DU-176b Phase 2 Dose Finding Study in Subjects With Non-valvular Atrial Fibrillation

Study Overview
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Brief Summary
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This study will be conducted in male and female subjects aged 18 to 80 years, inclusive, with non-valvular AF and a CHADS2 Score of at least 1. Subjects will be treated on an outpatient basis. The subjects will be allocated randomly to the open-label warfarin or any double-blind DU-176b dosages. DU-176b will be administered orally for 12 weeks at two fixed doses. Warfarin will be used as active control. Warfarin dosing will be managed and monitored by the Investigator with the dose adjusted to achieve an INR of 2.0 to 3.0, inclusive. The primary endpoints are incidence of major, clinically relevant non-major and minor bleeding events (all bleeding).

Official Title
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A Phase 2, Randomized, Parallel Group, Multi-Center, Multi-National Study for the Evaluation of Safety and Efficacy of Two Fixed Dosages of DU-176b in Subjects With Non-Valvular Atrial Fibrillation

Conditions
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Atrial Fibrillation, Stroke

Intervention / Treatment
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* Drug: DU-176b tablets
* Drug: DU-176b tablets
* Drug: Warfarin tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 18 to 80 years of age Non-valvular AF supported by abnormal ECG documented for two times (interval of more than 1 week) within 6 months prior to randomization. CHADS2 Score of at least 1. Exclusion Criteria: Subjects with mitral valve disease Subjects with previous valvular heart surgery Contraindication for anticoagulants Conditions associated with high risk of bleeding Acute coronary syndromes (ACS), percutaneous coronary intervention (PCI), MI, stroke, transient ischemic attack (TIA) or coronary artery/cardiac/other major surgery within the previous 30 days Active infective endocarditis or life-expectancy < 12 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: 2<br>DU-176b tablets: high-dose | Drug: DU-176b tablets<br>* DU-176b tablets taken once daily for up to 3 months<br>|
| Active Comparator: 3<br>Warfarin tablets | Drug: Warfarin tablets<br>* Warfarin tablets taken once daily for up to 3 months<br>|
| Experimental: 1<br>DU-176b tablets: low-dose | Drug: DU-176b tablets<br>* DU-176b tablets taken once daily for up to 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of All Bleeding | Incidence of all bleeding (major, clinically relevant non-major and minor) in two fixed dosage of DU-176b in comparison with warfarin as active control in subjects with non-valvular AF. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Incidence of Major Adverse Cardiovascular Events: Stroke, Systemic Embolic Event, Myocardial Infarction, Cardiovascular Death, and Hospitalization for Any Cardiac Condition |  | 6 months | 
| Evaluation of Effects on Biomarkers of Thrombus Formation |  | 6 months | 
| Evaluation of Plasma Concentration of DU-176 |  | 6 months | 
| Evaluation of Effects on Pharmacodynamic Biomarkers |  | 6 months | 
| Evaluation of All Clinical and Laboratory Safety Data. |  | 6 months |