Safety Study of Apixaban in Recent Acute Coronary Syndrome

Study Overview
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Brief Summary
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The purpose of this clinical research study is to determine whether apixaban will be safe in people who have recently had unstable angina or a heart attack.

Official Title
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A Phase 2, Placebo-Controlled, Randomized, Double Blind, Parallel Arm, Dose Ranging Study to Evaluate Safety and Efficacy of Apixaban in Patients With a Recent Acute Coronary Syndrome.

Conditions
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Acute Coronary Syndrome (ACS)

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Recent (< = 7 days) Acute Coronary Syndrome (ACS). Clinically stable on optimal treatment Key Exclusion Criteria: High bleeding risk. Ongoing anticoagulant use. Need for chronic (>3 months) daily nonsteroidal anti-inflammatory drug (NSAID) or chronic high dose acetylsalicylic acid (ASA) use (>325 mg/day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A1<br> | Drug: Apixaban<br>* Tablets, Oral, 2.5 mg, twice daily, 26 weeks<br>|
| Experimental: A2<br> | Drug: Apixaban<br>* Tablets, Oral, 10 mg, once daily, 26 weeks<br>|
| Placebo Comparator: A3<br> | Drug: Placebo<br>* Tablets, Oral, 0, twice daily, 26 weeks<br>|
| Experimental: A4<br> | Drug: Apixaban<br>* Tablets, Oral 10 mg, twice daily, 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The primary outcome is based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B. The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups (10mg BID, 20mg QD) and the resulting lower duration of exposure for these groups. | From first dose of study drug (Day 1) to last dose plus 2 days, up to Year 2 of the Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | Events were adjudicated by the Clinical Events Committee (CEC). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B. | Randomization to 182 days after randomization (183 days) | 
| Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses | Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events includes major bleeding, clinically relevant non-major bleeding and minor bleeding. Treatment Period refers to the period from first dose through 2 days, or through 30 days for Serious Adverse Event (SAE) tabulations, after discontinuation of study drug. Data in this outcome are combined across Phase A and Phase B. | first dose (Day 1) to last dose plus 2 days (or for SAEs, plus 30 days), up to Year 2 of the Study | 
| Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants | Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B | Day of randomization to 182 days after day of randomization (183 days) | 
| Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses | Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the Clinical Events Committee. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). | from first dose (Day 1) to last dose plus 2 days, up to Year 2 of the Study | 
| Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | Phase B Adjusted Intended Treatment Period=day of randomization and ends on termination date of high dose apixaban, 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure. | Day of randomization and ends on high dose termination date, 1-Oct-2007 | 
| Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B | Bleeding was assessed using ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups and the lower duration of exposure. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group). | From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007 | 
| Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events included major bleeding, clinically relevant non-major bleeding and minor bleeding. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group). | From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007 | 
| Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B | Phase B Adjusted Intended Treatment Period=day of randomization and ends on 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure. | Day of randomization up to high dose termination, 1-Oct-2007 | 
| Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B | Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). | From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007 |