E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adjunctive antiplatelet prior, during and after non-urgent percutaneous coronary intervention (PCI) in patients with coronary artery disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065608 |
E.1.2 | Term | Percutaneous coronary intervention |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011078 |
E.1.2 | Term | Coronary artery disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective f the trial is to evaluate how dose relates to the clinical efficacy, safety, and tolerability of IV and oral PRT060128 in patients undergoing non-urgent PCI. Specific objectives include characterizing the incidence and type of bleeding events during both the acute and chronic phases, and evaluating the biological activity and efficacy of PRT060128 versus clopidogrel. The study is not powered to examine a pre-specified endpoint. Rather, the intent is to examine a number of endpoints in order to develop sufficient understanding of clinical efficacy, biological activity, tolerability, and safety of PRT060128 in non-urgent PCI patients |
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E.2.2 | Secondary objectives of the trial |
An additional objective is to obtain population PK data in the study population. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
07-116A: Platelet Function Sub Study for INNOVATE - PCI (07-116): Objectives: - To determine the PK and PD effects of PRT060128 administered as an IV bolus followed by chronic oral dosing compared to clopidogrel administered orally as 300-600 mg loading dose followed by chronic dosing in patients undergoing non-urgent PCI - To determine the PD effects of oral PRT060128 as compared to clopidogrel on Day 30 in the target population - To determine the PK/PD relationship for PRT060128 in the target patient population. |
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E.3 | Principal inclusion criteria |
1. The patient is scheduled to undergo non-urgent PCI 2. The patient is between 18 and 75 years of age (inclusive) and willing to comply with the protocol 3. Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of dosing. All patients must agree to use two forms of contraception during the study and for at least 4 weeks after their last dose. One of the methods must consist of oral or onjected contraceptives, transdermal hormone patch, subdermal implants, IUD with hormones or copper, or surgical sterilization. 4. 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 |
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E.4 | Principal exclusion criteria |
1. Estimated or measured weight < 55 kg 2. Acute non-ST-segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) within 7 days prior to PCI 3. Chronic total occlusion or unprotected left main stenting 4. Cardiogenic shock (systolic blood pressure < 90 mm Hg requiring vasopressor or hemodynamic support) 5. Uncontrolled hypertension at the time of initial study drug administration defined as measured systolic blood pressure (SBP) > 190 mm Hg or diastolic blood pressure (DBP) > 108 mm Hg 6. Planned staged PCI 7. Planned surgery during the study period 8. Planned GP IIb/IIIa use 9. Patient has received a clopidogrel loading dose (≥300 mg) within 7 days prior to randomization; patients on maintenance clopidogrel may be enrolled 10. The planned administration of the study-specified clopidogrel loading dose is >12 hours prior to PCI 11. Administration of thrombolytic agents, fondaparinux, or oral anticoagulants (e.g., warfarin) within the 7 days prior to PCI or requirement for chronic oral antocoagulation 12. Estimated creatinine clearance (e.g., Cockcroft-Gault) < 45 mL/min 13. Anemia with hemoglobin level < 10 g/dL 14. Thrombocytopenia (platelet count < 100,000/mm3) 15. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 x the upper limit of normal (ULN) or other indication of clinically significant hepatic dysfunction 16. Facial or head trauma within the last 30 days 17. Intraocular hemorrhage within the last 30 days 18. Gastrointestinal bleeding within the last 30 days. 19. Active bleeding, or history of a bleeding disorder or known intracranial vascular malformation 20. History of any prior ischemic stroke or TIA within the last 5 years or intracranial hemorrhage, neoplasm, or arteriovenous malformation 21. Known allergy or contraindication to the components of PRT060128, aspirin, heparin, clopidogrel, glycoprotein IIb/IIIa inhibitors, or to any contrast media 22. Participation in any investigational drug study within 30 days prior to enrollment. Participation in a device trial prior to enrollment is acceptable 23. Prior participation in any study involving PRT060128 24. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints Clinical Efficacy Endpoints 1. Composite of death, MI, stroke, and urgent target vessel revascularization (UTVR) within 24 hours or Discharge (whichever occurs first) 2. Composite of death, MI, stroke, UTVR, and stent thrombosis within 24 hours or Discharge (whichever occurs first) 3. Composite of death, MI, stroke, UTVR, and GP IIb/IIIa thrombotic bailout within 24 hours or Discharge (whichever occurs first) 4. Composite of death, MI, stroke, UTVR, stent thrombosis, and GP IIb/IIIa thrombotic bailout within 24 hours or Discharge (whichever occurs first) 5. Composite of death, MI, stroke, and UTVR by Day 60 6. Composite of death, MI, stroke, UTVR and stent thrombosis by Day 60 7. Composite of death, MI, stroke, and UTVR by day 120 8. Composite of death, MI, stroke, UTVR and stent thrombosis by Day 120 9. All individual components of endpoints 1-8 (death, MI, stroke, UTVR, stent thrombosis, and GP IIb/IIIa thrombotic bailout) Biological Efficacy Endpoints 10. Any troponin elevation by 24 hours or discharge (whichever occurs first) 11. Any troponin elevation > 2x the upper limit of normal by 24 hours or discharge (whichever occurs first) 12. Peak troponin within 24 hours or discharge (whichever occurs first) Safety/Tolerability Endpoints: 1. The occurence of clinically Relevant (Major or Minor) or Nuisance Bleeding within 24 hours or Discharge (whichever occurs first) 2. The occurence of clinically Relevant (Major or Minor) or Nuisance Bleeding by Day 60 3. The occurence of clinically Relevant (Major or Minor) or Nuisance Bleeding by Day 120 4. The occurence of TIMI Bleeding (Major, Minor or Bleeding Requiring Medical Attention) within 24 hours or Discharge (whichever occurs first) 5. The occurence of TIMI Bleeding (Major, Minor or Bleeding Requiring Medical Attention) by Day 60 6. The occurence of TIMI Bleeding (Major, Minor or Bleeding Requiring Medical Attention) by Day 120 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the trial will be the last visit of the last subject. Each subject's last visit will be a follow up visit 120 to 127 days after enrollment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |