A Clinical Outcomes Study of Darapladib versus Placebo in Subjects Following Acute Coronary Syndrome to Compare the Incidence of Major Adverse Cardiovascular Events (MACE).

Summary

This study is a randomized, placebo-controlled, double-blind, parallel group, multicenter,
event-driven trial. Subjects with ACS and receiving standard of care will be randomized
1:1 to once daily doses of Darapladib Enteric Coated Tablets, 160 mg or placebo. The
duration of the study will be determined by the rate of first occurrence of events that comprise the primary MACE composite. The study will be terminated when
approximately 1500 reports of first occurrence of MACE (primary endpoint) have
occurred. Based on current assumptions, it is anticipated that most subjects will be dosed
for a minimum of 2 years (except for those who permanently discontinue investigational
product or die) and up to 4.1 years or more. Median treatment duration is anticipated to
be approximately 3 years.
It is projected that the study will screen approximately 14,500 subjects with ACS in order
to randomize a minimum of approximately 11,500 total subjects, or at least 5750 subjects
per treatment arm. It is planned that subject accrual will occur across a minimum of
approximately 900 sites worldwide over a minimum period of approximately 24 months.
All subjects are to be followed until the termination of the study, regardless of whether
they permanently discontinue treatment with investigational product (IP) or experience a
non-fatal MACE. Ideally, subjects will continue treatment with IP after experiencing a
MACE

Participant Eligibility

1. Signed written informed consent prior to beginning study-related procedures (subject must understand the aims, investigational procedures and possible consequences of the study).
2. Male or female aged at least 18 years, inclusive, at randomization. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator and in accordance with local practice in relation to adequate contraception.In Taiwan,
subjects must be aged at least 20 years, inclusive, at randomization.
3. Hospitalization for ACS (unstable angina, non-ST segment elevation MI, or ST segment elevation MI) ≤30 days prior to randomization:
a. Unstable angina (UA) is defined as ischemic chest discomfort (or equivalent)
that occurs at rest with at least 1 episode lasting ≥10 minutes and is accompanied
by new or presumably new ST segment deviation (transient [<20 minutes]
elevation ≥0.1mV or dynamic horizontal/down-sloping depression ≥0.05mV) in at
least 2 contiguous leads without diagnostic biochemical changes in cardiac
enzymes (serum troponin I or T, or creatine kinase-MB).
b. Non-ST segment elevation MI (NSTEMI) is defined as ischemic chest
discomfort (or equivalent) that occurs at rest with at least 1 episode lasting ≥10
minutes and is accompanied by a diagnostic elevation in cardiac biomarkers of
myocardial injury (serum troponin I or T, or creatine kinase-MB ) above the upper
limit of normal without persistent ST segment elevation.
c. ST segment elevation MI (STEMI) is defined as prolonged symptoms of
ischemic chest discomfort (or equivalent) at rest (with at least 1 episode lasting
>20 min) and new or presumably new electrocardiographic changes (persistent ST
segment elevation ≥0.1 mV in ≥2 contiguous precordial leads or ≥2 adjacent limb
leads or new LBBB) that are accompanied by a diagnostic elevation in cardiac
biomarkers (serum troponin I or T, creatine kinase or creatine kinase-MB) above
the upper limit of normal.
4. All subjects must also have at least one of the following additional predictors of cardiovascular risk:
a. age ≥60 years at randomization.
b. history of documented MI prior to qualifying ACS event.
c. diabetes mellitus requiring pharmacotherapy.
d. significant renal dysfunction (defined as estimated glomerular filtration rate
[ eGFR] ≥30 and ≤59 mL/min per 1.73 m2).5,6
e.polyvascular disease manifested in this ACS population as coexistent clinically
diagnosed arterial disease in at least 1 peripheral arterial territory, defined as:
• cerebrovascular disease defined as carotid artery disease, or as prior ischemic
stroke that occurred >3 months prior to randomization [see definition(s)
below].
OR
• peripheral arterial disease (PAD)
in at least 2 arterial territories, defined as:
• cerebrovascular disease defined as carotid artery disease,or as prior ischemic
stroke that occurred >3 months prior to randomization [see definition(s)
below].
OR
• peripheral arterial disease (PAD)
5. The subject must be clinically stable for 24 hours prior to randomization (clinical stability is defined as the absence of chest pain, hemodynamic instability [e.g., hypotension, requirement for inotropic therapy], or significant arrhythmia [e.g., arrhythmia requiring treatment]).
6. For subjects in whom a PCI is planned as part of management for the qualifying ACS event, the subjects should undergo PCI prior to randomization whenever possible.