Safety and Tolerability of E5555 and Its Effects on Markers of Intravascular Inflammation in Subjects With Coronary Artery Disease

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of E5555, and Its Effects on Markers of Intravascular Inflammation in Subjects With Coronary Artery Disease

The primary purpose of this study is to assess the safety and tolerability of E5555 in subjects with coronary artery disease.

This was a multicenter, randomized, double-blind, placebo-controlled trial of E5555, a PAR-1 inhibitor. The total duration of individual study participation was 28 weeks (196 days). This included a treatment period of 24 weeks (168 days) and a follow-up period of 4 weeks (28 days).

INCLUSION CRITERIA:

1. Males or Females, 45 - 80 years of age

2. Confirmed coronary artery disease defined as one of the following:

   • Post-acute coronary syndrome or myocardial infarction or
   • Post percutaneous coronary intervention or coronary artery bypass graft or oAngina pectoris with documented (electrocardiogram or imaging study) ischemia or
   • Angiographically documented lesion occluding ≥70% of a coronary vessel

   And at high risk as defined as one or more of the following:

   • Elevated hsCRP (high-sensitivity C-reactive protein)
   • Diabetes mellitus
   • History of carotid artery disease and/or peripheral artery disease
   • Thrombo-embolic transient ischemic attack or stroke >1 year prior to screening

3. All subjects must be receiving low dose aspirin and/or clopidogrel and/or ticlopidine.

EXCLUSION CRITERIA

1. History of acquired or congenital bleeding disorder, coagulopathy or platelet disorder, or history of pathological bleeding within the last 6 months
2. History of intracranial bleeding, history of hemorrhagic retinopathy or known structural cerebral vascular lesion
3. Clinically significant hematological, hepatic or renal abnormalities
4. Patients with some specific ST-segment changes, severe congestive heart failure or uncontrolled cardiac arrhythmias at baseline
5. Recent significant (as determined by the investigator) cardiovascular events