E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
subjects undergoing elective cardiac catheterization with planned percutaneous coronary intervention (PCI) with coronary stenting. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023031 |
E.1.2 | Term | Ischemia coronary artery origin |
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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 |
-To compare the inhibition of platelet aggregation (IPA) to 20 µM adenosine diphosphate (ADP) measured at 6 hours (±30 minutes) after prasugrel 60 mg loading dose (LD) versus clopidogrel 600 mg LD in subjects in the “on treatment population” who did not receive a GPIIb/IIIa inhibitor. -To compare the IPA to 20 µM ADP measured after 14±2 days of prasugrel 10 mg daily maintenance dose (MD) versus the IPA after 14±2 days of clopidogrel 150 mg daily MD in the “on treatment population” who have received PCI (this includes subjects receiving clopidogrel and prasugrel in either order during the crossover phase). |
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E.2.2 | Secondary objectives of the trial |
- To compare the inhibition of platelet aggregation (IPA) after Prasugrel(P) 60 mg loading dose (LD) versus clopidogrel(C) 600 mg LD in subjects in the “on treatment population” who did not receive a GPIIb/IIIa inhibitor. - To compare overall safety and tolerability of P 60 mg LD and 10 mg daily MD versus C 600 mg LD and 150 mg daily MD after 14±2 days in treated subjects who have received PCI. - To compare overall safety and tolerability of the following dosing regimens: P 60 mg LD and 10 mg daily MD for 14±2 days with crossover to C 150 mg daily MD for 14±2 days versus C 600 mg LD and 150 mg daily MD for 14±2 days with crossover to P 10 mg daily MD for 14±2 days in treated subjects who have received PCI. - To compare P versus C in the occurrence of Major Adverse Cardiac Events (MACE) after 14±2 days in treated subjects who have received PCI. - To compare P versus C on additional measures of platelet inhibition. - To compare P versus C in measures of myonecrosis following PCI. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Subjects ≥18 years of age undergoing cardiac catheterization with planned percutaneous coronary intervention (if coronary anatomy is suitable) for an indication of chest pain +/or anginal equivalent felt by the treating physician to be related to coronary ischemia. [2] At least one of the following (a through c): a) Functional study (exercise, or pharmacologic) within the past 8 weeks consistent with ischemia as manifested by at least one of the following: 1. A reversible defect on nuclear imaging. 2. A reversible wall-motion abnormality by echocardiography. 3. Horizontal or down-sloping ST-depressions >1 mm on electrocardiogram (ECG) (if no imaging performed). b) Prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)]. c) A cardiac catheterization with at least one coronary artery lesion amenable to PCI (not yet performed) within 14 days prior to enrollment.
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E.4 | Principal exclusion criteria |
Cardiovascular Exclusion Criteria [1] Known creatine kinase-myocardial bands (CK-MB) or cardiac troponin greater than the upper limit of normal (ULN) at the time of screening. [2] Have a planned PCI procedure as initial treatment for an acute myocardial infarction (MI) (STEMI or NSTEMI), or a planned PCI within 48 hours of fibrinolytic therapy for STEMI. [3] Have cardiogenic shock at the time of screening (systolic blood pressure <90 mm Hg associated with clinical evidence of end-organ hypoperfusion, or subjects requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion). [4] Have refractory ventricular arrhythmias. [5] Have New York Heart Association (NYHA) Class IV congestive heart failure (CHF) (see Attachment 4 for NYHA CHF classifications). Bleeding Risk Exclusion Criteria [6] Have active internal bleeding or history of bleeding diathesis. [7] Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding. [8] Have any of the following: a) Prior history of hemorrhagic stroke. b) Intracranial neoplasm, arteriovenous malformation, or aneurysm. c) Ischemic stroke ≤3 months prior to screening. [9] Have an International Normalized Ratio (INR) known to be >1.5 at the time of screening. [10] Have a platelet count of <100,000/mm3 at the time of screening. [11] Have anemia (hemoglobin [Hgb] <10 gm/dL) at the time of screening. Prior/Concomitant Therapy Exclusion Criteria [12] Have received one or more doses of a thienopyridine (ticlopidine or clopidogrel) ≤5 days prior to PCI. [13] Have been administered a GPIIb/IIIa inhibitor within the past 7 days or plans to use a GPIIb/IIIa inhibitor during PCI. [14] Are receiving or will receive oral anticoagulation or oral antiplatelet therapy (other than aspirin) that cannot be safely discontinued for the duration of the study. [15] Are receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued or are anticipated to require >2 weeks of daily treatment with NSAID or COX2 inhibitors during the study. General Exclusion Criteria [16] Are investigative site personnel directly affiliated with the study or are immediate family of investigative site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [17] Are employed by Eli Lilly & Company, Ube Industries Limited, Daiichi Sankyo Company Limited, The TIMI Study Group, or the contract research organization (CRO) (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly employees may participate in Lilly sponsored clinical studies but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [18] Have received treatment within the last 30 days with a drug or device that has not received regulatory approval for any indication at the time of study entry or are presently enrolled in another drug or device study. [19] Have previously completed or withdrawn from this study or any other study investigating prasugrel. [20] Are women who are known to be pregnant, who have given birth within the past 90 days, who are breastfeeding, or of child-bearing potential who test negative for pregnancy at Period 1, but refuse to use a reliable method of birth control (that is, barrier, hormonal, or abstinence) during the study. [21] Have a concomitant medical illness (for example, terminal malignancy or severe hepatic dysfunction) that in the opinion of the investigator is associated with reduced survival over the expected treatment period (maximum of 35 days). [22] Have a condition associated with poor treatment compliance, including alcoholism, mental illness, or drug dependence. [23] Have a history of intolerance or allergy to aspirin or approved thienopyridines (ticlopidine or clopidogrel).
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E.5 End points |
E.5.1 | Primary end point(s) |
-Inhibition of platelet aggregation (IPA) to 20 µM adenosine diphosphate (ADP) by light transmission aggregometry (LTA) at 6 hours (±30 minutes) after loading dose of study drug. IPA is defined as (1- [maximal platelet aggregation at time x after drug treatment]/[maximal platelet aggregation before drug treatment]) × 100. -IPA to 20 µM ADP measured after 14±2 days of prasugrel 10 mg daily maintenance dose (MD) and the IPA after 14±2 days of clopidogrel 150 mg daily MD (this includes subjects receiving clopidogrel and prasugrel in either order during the crossover phase). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
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 | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |