| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Reduction of atherothrombotic events in patients with acute coronary syndromes (ACS) that is patients with ST-segment elevation MI [STEMI], non-ST-segment elevation MI [NSTEMI], or unstable angina [UA], who are to undergo percutaneous coronary intervention (PCI). | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 | | E.1.2 | Level | HLT | | E.1.2 | Classification code | 10011085 | |
| 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 primary objective of this study is to test the hypothesis that CS-747 plus aspirin is superior to clopidogrel plus aspirin in the treatment of subjects with acute coronary syndrome who are to undergo percutaneous coronary intervention, as measured by a reduction in the composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke at a median follow-up of at least 12 months.
CS-747 will be given as an oral loading dose of 60 mg, followed by an oral maintenance dose of 10 mg once daily (QD). Clopidogrel will be given as an oral loading dose of 300 mg, followed by an oral maintenance dose of 75 mg QD.
The primary endpoint will be analyzed first in the subjects with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI), followed by analysis of the same endpoint in all ACS subjects (UA, NSTEMI and ST-segment elevation myocardial infarction [STEMI]). | |
| E.2.2 | Secondary objectives of the trial | To compare CS-747 with clopidogrel with respect to the risk of:
· CV death, MI or UTVR at 30 and 90 days.
· CV death, MI or stroke at 30 and 90 days.
· CV death, MI, stroke or rehospitalization for cardiac ischemic events at a median of at least 12 months.
· All-cause death, MI or stroke at a median of at least 12 months.
These endpoints will be analyzed in both the UA/NSTEMI population and the entire ACS population
The safety objectives for this study are to evaluate the:
· Incidence of non-CABG-related TIMI major bleeding.
· Incidence of life-threatening bleeding.
· Incidence of non-CABG-related TIMI minor bleeding.
· Overall safety and tolerability of CS-747 based on clinical findings, laboratory values and the occurrence of TEAEs. | |
| 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 | *Protocol Sample Banking, 2004-09-30, H4T-MC-TAAL4. To collect one additional blood sample (ca20ml) per patient to be stored for future DNA analyses. Samples will be anonymised to protect patient privacy.
* STEMI-substudy - An Assessment of Angiographic and Static ECG Measures of Reperfusion, 2005-03-24, H7T-MC-TAAL5. To assess whether or not treatment with prasugrel as compared with clopidogrel is associated with improvement in STRES following PCI, to assess whether or not treatment with prasugrel as compared with clopidogrel is associated with improved myocardial perfusion following primary PCI.
* Pharmacokinetic Substudy of Two Inactive Metabolites, 2005-04-04, H7T-MC-TAAL7 To assess the population pharmacokinetics of prasugrel metabolites in subjects who are to undergo PCI.
*Unstable Angina/Non-STEMI Subjects Treated with Aspirin and a Glycoprotein IIb/IIIa Antagonist, 2005- 05-11, H7T-MC-TAAL11. To assess if prasugrel plus aspirin and GP IIb/IIIa antagonist results in a decrease in the composite endpoint at 30 days, 180 days, and median follow-up of 1 year compared with clopidogrel plus aspirin and a GP IIb/IIIa antagonist.
| |
| E.3 | Principal inclusion criteria | Subjects are eligible to be included in the study only if they meet all of the following
criteria:
[1] Present with acute coronary syndrome based on the disease
diagnostic criteria and are to undergo percutaneous coronary
intervention (PCI).
[2] Are of a legal age (and at least 18 years of age) and competent mental
condition to provide written informed consent before entering the
study. Informed consent must be signed by the study participant or
authorized representative, according to local rules and regulations.
[3] For women of child-bearing potential only (that is, women who are not
surgically or chemically sterilized and who are between menarche and
1 year postmenopause), test negative for pregnancy between ACS
presentation and enrollment (based on a urine or serum pregnancy test)
and agree to use a reliable method of birth control during the study.
| |
| E.4 | Principal exclusion criteria | Subjects will be excluded from the study if they meet any of the following criteria:
Cardiovascular Exclusion Criteria
[4] Have cardiogenic shock
[5] Have refractory ventricular arrhythmias.
[6] Have NYHA Class IV congestive heart failure
Bleeding Risk Exclusion Criteria
[7] Have received fibrin-specific fibrinolytic therapy <24 hours prior to randomization.
[8] Have received nonfibrin-specific fibrinolytic therapy <48 hours prior to randomization.
[9] Have active internal bleeding or history of bleeding diathesis.
[10] Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding.
[11] 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.
[12] Have an INR known to be >1.5 at the time of evaluation.
[13] Have a platelet count of <100,000/mm3 at the time of screening.
[14] Have anemia (hemoglobin <10 g/dL) at the time of screening.
Prior/Concomitant Therapy Exclusion Criteria
[15] Have received one or more doses of a thienopyridine =<5 days prior to PCI.
[16] Are receiving or will receive oral anticoagulation or other antiplatelet therapy that cannot be safely discontinued for the duration of the study.
[17] Are receiving daily treatment with NSAIDs or 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
[21] Have previously completed or withdrawn from this study or any other
study investigating CS-747.
[22] Are women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding.
[23] Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator is associated with reduced survival over the expected treatment period (maximum of 15 months).
[24] Have known severe hepatic dysfunction (i.e. cirrhosis or portal hypertension).
[25] Have a condition associated with poor treatment compliance, including alcoholism, mental illness, or drug dependence.
[26] Have a history of intolerance or allergy to aspirin or approved thienopyridines (ticlopidine or clopidogrel). | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary endpoint is the composite of CV death, nonfatal MI, or nonfatal stroke. Due to a potentially varying hazard ratio, the primary analysis will be the time from randomization to the onset of the first occurrence of the primary endpoint using the Gehan-Wilcoxon test. Primary analyses will be carried out in a hierarchical manner. At the first step, distribution of time-to-first occurrence of the primary endpoint will be compared using a two-sided significance level of 0.05 in UA/NSTEMI. Conditional on successfully establishing superiority of the CS-747 treatment in UA/NSTEMI, distribution of time-to-first occurrence of the primary endpoint will be compared using a two-sided significance level of 0.05 in all ACS (UA/NSTEMI/STEMI) subjects. In this analysis, UA/NSTEMI and STEMI classification will be used as a stratification factor. | |
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description | |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | |
| 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 | | Last visit of the last subject. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
