A Phase 2 Safety and Efficacy Study of PRT060128, a Novel Intravenous and Oral P2Y12 Inhibitor, in Non-Urgent PCI

Phase 2

Completed

Conditions: Percutaneous Coronary Intervention

Interventions: Drug: clopidogrel
Drug: PRT060128

Registration Number: NCT00751231

Lead Sponsor: Portola Pharmaceuticals

Brief Summary: This is a multi-center, randomized, double-blind, triple-dummy, clopidogrel-controlled study of IV and oral PRT060128 compared to clopidogrel in patients undergoing non-urgent (including elective) PCI. After diagnostic angiography, patients scheduled for non-urgent PCI will be randomized to clopidogrel or to one of three dose levels of PRT060128.

Detailed Description: Each patient randomized in this trial will participate for approximately 12-24 weeks, including a Screening period of up to 2 weeks, the acute peri-procedural phase, and a 60-120 day chronic treatment phase. The chronic phase includes daily in-hospital assessments until 24 Hours or Discharge (whichever comes first), a telephone follow-up on Day 7-10 post-Discharge, outpatient follow-up visits on Days 30 and 60-67, \[Day 90 and Day 120 (if treated for 120 days)\] and a telephone follow-up 7 days following the last dose of study drug.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 652

Inclusion Criteria

The patient is scheduled to undergo non-urgent PCI
The patient is between 18 and 75 years of age (inclusive) and willing to comply with the protocol
Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of dosing. All patients must agree to use double barrier contraception during the study and for at least 4 weeks after their last dose.
The patient or legally acceptable representative is able to read and give written informed consent and has signed an informed consent form approved by the Investigator's IRB/IEC

Exclusion Criteria

Estimated or measured weight < 55 kg
Acute non-ST-segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) within 7 days prior to PCI
Chronic total occlusion or unprotected left main stenting
Cardiogenic shock (systolic blood pressure < 90 mm Hg requiring vasopressor or hemodynamic support)
Uncontrolled hypertension at the time of initial study drug administration defined as measured systolic blood pressure > 190 mm Hg or diastolic blood pressure > 108 mm Hg
Planned staged PCI
Planned surgery during the study period
Planned GP IIb/IIIa use
Patient has received a clopidogrel loading dose (≥300 mg) within 7 days prior to randomization; patients on maintenance clopidogrel may be enrolled
The planned administration of the study-specified clopidogrel loading dose is >12 hours prior to PCI
Administration of thrombolytic agents, fondaparinux, or oral anticoagulants (e.g., warfarin) within the 7 days prior to PCI
Estimated creatinine clearance (e.g. Cockcroft-Gault) < 45 mL/min
Anemia with hemoglobin level < 10 g/dL
Thrombocytopenia (platelet count < 100,000/mm3)
ALT and/or AST > 2.5 x the ULN or other indication of clinically significant hepatic dysfunction
Facial or head trauma within the last 30 days
Intraocular hemorrhage within the last 30 days
Gastrointestinal bleeding within the last 30 days
Active bleeding, or history of a bleeding disorder or known intracranial vascular malformation
History of any prior ischemic stroke or TIA within the last 5 years or intracranial hemorrhage, neoplasm, or arteriovenous malformation
Known allergy or contraindication to the components of PRT060128, aspirin, heparin, clopidogrel, glycoprotein IIb/IIIa inhibitors, or to any contrast media
Participation in any investigational drug study within 30 days prior to enrollment. Participation in a device trial prior to enrollment is acceptable
Prior participation in any study involving PRT060128
Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the patient's risk by participating in the study. This would include, but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy or any unexplained blackouts

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	clopidogrel	300mg or 600mg loading dose of Clopidogrel followed by once daily dosing of 75 mg Clopidogrel for up to 120 days.
Arm 3	PRT060128	IV bolus of PRT060128 prior to PCI and twice daily administration of 100 mg oral PRT060128 for up to 120 days, with the first oral dose administered concurrently with the IV bolus.
Arm 2	PRT060128	IV bolus of PRT060128 prior to PCI and twice daily administration of 50 mg oral PRT060128 for up to 120 days, with the first oral dose administered concurrently with the IV bolus.
Arm 4	PRT060128	IV bolus of PRT060128 prior to PCI and twice daily administration of 150 mg oral PRT060128 for up to 120 days, with the first oral dose administered concurrently with the IV bolus.

Primary Outcome Measures

Name	Time	Method
The study is not powered to examine a pre-specified endpoint; rather it is designed to explore a number of analyses to understand the clinical efficacy, biological activity, and tolerability and safety of PRT060128 in patients undergoing non-urgent PCI	24 Hours/Discharge and Day 60

Secondary Outcome Measures