E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The primary objective of the study is to compare the platelet inhibition of ticagrelor versus clopidogrel in post-MI patients in terms of platelet reactivity at the end of the 2 study periods (pre-crossover and post crossover). |
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E.1.1.1 | Medical condition in easily understood language |
patients with prior myocardial infarction |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10007541 |
E.1.2 | Term | Cardiac disorders |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007649 |
E.1.2 | Term | Cardiovascular disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 primary objective of the study is to compare the platelet inhibition of ticagrelor versus clopidogrel in post-MI patients in terms of platelet reactivity at the end of the 2 study periods (pre-crossover and post crossover). |
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E.2.2 | Secondary objectives of the trial |
To compare the platelet inhibition of ticagrelor versus clopidogrel in terms of VerifyNow P2Y12 assay % inhibition, using the TRAP-induced (BASE channel) response and High platelet reactivity rate (PRU >208) at the end of the 2 study periods (pre-crossover and post crossover). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Provision of informed consent prior to any study specific procedures 2.Post-menopausal female (defined as absence of any vaginal bleeding for a year) or male aged >50 years 3.A spontaneous MI (ST or Non ST segment elevation) 1 to 3 years before enrolment. In addition, at least one of the following high-risk features: age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous MI, multivessel coronary artery disease, or non-end stage renal disease (estimated creatinine clearance of <60 ml per minute). 4.For male participants, receipt of agreement on using effective contraceptive method throughout the duration of their participation in the study (condom ) .
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E.4 | Principal exclusion criteria |
1.Planned use of a P2Y12 receptor antagonist, dipyridamole, cilostazol, or anticoagulant therapy during the study period; 2.Known allergy, intolerance, hypersensitivity to ticagrelor or clopidogrel or any excipients, 3.Active pathological bleeding, severe hepatic impairment, a bleeding disorder or a history of an ischemic stroke or intracranial bleeding, a central nervous system tumor, or an intracranial vascular abnormality; 4.Gastrointestinal bleeding within the previous 6 months or major surgery within the previous 30 days; 5.Concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inhibitors (atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole, grapefruit juice over 1 litre daily), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or inducers (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, and rifapentine).
6.Increased risk of bradycardic events (e.g. known sick sinus syndrome or third degree AV block or previous documented syncope suspected to be due to bradycardia unless treated with a pacemaker). 7.Inability to adhere to the follow-up requirements or any other reason or condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.
The following restrictions should also be applied to the subjects participating in this study:
1. Male subjects should be willing to use barrier methods of contraception during the study and for time period equal to 5 half-lives of the assigned investigational agent after end of study, unless their partners are post-menopausal, surgically sterile or are using accepted contraceptive methods. 2. Subjects should not receive treatment during the study with any of the disallowed medications outlined in the Exclusion Criteria (Section 4.2; Exclusion Criteria).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will undergo platelet reactivity assessment with the VerifyNow assay in PRU at visit 2, 3 and 4. |
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E.5.2 | Secondary end point(s) |
•High platelet reactivity rate (defined as >208 PRU) at the end of the 2 study periods •VerifyNow P2Y12 assay % inhibition, using the TRAP-induced (BASE channel) response at the end of the 2 study periods •The number and proportion of subjects experience any adverse event. •The total number of bleeding events [defined by the Bleeding Academic Research Consortium (BARC) criteria] and the incidence rate of bleeding for ticagrelor compared to clopidogrel throughout the study.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between Visit 2 of the First Patient enrolled till the end of the trial ( 32 days after Visit 2 of the Last Patient enrolled in the study) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
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
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LVLS (Last Visit Last Subject) |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |