| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| The investigation will be carried out on subjects with Acute Coronary Syndromes. |
|
| MedDRA Classification |
| 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 evaluate the safety and tolerability of different doses and dose regimens of YM150 on top of standard treatment with Acetyl Salicylic Acid (ASA) with or without clopidogrel in the secondary prevention of Ischemic Vascular Events in Subjects with recent ACS |
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| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• To evaluate the efficacy of different doses and dose regimens of YM150 on top of standard treatment with ASA with or without clopidogrel in the secondary prevention of Ischemic Vascular Events in Subjects with recent ACS,
• To compare safety, tolerability and efficacy of different doses and dose regimens of YM150 on top of standard treatment with ASA with or without clopidogrel against placebo.
Other Objectives:
• To assess Pharmacokinetic and Pharmacodynamic (PKPD) properties in the target population,
• To further define the suitable subject population for further development (i.e. P III).
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion criteria are: male or female subject who:
1. has a diagnosis of STE-ACS, NSTE-ACS as index event according to accepted guidelines such as the ESC or AHA guideline,
2. has elevated cardiac biomarkers (cardiac Troponin T or I or CKMB) 2x ULN for CK-MB or > ULN for troponin,
3. has at least one of the following additional high risk factors for ischemic events:
• New ST-T deviations on Electrocardiogram (ECG)
• Age of 65 years or older
• Previous ACS < 12 months prior to randomization
• Multi vessel Coronary Artery Disease (CAD)
• Ischemic stroke or Transient Ischemic Attack (TIA) >12 months prior to randomization
• Type 2 Diabetes Mellitus
• Peripheral Arterial Disease (PAD),
4. is clinically stable which is defined as discontinuation of parenteral antithrombotics and is not likely to require reinstallment of parenteral antithrombotics at time of randomization and receives current standard oral antiplatelet therapy,
5. is able to be randomized within 7 days after presentation with STE-ACS or NSTE-ACS following management to current best clinical practice in the study centre. This may include thrombolysis or primary Percutaneous Coronary intervention (PCI) for STE-ACS, or early invasive strategy (including PCI) for non-STE-ACS subjects. Subjects should be randomized as soon as possible after discontinuation of parenteral antithrombotics,
6. has provided Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations or Informed Consent has been obtained from the legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable),
7. is 18 years of age (legal minimum age required per country) or older at time of informed consent.
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|
| E.4 | Principal exclusion criteria |
Exclusion criteria at time of randomization: subject
1. requires ongoing parenteral or oral anticoagulant therapy (such as vitamin K antagonists, Unfractionated Heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, thrombin inhibitors), thrombolytics (such as Tissue Plasminogen Activator (TPA), streptokinase), Glycoprotein (GP) IIb/IIIa antagonists or other antiplatelet drugs (such as cilostazol, ticlopidine, dipyridamole, prasugrel),
2. is planned for myocardial revascularization (e.g., Coronary Artery Bypass Graft (CABG) or elective or staged PCI) or any other invasive procedure with increased risk for bleeding (i.e. elective surgical procedures) within 60 days after randomization,
3. has active bleeding or is in the opinion of the investigator at high risk of bleeding during the study,
4. has had recent stroke or TIA ≤ 12 months prior to index event,
5. has a bleeding diathesis or any other condition or laboratory abnormality with an increased tendency for bleeding (e.g., platelet count below 100.000/uL),
6. is a female of childbearing potential who refuses to use a medically acceptable form of contraception throughout the study. Acceptable methods of contraception include the following: oral or injectable hormonal contraceptives, intrauterine devices, vaginal hormonal rings, and only in combination with a male condom, a vaginal diaphragm or cervical caps. Male study subjects should be advised to use male condom in addition to having their partner use another acceptable method during the study and for three months after the last dose,
7. is a female who is pregnant or lactating or has a positive pregnancy test within 72 hours prior to randomization;
8. has persistent blood pressure of 160 mmHg systolic or higher and/or 100 mmHg diastolic or higher at baseline with or without medication,
9. has hepatic insufficiency or presents with ALT > 2.0 times the ULN or total bilirubin > 1.5 times the ULN (result based on (local) laboratory testing on blood sample drawn within maximally 24 hours prior to randomization),
10. has a estimated renal creatinine clearance of <60 mL/min as calculated by the Cockcroft-Gault equation (result based on (local) laboratory testing on blood sample drawn maximally 24 hours prior to randomization),
11. has any concurrent illness which, in the opinion of the investigator, may interfere with treatment or evaluation of safety or completion of this study,
12. has participated in another clinical trial of an investigational drug (including placebo) or device within 30 days (or the limit set by national law, whichever is longer) of signing informed consent for the present study,
13. has participated in any YM150 clinical trials,
14. has known allergy to the study drug or any of its components.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary outcome variable is the incidence at six months of Major and Clinically Relevant Non Major (CRNM) bleeding events according to the ISTH definition (Schulman, 2005) and as determined by the IAC. |
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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 | Yes |
| 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 | Yes |
| 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 | 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) | 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 200 |
| 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
| |
| 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 | 4 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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