A Study Evaluating Safety and Tolerability of YM150 Compared to Warfarin in Subjects With Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study is to investigate the optimal daily dose and dose regimen of YM150 in subjects with non-valvular atrial fibrillation (NVAF), primarily based on safety and tolerability data.

Official Title
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A Phase 2, Double-Blind, Double-Dummy, Randomized, Parallel Group Dose Finding Study To Investigate the Safety and Tolerability of YM150 in Subjects With Non-Valvular Atrial Fibrillation and to Compare the Safety and Tolerability With Warfarin

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: YM150
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with paroxysmal, permanent or persistent Nonvalvular Atrial Fibrillation (NVAF) Subject has prothrombin time international normalized ratio (INR) of 2.0 or below at the baseline visit Exclusion Criteria: Subject has current or recent (within 12 months prior to screening) history of stroke and/or systemic embolism (including TIA) Subject has active bleeding or any condition associated with increased risk of bleeding Subject has NVAF secondary to other reversible disorders (e.g. thyrotoxicosis) Subject has an indication for warfarin other than AF (including planned cardioversion) 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 Subject has a diagnosis of left ventricular aneurysm or atrial myxoma 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) Subject has active infective endocarditis Subject is planned for invasive procedures with potential for bleeding 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 Subject has participated in any YM150 clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. YM150, Dose W, twice daily<br> | Drug: YM150<br>* oral<br>|
| Experimental: 2. YM150, Dose X, once daily<br> | Drug: YM150<br>* oral<br>|
| Experimental: 3. YM150, Dose X, twice daily<br> | Drug: YM150<br>* oral<br>|
| Experimental: 4. YM150, Dose Y once daily<br> | Drug: YM150<br>* oral<br>|
| Experimental: 5. YM150, Dose Y twice daily<br> | Drug: YM150<br>* oral<br>|
| Experimental: 6. YM150, Dose Z, once daily<br> | Drug: YM150<br>* oral<br>|
| Active Comparator: 7. Warfarin<br> | Drug: Warfarin<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major and clinically relevant non-major bleeding events |  | Double-blind treatment period (variable, up to 16 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite and individual incidences of ischemic strokes, TIAs, systemic thrombolic events, ACS, all deaths |  | Double-blind treatment period (variable, up to 16 months) | 
| Incidence of bleeding events |  | Double-blind treatment period (variable, up to 16 months) | 
| Assessment of other safety variables |  | Double blind treatment period (variable, up to 16 months) | 
| Assessment of PK/PD variables |  | Double-blind treatment period (up to week 12) | 
| Patient Reported Outcomes |  | Double-blind treatment period (up to week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonvalvular Atrial Fibrillation (NVAF), Factor Xa Inhibitor, Stroke, Thromboembolism, Transient Ischemic attack, Anticoagulants, Prevention, YM150, Warfarin