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

NCT ID: NCT00751231

Last Updated: 2023-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 652 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2010-04-30

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.

Conditions

Percutaneous Coronary Intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1

300mg or 600mg loading dose of Clopidogrel followed by once daily dosing of 75 mg Clopidogrel for up to 120 days.

Group Type: ACTIVE_COMPARATOR

clopidogrel

Intervention Type: DRUG

Loading dose of 300mg or 600mg, followed by once daily dosing of 75 mg

Arm 2

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.

Group Type: EXPERIMENTAL

PRT060128

Intervention Type: DRUG

80-120 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg

Arm 3

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.

Group Type: EXPERIMENTAL

PRT060128

Intervention Type: DRUG

80-120 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg

Arm 4

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.

Group Type: EXPERIMENTAL

PRT060128

Intervention Type: DRUG

80-120 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg

Interventions

clopidogrel

Loading dose of 300mg or 600mg, followed by once daily dosing of 75 mg

Intervention Type: DRUG

PRT060128

80-120 mg IV bolus administered prior to PCI, followed by twice daily dosing of oral 50mg, 100mg or 150mg

Intervention Type: DRUG

Other Intervention Names

Plavix

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Portola Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Harrington, MD

Role: STUDY_CHAIR

Duke University

Sunil V Rao, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Robert C Welsh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

Portola Investigational Site

La Jolla, California, United States

Portola Investigational Site

Torrance, California, United States

Portola Investigational Site

Washington D.C., District of Columbia, United States

Portola Investigational Site

Jacksonville, Florida, United States

Portola Investigational Site

Tallahassee, Florida, United States

Portola Investigational Site

Augusta, Georgia, United States

Portola Investigational Site

Lexington, Kentucky, United States

Portola Investigational Site

New Orleans, Louisiana, United States

Portola Investigational Site

Portland, Maine, United States

Portola Investigational Site

Baltimore, Maryland, United States

Portola Investigational Site

Detroit, Michigan, United States

Portola Investigational Site

Grand Blanc, Michigan, United States

Portola Investigational Site

Brooklyn, New York, United States

Portola Investigational Site

Charleston, North Carolina, United States

Portola Investigational Site

Winston-Salem, North Carolina, United States

Portola Investigational Site

Cincinnati, Ohio, United States

Portola Investigational Site

Hershey, Pennsylvania, United States

Portola Investigational Site

Lancaster, Pennsylvania, United States

Portola Investigational Site

Seattle, Washington, United States

Portola Investigational Site

Graz, , Austria

Portola Investigational Site

Vienna, , Austria

Portola Investigational Site

Calgary, Alberta, Canada

Portola Investigational Site

Edmonton, Alberta, Canada

Portola Investigational Site

Vancouver, British Columbia, Canada

Portola Investigational Site

St. John's, Newfoundland and Labrador, Canada

Portola Investigational Site

Newmarket, Ontario, Canada

Portola Investigational Site

Toronto, Ontario, Canada

Portola Investigational Site

Bad Oeynhausen, , Germany

Portola Investigational Site

Bad Rothenfelde, , Germany

Portola Investigational Site

Berlin, , Germany

Portola Investigational Site

Bernau, , Germany

Portola Investigational Site

Dachau, , Germany

Portola Investigational Site

Dortmund, , Germany

Portola Investigational Site

Dresden, , Germany

Portola Investigational Site

Göttingen, , Germany

Portola Investigational Site

Halle, , Germany

Portola Investigational Site

Hanover, , Germany

Portola Investigational Site

Heidelberg, , Germany

Portola Investigational Site

Kassel, , Germany

Portola Investigational Site

Kiel, , Germany

Portola Investigational Site

Langen, , Germany

Portola Investigational Site

Ludwigshafen, , Germany

Portola Investigational Site

Lübeck, , Germany

Portola Investigational Site

Mainz, , Germany

Portola Investigational Site

Mönchengladbach, , Germany

Portola Investigational Site

Munich, , Germany

Portola Investigational Site

Neuss, , Germany

Portola Investigational Site

Rostock, , Germany

Portola Investigational Site

Schwalmstadt, , Germany

Portola Investigational Site

Traunstein, , Germany

Portola Investigational Site

Trier, , Germany

Portola Investigational Site

Witten, , Germany

Portola Investigational Site

Wuppertal, , Germany

Portola Investigational Site

Bydgoszcz, , Poland

Portola Investigational Site

Gdansk, , Poland

Portola Investigational Site

Lodz, , Poland

Portola Investigational Site

Lublin, , Poland

Portola Investigational Site

Szczecin, , Poland

Portola Investigational Site

Warsaw, , Poland

Countries

United States; Austria; Canada; Germany; Poland

References

Welsh RC, Rao SV, Zeymer U, Thompson VP, Huber K, Kochman J, McClure MW, Gretler DD, Bhatt DL, Gibson CM, Angiolillo DJ, Gurbel PA, Berdan LG, Paynter G, Leonardi S, Madan M, French WJ, Harrington RA; INNOVATE-PCI Investigators. A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial. Circ Cardiovasc Interv. 2012 Jun;5(3):336-46. doi: 10.1161/CIRCINTERVENTIONS.111.964197. Epub 2012 May 29.

Reference Type: DERIVED

PMID: 22647518 (View on PubMed)

Angiolillo DJ, Welsh RC, Trenk D, Neumann FJ, Conley PB, McClure MW, Stephens G, Kochman J, Jennings LK, Gurbel PA, Wojcik J, Dabrowski M, Saucedo JF, Stumpf J, Buerke M, Broderick S, Harrington RA, Rao SV. Pharmacokinetic and pharmacodynamic effects of elinogrel: results of the platelet function substudy from the intravenous and oral administration of elinogrel to evaluate tolerability and efficacy in nonurgent percutaneous coronary intervention patients (INNOVATE-PCI) trial. Circ Cardiovasc Interv. 2012 Jun;5(3):347-56. doi: 10.1161/CIRCINTERVENTIONS.111.965608. Epub 2012 May 22.

Reference Type: DERIVED

PMID: 22619259 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/22647518

A Randomized, Double-Blind, Active-Controlled Phase 2 Trial to Evaluate a Novel Selective and Reversible Intravenous and Oral P2Y12 Inhibitor Elinogrel Versus Clopidogrel in Patients Undergoing Nonurgent PCI: The INNOVATE-PCI Trial

http://www.ncbi.nlm.nih.gov/pubmed/22619259

Pharmacokinetic and Pharmacodynamic Effects of Elinogrel: Results of the Platelet Function Substudy From the Intravenous and Oral Administration of Elinogrel to Evaluate Tolerability and Efficacy in Nonurgent PCI Patients (INNOVATE-PCI) Trial

Other Identifiers

2008-001352-51

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

07-116

Identifier Type: -

Identifier Source: org_study_id