A Study to Evaluate the Safety of Apixaban in Acute Coronary Syndrome (ACS) Japanese Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess the bleeding safety (the composite endpoint of major and clinically relevant non-major bleeding) of 2 doses of apixaban (2.5 mg BID and 5.0 mg BID) or placebo in combination with standard therapy (aspirin and /or additional antiplatelet therapy) over a 24 week treatment period in selected subjects with recent (≤7 days) acute coronary syndrome.

Detailed Description
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Due to withdraw of global phase 3 study (APPRAISE-2) for safety issue, B0661004 Data monitoring committee (DMC) also recommended terminating this study. Therefore, Pfizer decided to stop this study.

Official Title
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A Phase 2, Placebo-Controlled, Randomized, Double-Blinded, Multicenter, Study To Evaluate The Bleeding Profile Of 2.5 Mg And 5.0 Mg BID Apixaban In Combination With Standard Therapy In Patients With Recent (≤7 Days) Acute Coronary Syndrome (ACS)

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Apixaban
* Drug: Apixaban
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recent (≤ 7 days) ACS Clinically stable, and receiving standard treatment (patients must be treated with aspirin ≤ 100 mg/day, with or without clopidogrel 75 mg/day or ticlopidine 200 mg/day) based on the physician's judgment) Exclusion Criteria: Scheduled/planned cardiac catheterization, PCI, CABG or other invasive procedure planned in the 24 weeks (within treatment period) following randomization Persistent severe hypertension, defined as systolic blood pressure of ≥180 mm Hg or diastolic pressure of ≥110 mm Hg Active bleeding or at high risk for bleeding (e.g., cirrhosis of the liver, any history of intracranial hemorrhage).

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 2.5 mg<br> | Drug: Apixaban<br>* Apixaban 2.5 mg tablet BID for 24 weeks<br>|
| Experimental: Apixaban 5.0 mg<br> | Drug: Apixaban<br>* Apixaban 5.0 mg tablet BID for 24 weeks<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo tablet for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had Composite of International Society on Thrombosis and Haemostasis (ISTH)-Defined Major and Clinically-relevant Non-major (CRNM) Bleeding Events Occurring 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. CRNM bleeding was acute or sub-acute clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy. | Week 0 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had One or More All Bleeding Occurring During the Treatment Period. | All bleeding included major bleeding (including fatal bleeding), clinically-relevant non-major (CRNM) bleeding, and minor bleeding per international society on thrombosis and haemostasis (ISTH) definitions. | Week 0 to Week 24 | 
| Percentage of Participants Who Had Major Bleeding Occurring During the Treatment Period Per International Society on Thrombosis and Haemostasis (ISTH) Definitions. | Major bleeding event was defined as an 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 occured in critical site (e.g., intracranial). Fatal bleeding was also major bleeding event. | Week 0 to Week 24 | 
| Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI)-Defined Major Bleeding Occurring During the Treatment Period. | TIMI major bleeding event was difined as an intracranial bleeding or clinically overt bleeding (including bleeding evident on imaging studies) associated with a >= 5 gm/dL fall in hemoglobin or a 15% fall in hematocrit from baseline, accounting for the effect of transfusions (1 unit packed red blood cells = 1 gm/dL hemoglobin = 3% hematocrit). | Week 0 to Week 24 | 
| Percentage of Participants Who Had Composite of All-cause Death, Non-fatal Myocardial Infarction, Unstable Angina and Stroke During 30 Days After Discontinuation of Therapy. |  | For 30 days after Week 24 or the discontinuation of study drug | 
| Percentage of Participants Who Had Composite of All-cause Death, Non-fatal Myocardial Infarction (MI), Unstable Angina, and Non-hemorrhagic Stroke Occurring During the Intended Treatment Period. | Intended treatment period for efficacy endpoints was defined as a period starting on the day of randomization and ending at the later date of either 2-days after the last dose of study drug or Day 168/Week 24 after randomization day (or the study termination date [19 November 2010, Japan time]). | From the day of randomization to the later date of either 2-days after the last dose of study drug or Day 168/Week 24 after randomization day (or the study termination date [19 November 2010, Japan time]) |