A Phase 2 Study To Evaluate The Safety Of Apixaban In Atrial Fibrillation

Study Overview
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Brief Summary
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To assess the effect of two doses of Apixaban (2.5 mg BID and 5 mg BID) versus Warfarin on the composite endpoint of major and clinically relevant non-major bleeding during the treatment period.

Official Title
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A Phase 2b, Randomized, Partially Blind (Open Label Warfarin), Active-Controlled (Warfarin), Multicenter Study, To Evaluate The Safety And Efficacy In 2 Doses Of Apixaban In Comparison To Warfarin, Administered For 12 Weeks In Subjects With NVAF

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Apixaban
* Drug: Apixaban
* Drug: Warfarin sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 20 years outpatient (regardless of sex) Patients diagnosed as non-valvular atrial fibrillation (NVAF) One or more following risks of stroke. Exclusion Criteria: Recent cerebral infarction (includes TIA) within 4 weeks of week 0. Subjects who have or are suspected to have a serious/hereditary bleeding tendency, such as disseminated intravascular coagulation syndrome (DIC), congenital platelet dysfunction and von Willebrand disease (those suspected from the family history are included). Subjects who have or are suspected to have a serious/hereditary thrombogenic tendency (those suspected from the family history are included) or those who require continuation of the Warfarin therapy.

Ages Eligible for Study
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Minimum Age: 20 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban 5mg BID<br> | Drug: Apixaban<br>* Apixaban 5 mg tablet BID for 12 weeks<br>|
| Experimental: Apixaban 2.5mg BID<br> | Drug: Apixaban<br>* Apixaban 2.5 mg tablet BID for 12 weeks<br>|
| Active Comparator: Warfarin<br> | Drug: Warfarin sodium<br>* At each visit, the subject to take appropriate Warfarin tablet (on investigator's order) once a day every morning for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major (Per International Society on Thrombosis and Haemostasis [ISTH] Criteria) or Clinically Relevant Non-major Bleeding Adjudicated by Clinical Event Committee During the Treatment Period | Major bleeding event was acute clinically overt bleeding accompanied by decrease in hemoglobin of 2 g/dL or more over a 24-hour period, transfusion of 2 or more units of packed red blood cells, or bleeding that occurs in critical site (e.g., intracranial). Fatal bleeding was also major bleeding event. Clinical relevant non-major bleeding was acute or sub-acute clinically overt bleeding that does not satisfy the criteria for major bleeding and that leads to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Total Bleeding Events During the Treatment Period | Total bleeding events consisted of major (per International Society on Thrombosis and Haemostasis [ISTH] Criteria), clinically relevant non-major and minor bleeding events. All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding were classified as minor bleeding. | Baseline to Week 12 | 
| Number of Participants With Major (Per International Society on Thrombosis and Haemostasis [ISTH] Criteria) Bleeding Events During the Treatment Period | Major bleeding event is acute clinically overt bleeding accompanied by decrease in hemoglobin of 2 g/dL or more over a 24-hour period, transfusion of 2 or more units of packed red blood cells, or bleeding that occurs in critical site (e.g., intracranial). Fatal bleeding is also major bleeding event. | Baseline to Week 12 | 
| Number of Participants With Clinically Relevant Non-major Bleeding Events During the Treatment Period | Clinical relevant non-major bleeding was acute or sub-acute clinically overt bleeding that does not satisfy the criteria for major bleeding and that leads to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy. | Baseline to Week 12 | 
| Number of Participants With Stroke or Systemic Embolism During the Intended Treatment Period | The definition of the Intended Treatment Period was the period starting on the day of randomization and ending at the later one of either 2 days after the last dose of the study drug or Day 85/Week 12 after the randomization day. | Baseline to Week 12 | 
| Number of Participants With Stroke, Systemic Embolism, or All-Cause Death During the Intended Treatment Period | The definition of the Intended Treatment Period was the period starting on the day of randomization and ending at the later one of either 2 days after the last dose of the study drug or Day 85/Week 12 after the randomization day. | Baseline to Week 12 | 
| Number of Participants With Myocardial Infarction or All-Cause Death During the Intended Treatment Period | The definition of the Intended Treatment Period was the period starting on the day of randomization and ending at the later one of either 2 days after the last dose of the study drug or Day 85/Week 12 after the randomization day. | Baseline to Week 12 |