the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF) MedDRA version: 9.1 Level: LLT Classification code 10049165 Term: Cerebrovascular accident prophylaxis
Conditions
Interventions
Product Name: YM150
Product Code: YM150
Pharmaceutical Form: Tablet
Current Sponsor code: YM150
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical f
Sponsors
Astellas Pharma Europe B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject is eligible for the study if all of the following apply: 1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written Informed Consent prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Male or female subject 18 years of age (legal minimum age required per country) or older at time of informed consent. 3. Subject has paroxysmal NVAF (had 2 or more episodes of AF which terminated spontaneously documented by ECG or rhythm strip and clinical history before study screening visit), persistent NVAF (AF of more than 7 days documented by either ECG, rhythm strip or a 24-hour Holter monitor before study screening visit), or permanent NVAF (long-standing AF present at study screening visit in which previous cardioversion has failed or has been foregone). 4. Subject has prothrombin time international normalized ratio (INR) of 2.0 or below at the baseline visit. 5. Subject has CHADS2 stroke risk stratification score of 1 to 6 (see Appendix 3) at screening visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subject will be excluded from participation if any of the following apply: 1. Female subject 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. 2. Female subject who is pregnant or lactating or has a positive pregnancy test within 72 hours prior to randomization. 3. Subject has current or recent (within 12 months prior to screening) history of stroke and/or systemic embolism (including TIA). 4. Subject has active bleeding or any condition associated with increased risk of bleeding. 5. Subject has NVAF secondary to other reversible disorders (e.g. thyrotoxicosis). 6. Subject has an indication for warfarin other than AF (including planned cardioversion). 7. Subject has had a diagnosis of Acute Coronary Syndrome (ACS), coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) within previous 3 months of screening. 8. Subject has a diagnosis of left ventricular aneurysm or atrial myxoma. 9. Subject requires use of prohibited previous and concomitant medication. (i.e., thrombolytics [such as tissue Plasminogen Activator (tPA), streptokinase], antiplatelet agents [such as cilostazol, clopidogrel, ticlopidine, dipyridamole], anticoagulants [such as vitamin K antagonists, heparin, unfractionated or low molecular weight heparin, fondaparinux, thrombin inhibitors] and chronic use of nonsteroidal anti-inflammatory drugs [NSAIDs] or acetylsalicylic acid use of >100 mg/day). (see Section 5.1.3 and Appendix 1 for details) 10. Subject has a renal creatinine clearance of 2 times the upper limit of normal (ULN) or total bilirubin > 1.5 times the ULN at screening. 12. Subject has active infective endocarditis. 13. Subject has persistent blood pressure of 160 mmHg systolic or higher and/or 100 mmHg diastolic or higher at baseline with or without medication. 14. Subject has hemoglobin <10 g/dL or platelet count <100,000/µL at screening. 15. Subject has any contraindications to warfarin. 16. Subject is planned for invasive procedures with potential for bleeding. 17. Subject has any concurrent illness which, in the opinion of the Investigator, may interfere with treatment or evaluation of safety or completion of this study. 18. Subject 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. 19. Subject has participated in any YM150 clinical trials.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate the optimal daily dose and dose regimen of YM150 in subjects with NVAF, primarily based on safety and tolerability data. ;Secondary Objective: Secondary objectives are - to obtain information on pharmacokinetics and pharmacodynamics (antithrombotic potential) in the target population, - to evaluate the efficacy, safety and tolerability of YM150 in subjects with NVAF and - to evaluate the effects of YM150 and warfarin on: [1] the health status of subjects with NVAF; [2] the number of Quality Adjusted Life Years (QALYs) gained (as a means of quantifying the benefit of the intervention); and [3] the health care resource use associated with both treatment options. ;Primary end point(s): The primary variable is the incidence of major and clinically relevant non-major bleeding events during the double blind treatment period as determined by the AC. All overt bleeding events will be reported by the Investigator and adjudicated and classified by an AC to major, clinically relevant non-major and minor bleeding events. Details on the adjudication process are described in the AC Charter. The classifications of bleeding events are listed in the proocol. All bleeding events will be reported via AE reporting and through specific questions at each visit and will be sent to the AC. | — |
Countries
Austria, Bulgaria, Czech Republic, Estonia, France, Germany, Hungary, Latvia, Spain, United Kingdom
Outcome results
None listed