• Main ID: EUCTR2012-000061-21-IT
• Date of registration: 19/10/2012
• 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: 19/12/2012
• Target sample size: 11000
• 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, Germany, Hungary, India, Israel, Italy, Japan, Korea, Democratic People's Republic of, Lithuania, Mexico, Netherlands, New Zealand, Peru, Poland, Puerto Rico, Russian Federation, Slovakia, South Africa, Spain, Sweden, 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 forACS)2)Cerebrovascular Atherosclerotic Disease3)Peripheral Arterial Disease 4)Diabetes Mellitus with Documented Coronary Artery Disease.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. For further details please refer to the Study Protocol.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3850

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 <30days 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 months or anacetrapib within the last 12

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

Health Condition(s) or Problem(s) studied

High Risk Vascular Disease (HRVD)
MedDRA version: 14.1 Level: SOC Classification code 10047065 Term: Vascular disorders System Organ Class: 10047065 - Vascular disorders
MedDRA version: 14.1 Level: PT Classification code 10051592 Term: Acute coronary syndrome System Organ Class: 10007541 - Cardiac disorders
MedDRA version: 14.1 Level: PT Classification code 10011078 Term: Coronary artery disease System Organ Class: 10007541 - Cardiac disorders
MedDRA version: 14.1 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
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)

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

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.

Timepoint(s) of evaluation of this end point: Until all of the following criteria are satisfied: 1) at least 1136 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 500 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)

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, coronaryrevascularization, 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

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 ID(s)

2012-000061-21-GB

I1V-MC-EIAN

Source(s) of Monetary Support

Eli Lilly and Company