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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

November 5, 2008
April 23, 2013
June 2008
September 2009   (final data collection date for primary outcome measure)
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.
Incidence of adjudicated major or clinically relevant non-major bleeding during the treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00787150 on ClinicalTrials.gov Archive Site
  • 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.
  • Incidence of adjudicated myocardial infarction or all-cause death during the treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of major bleeding during the treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Other safety outcome measures will also be assessed, including serious and non-serious AEs and changes in standard clinical laboratory test results [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adjudicated stroke or systemic embolism during the treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adjudicated stroke, systemic embolism or all-cause death during the treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of total bleeding (major bleeding, clinically relevant non-major bleeding, and minor bleeding) during the treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • 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.
Not Provided
 
A Phase 2 Study To Evaluate The Safety Of Apixaban In Atrial Fibrillation
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Atrial Fibrillation
  • Drug: Apixaban
    Apixaban 5 mg tablet BID for 12 weeks
  • Drug: Apixaban
    Apixaban 2.5 mg tablet BID for 12 weeks
  • 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
  • Experimental: Apixaban 5mg BID
    Intervention: Drug: Apixaban
  • Experimental: Apixaban 2.5mg BID
    Intervention: Drug: Apixaban
  • Active Comparator: Warfarin
    Intervention: Drug: Warfarin sodium
Ogawa S, Shinohara Y, Kanmuri K. Safety and efficacy of the oral direct factor xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. -The ARISTOTLE-J study-. Circ J. 2011;75(8):1852-9. Epub 2011 Jun 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
222
September 2009
September 2009   (final data collection date for primary outcome measure)

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.
Both
20 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00787150
B0661003
Yes
Pfizer
Pfizer
Bristol-Myers Squibb
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP