E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
subjects with acute coronary syndrome |
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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 | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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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 establish superiority of a prasugrel 10-mg daily maintenance dose compared with a clopidogrel 150-mg daily maintenance dose |
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E.2.2 | Secondary objectives of the trial |
*To assess and compare a prasugrel 10-mg daily maintenance dose(MD) with a clopidogrel 150-mg daily MD as assessed by: - mean MPA to 5 µM ADP at the end of two 14-day treatment periods in subjects with ACS - mean IPA to 5 and 20 µM ADP at the end of two 14-day treatment periods in subjects with ACS *To compare the pharmacodynamic effect, as assessed by the phosphorylation status of VASP expressed as the mean [PRI] *To assess and compare the levels of ADP-induced P2Y12 reaction units *To assess and compare the levels of ADP-induced MPA *To compare a prasugrel 10-mg daily MD with a clopidogrel 150-mg daily MD *To estimate the effect on platelet aggregation of changing from a clopidogrel 900-mg loading dose to the initial MD *To explore the safety and tolerability of the daily MD of prasugrel versus clopidogrel *To explore the safety of prasugrel MD initiated after a clopidogrel 900-mg loading dose
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Present with acute coronary syndrome (ACS) based on the disease diagnostic criteria and have planned treatment, as part of standard of care, with a one-time 900-mg loading dose of commercially available clopidogrel. [2] Are of a legal age (and at least 18 years of age to less than 85 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. |
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E.4 | Principal exclusion criteria |
Cardiovascular Exclusion Criteria [4] Have overt ST-segment elevation myocardial infarction (STEMI). [5] Have cardiogenic shock (systolic blood pressure <90 mmHg associated with clinical evidence of end-organ hypoperfusion, or subjects requiring vasopressors to maintain systolic blood pressure over 90 mmHg and associated with clinical evidence of end-organ hypoperfusion). [6] Have refractory ventricular arrhythmias. [7] Have New York Heart Association (NYHA) Class IV congestive heart failure (CHF; see Attachment TABN.3 for NYHA CHF classifications). [8] Have severe and uncontrolled hypertension. Bleeding Risk Exclusion Criteria [9] Have fibrin-specific fibrinolytic therapy planned within the 24-hour period prior to randomization. [10] Have nonfibrin-specific fibrinolytic therapy planned within the 48-hour period prior to randomization. [11] Have active internal bleeding or history of bleeding diathesis. [12] Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding. [13] 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 Visit 1. [14] Known International Normalized Ratio (INR) of >1.5. [15] Have a platelet count of <100,000/mm3. [16] Have anemia (hemoglobin [Hgb] <10 gm/dL). Prior/Concomitant Therapy Exclusion Criteria [17] Have received any GPIIb/IIIa inhibitors less than 30 days prior to study entry or anytime during the study. [18] Are receiving or will receive oral anticoagulation or other antiplatelet therapy (other than aspirin, low molecular weight heparin, or hirudin) that cannot be safely discontinued for the duration of the study. [19] Are currently receiving chemotherapy or radiation therapy. General Exclusion Criteria [20] Are investigator site personnel directly affiliated with the study or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [21] Are employed by Eli Lilly & Company, Daiichi Sankyo, Inc., 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. [22] Have received treatment within the last 30 days with a drug 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. [23] Have previously completed or withdrawn from this study or any other study investigating prasugrel. [24] 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 Visit 1 , but refuse to use a reliable method of birth control (that is barrier, hormonal, or abstinence) during the study. [25] Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator is associated with reduced survival over the next 15 months. [26] Have any other condition, chronic illness, or medication that, in the opinion of the investigator, would preclude participation in the study. [27] Have known severe hepatic dysfunction (that is, with cirrhosis or portal hypertension). [28] Have low neutrophil count (<1,200/mm3). [29] Have a condition associated with poor treatment compliance, including alcoholism, mental illness, or drug dependence. [30] Have a history of intolerance or allergy to aspirin or approved thienopyridines (ticlopidine or clopidogrel). [31] May be unable to cooperate with protocol requirements and follow-up procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
platelet aggregation response to adenosine diphosphate (ADP) |
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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 | No |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
900mg LD of Clopidogrel is independant of the trial.If given, patient is eligible to enter the trial |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |