Clinical trial NCT00751231: A Phase 2 Safety and Efficacy Study of PRT060128, a Novel Intravenous and Oral P2Y12 Inhibitor, in Non-Urgent PCI
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Percutaneous Coronary Intervention
Keywords: PCI
percutaneous coronary intervention
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-09-11
Enrollment: 652
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 24 Hours/Discharge and Day 60
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Portola Investigational Site
state: California
city: Torrance
country: United States
facility: Portola Investigational Site
state: California
city: Washington
country: United States
facility: Portola Investigational Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Portola Investigational Site
state: Florida
city: Tallahassee
country: United States
facility: Portola Investigational Site
state: Florida
city: Augusta
country: United States
facility: Portola Investigational Site
state: Georgia
city: Lexington
country: United States
facility: Portola Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: Portola Investigational Site
state: Louisiana
city: Portland
country: United States
facility: Portola Investigational Site
state: Maine
city: Baltimore
country: United States
facility: Portola Investigational Site
state: Maryland
city: Detroit
country: United States
facility: Portola Investigational Site
state: Michigan
city: Grand Blanc
country: United States
facility: Portola Investigational Site
state: Michigan
city: Brooklyn
country: United States
facility: Portola Investigational Site
state: New York
city: Charleston
country: United States
facility: Portola Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Portola Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Portola Investigational Site
state: Ohio
city: Hershey
country: United States
facility: Portola Investigational Site
state: Pennsylvania
city: Lancaster
country: United States
facility: Portola Investigational Site
state: Pennsylvania
city: Seattle
country: United States
facility: Portola Investigational Site
state: Washington
city: Graz
country: Austria
facility: Portola Investigational Site
city: Vienna
country: Austria
facility: Portola Investigational Site
city: Calgary
country: Canada
facility: Portola Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: Portola Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: Portola Investigational Site
state: British Columbia
city: St. John's
country: Canada
facility: Portola Investigational Site
state: Newfoundland and Labrador
city: Newmarket
country: Canada
facility: Portola Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Portola Investigational Site
state: Ontario
city: Bad Oeynhausen
country: Germany
facility: Portola Investigational Site
city: Bad Rothenfelde
country: Germany
facility: Portola Investigational Site
city: Berlin
country: Germany
facility: Portola Investigational Site
city: Bernau
country: Germany
facility: Portola Investigational Site
city: Dachau
country: Germany
facility: Portola Investigational Site
city: Dortmund
country: Germany
facility: Portola Investigational Site
city: Dresden
country: Germany
facility: Portola Investigational Site
city: Göttingen
country: Germany
facility: Portola Investigational Site
city: Halle
country: Germany
facility: Portola Investigational Site
city: Hannover
country: Germany
facility: Portola Investigational Site
city: Heidelberg
country: Germany
facility: Portola Investigational Site
city: Kassel
country: Germany
facility: Portola Investigational Site
city: Kiel
country: Germany
facility: Portola Investigational Site
city: Langen
country: Germany
facility: Portola Investigational Site
city: Ludwigshafen
country: Germany
facility: Portola Investigational Site
city: Lübeck
country: Germany
facility: Portola Investigational Site
city: Mainz
country: Germany
facility: Portola Investigational Site
city: Munich
country: Germany
facility: Portola Investigational Site
city: Mönchengladbach
country: Germany
facility: Portola Investigational Site
city: Neuss
country: Germany
facility: Portola Investigational Site
city: Rostock
country: Germany
facility: Portola Investigational Site
city: Schwalmstadt
country: Germany
facility: Portola Investigational Site
city: Traunstein
country: Germany
facility: Portola Investigational Site
city: Trier
country: Germany
facility: Portola Investigational Site
city: Witten
country: Germany
facility: Portola Investigational Site
city: Wuppertal
country: Germany
facility: Portola Investigational Site
city: Bydgoszcz
country: Poland
facility: Portola Investigational Site
city: Gdansk
country: Poland
facility: Portola Investigational Site
city: Lodz
country: Poland
facility: Portola Investigational Site
city: Lublin
country: Poland
facility: Portola Investigational Site
city: Szczecin
country: Poland
facility: Portola Investigational Site
city: Warsaw
country: Poland
facility: Portola Investigational Site
Study officials:
affiliation: Duke University
name: Robert Harrington, MD
role: STUDY_CHAIR
affiliation: Duke University
name: Sunil V Rao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Robert C Welsh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.