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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00787150
First received: November 5, 2008
Last updated: April 23, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Drug: Apixaban
Drug: Warfarin sodium
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Total Bleeding Events During the Treatment Period [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Major (Per International Society on Thrombosis and Haemostasis [ISTH] Criteria) Bleeding Events During the Treatment Period [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Relevant Non-major Bleeding Events During the Treatment Period [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Stroke or Systemic Embolism During the Intended Treatment Period [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Stroke, Systemic Embolism, or All-Cause Death During the Intended Treatment Period [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Myocardial Infarction or All-Cause Death During the Intended Treatment Period [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Mean Plasma Apixaban Concentration at Each Time Point in Participants Treated With Apixaban [ Time Frame: 0, 2, 4 hours postdose at Week 1 and Week 8 ] [ Designated as safety issue: No ]
    Sample at 4 hours postdose was to be taken if possible.

  • Mean Prothrombin Time (PT) at Each Time Point in Participants Treated With Apixaban [ Time Frame: Week 0, 0, 2, 4 hours postdose at Week 1 and Week 8 ] [ Designated as safety issue: No ]
    Sample at 4 hours postdose was to be taken if possible.

  • Mean Prothrombin Time-International Normalized Ratio (PT-INR) at Each Time Point in Participants Treated With Apixaban [ Time Frame: Week 0, 0, 2, 4 hours postdose at Week 1 and Week 8 ] [ Designated as safety issue: No ]
    Blood sample at 4 hours postdose was collected if possible. PT-INR is a standardized measure derived from prothrombin time (PT). The systematic variations in PT assay results are corrected in PT-INR in order to optimize measurements of vitamin K antagonists.

  • Mean Activated Partial Thromboplastin Time (aPTT) at Each Time Point in Participants Treated With Apixaban [ Time Frame: Week 0, 0, 2, 4 hours postdose at Week 1 and Week 8 ] [ Designated as safety issue: No ]
    Blood Sample at 4 hours postdose was collected if possible. The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V, VIII, IX, X, XI and XII. Higher values than the baseline indicate anticoagulant effects.

  • Mean Anti-Xa Activity (Apixaban Units) at Each Time Point in Participants Treated With Apixaban [ Time Frame: Week 0, 0, 2, 4 hours postdose at Week 1 and Week 8 ] [ Designated as safety issue: No ]
    Blood sample at 4 hours postdose was collected if possible. Below the limit of quantification (BLQ) was assigned the value 0 for calculation. If 50% or more of the data was BLQ, statistics was not be calculated. Therefore, 0 means not calculated.

  • Mean Prothrombin Fragment 1+2 (F1+2) at Each Time Point in Participants Treated With Warfarin or Apixaban [ Time Frame: Week 0, Week 1, Week 8 ] [ Designated as safety issue: No ]
    Below the limit of quantification (BLQ) was assigned the value 0 for calculation. If 50% or more of the data was BLQ, statistics was not calculated. Therefore, 0 indicates not calculated.

  • Mean D-Dimer at Each Time Point in Participants Treated With Warfarin or Apixaban [ Time Frame: Week 0, Week 1, Week 8 ] [ Designated as safety issue: No ]
    Below the limit of quantification (BLQ) was assigned the value 0 for calculation.


Enrollment: 222
Study Start Date: June 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apixaban 5mg BID Drug: Apixaban
Apixaban 5 mg tablet BID for 12 weeks
Experimental: Apixaban 2.5mg BID Drug: Apixaban
Apixaban 2.5 mg tablet BID for 12 weeks
Active Comparator: Warfarin Drug: Warfarin sodium
At each visit, the subject to take appropriate Warfarin tablet (on investigator's order) once a day every morning for 12 weeks

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00787150

Locations
Japan
Pfizer Investigational Site
Nagoya, Aichi, Japan
Pfizer Investigational Site
Seto, Aichi, Japan
Pfizer Investigational Site
Touon, Ehime, Japan
Pfizer Investigational Site
Kitakyushu, Fukuoka, Japan
Pfizer Investigational Site
Ogaki, Gifu, Japan
Pfizer Investigational Site
Isezaki, Gunma, Japan
Pfizer Investigational Site
Shibukawa, Gunma, Japan
Pfizer Investigational Site
Sapporo, Hokkaido, Japan
Pfizer Investigational Site
Higashiibaraki-gunn Ibarakimachi, Ibaraki, Japan
Pfizer Investigational Site
Zentsuji, Kagawa, Japan
Pfizer Investigational Site
Kawasaki, Kanagawa, Japan
Pfizer Investigational Site
Tsu, Mie, Japan
Pfizer Investigational Site
Minato-ku, Tokyo, Japan
Pfizer Investigational Site
Shinagawa-ku, Tokyo, Japan
Pfizer Investigational Site
Shinjuku-ku, Tokyo, Japan
Pfizer Investigational Site
Iwakuni, Yamaguchi, Japan
Pfizer Investigational Site
Fukuoka, Japan
Pfizer Investigational Site
Kumamoto, Japan
Sponsors and Collaborators
Pfizer
Bristol-Myers Squibb
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00787150     History of Changes
Other Study ID Numbers: B0661003
Study First Received: November 5, 2008
Results First Received: January 29, 2013
Last Updated: April 23, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014