A Clinical Trial to Demonstrate the Efficacy of Cangrelor

Official Title: “A Clinical Trial Comparing Cangrelor to Clopidogrel in Subjects Who Require Percutaneous Coronary Intervention.”

The primary objective of this study is to demonstrate that the efficacy of cangrelor is superior, or at least non-inferior, to that of clopidogrel in subjects requiring PCI.

Two (2) separate sub-studies will be conducted at selected study sites: - TMC-CAN-05-02-S1 "The effect of cangrelor on the pharmacodynamics of clopidogrel" to determine whether the administration of a cangrelor infusion prior to administration of a 600 mg loading dose of clopidogrel has any effect on the extent of platelet inhibition by clopidogrel - TMC-CAN-05-02-S2 "A cangrelor population pharmacokinetics modeling study" to develop a population pharmacokinetic (PK) model for cangrelor from data obtained from ongoing Phase III studies of patients with coronary atherosclerosis requiring percutaneous coronary intervention (PCI)

Intervention(s) in this Clinical Trial

• Drug: cangrelor (P2Y12 inhibitor)
  • Bolus (30 ug/kg) & infusion (4 ug/kg/min) administered within 30 minutes of the start of PCI - infusion to continue minimum of 2 hours and no longer than 4 hours.
• Drug: clopidogrel (P2Y12 inhibitor)
  • 600 mg active clopidogrel given 30 minutes prior to the start of PCI.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • placebo capsules (to match) + cangrelor bolus -(30 ug/kg) & infusion (4ug/kg/min)
• Active Comparator: 2
  • clopidrogrel capsules (600 mg) + placebo bolus & infusion (to match)

Primary Measures

• All-cause mortality, MI, and IDR
  • Time Frame: 48 hours
    Safety Issue?: No

Secondary Measures

• Death, IDR
  • Time Frame: 30 days
    Safety Issue?: No

INCLUSION CRITERIA

To be included in this study, subjects must meet the following criteria:

• Angiography demonstrating atherosclerosis amenable to treatment by PCI with or without stent implantation and diagnosis of Acute Coronary Syndrome by elevated cardiac markers or ischemic chest discomfort w/electrocardiogram changes + age > 65 or diabetes or ST-elevation MI.

EXCLUSION CRITERIA

Subjects will be excluded from the study if they present with any of the following:

• 1. Not a candidate for PCI
• 2. Increased bleeding risk: ischemic stroke within the last year or any previous hemorrhagic stroke, tumor, cerebral arteriovenous malformation, or intracranial aneurysm; recent (<1 month) trauma or major surgery (including by-pass surgery);
• currently receiving warfarin, active bleeding
• 3. Impaired hemostasis: known International Normalized Ratio (INR) >1.5 at screening;
• past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count
• <100,000/µL), or history of thrombocytopenia or neutropenia associated with clopidogrel
• 4. Severe hypertension not adequately controlled by antihypertensive therapy at the time of randomization
• 5. Receipt of fibrinolytic therapy in the 12 hours preceding randomization
• 6. Receipt of clopidogrel dose exceeding maintenance dose (ie, >75 mg) at any time in the 5 days preceding randomization
• 7. Inability to swallow study capsules
• 8. Glycoprotein IIb/IIIa (GPI) Inhibitor usage within the previous 12 hours (applicable to UA and NSTEMI patients)
• Subjects excluded for any of the above reasons may be re-screened for participation at any time if the exclusion characteristic has changed.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: The Medicines Company Industry

Overall Clinical Trial Officials and Contacts

Deepak L. Bhatt, MD Principal Investigator The Cleveland Clinic  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00305162

Study ID Number: TMC-CAN-05-02

ClinicalTrials.gov Identifier: NCT00305162

Health Authority: United States: Food and Drug Administration