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

Purpose

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.

Condition	Intervention	Phase
Non-Urgent PCI	Drug: clopidogrel Drug: PRT060128	Phase II

ChemIDplus related topics:

Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	A Randomized, Double-Blind, Active-Controlled Trial to Evaluate Intravenous and Oral PRT060128, a Selective and Reversible P2Y12 Inhibitor, vs Clopidogrel, as a Novel Antiplatelet Therapy in Patients Undergoing Non-Urgent PCI

Further study details as provided by Portola Pharmaceuticals:

Primary Outcome Measures:

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 [ Time Frame: 24 Hours/Discharge and Day 60 ] [ Designated as safety issue: No ]

Estimated Enrollment:	800
Study Start Date:	October 2008
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm 1: Active Comparator 300mg or 600mg loading dose of Clopidogrel followed by once daily dosing of 75 mg Clopidogrel for 60 days.	Drug: clopidogrel Loading dose of 300mg or 600mg, followed by once daily dosing of 75 mg
Arm 2: Experimental IV bolus of PRT060128 prior to PCI and twice daily administration of 50 mg oral PRT060128 for 60 days, with the first oral dose administered concurrently with the IV bolus.	Drug: PRT060128 80 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg
Arm 3: Experimental IV bolus of PRT060128 prior to PCI and twice daily administration of 100 mg oral PRT060128 for 60 days, with the first oral dose administered concurrently with the IV bolus.	Drug: PRT060128 80 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg
Arm 4: Experimental IV bolus of PRT060128 prior to PCI and twice daily administration of 150 mg oral PRT060128 for 60 days, with the first oral dose administered concurrently with the IV bolus.	Drug: PRT060128 80 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg

Detailed Description:

Each patient randomized in this trial will participate for approximately 12 weeks, including a Screening period of up to 2 weeks, the acute peri-procedural phase, and a 60-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, and a telephone follow-up 7 days following the last dose of study drug.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751231

Contacts


Contact: Gayle Paynter, RN BS MBA/MHA	919-668-8641	Gayle.e.paynter@duke.edu

Contact: Rita Weber	919-668-8173	Weber001@mc.duke.edu

Sponsors and Collaborators

Portola Pharmaceuticals

Investigators


Study Chair:	Robert Harrington, MD	Duke University

Principal Investigator:	Sunil V Rao, MD	Duke University

Principal Investigator:	Robert C Welsh, MD	University of Alberta

More Information

Responsible Party:	Portola Pharmaceuticals, Inc. ( Daniel Gretler, MD )
Study ID Numbers:	07-116
First Received:	September 10, 2008
Last Updated:	September 10, 2008
ClinicalTrials.gov Identifier:	NCT00751231
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada; Austria: Agency for Health and Food Safety; Germany: Federal Institute for Drugs and Medical Devices; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Portola Pharmaceuticals:

PCI

percutaneous coronary intervention

Study placed in the following topic categories:

Clopidogrel

Additional relevant MeSH terms:

Therapeutic Uses

Hematologic Agents

Platelet Aggregation Inhibitors

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 06, 2008

Sponsored by:	Portola Pharmaceuticals
Information provided by:	Portola Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00751231