Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A PHASE 2, RANDOMIZED, PARALLEL GROUP, DOSE-FINDING, MULTICENTER, MULTINATIONAL STUDY OF THE SAFETY, TOLERABILITY AND PILOT EFFICACY OF THREE BLINDED DOSES OF THE ORAL FACTOR Xa INHIBITOR BETRIXABAN COMPARED WITH OPEN- LABEL, DOSE-ADJUSTED WARFARIN IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

    Summary
    EudraCT number
    		 2008-005977-37
    Trial protocol
    		 DE  
    Global end of trial date
    05 Nov 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Dec 2017
    First version publication date
    28 Dec 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    08-015
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00742859
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Portola Pharmaceuticals, Inc.
    Sponsor organisation address
    270 East Grand Avenue, South San Francisco, United States, 94080
    Public contact
    Janice Castillo, Portola Pharmaceuticals, Inc., 001 650-246-7360,
    Scientific contact
    Janice Castillo, Portola Pharmaceuticals, Inc., 001 650-246-7360,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Jul 2012
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Aug 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Nov 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the trial is to assess the safety and tolerability of betrixaban at doses of 40 mg, 60 mg and 80 mg given orally once a day for at least 3 months compared to a dose-adjusted Vitamin K antagonist in patients with non-valvular AF.
    Protection of trial subjects
    The conduct of this clinical study met local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Oct 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    United States: 369
    Country: Number of subjects enrolled
    Canada: 127
    Worldwide total number of subjects
    508
    EEA total number of subjects
    12
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    81
    From 65 to 84 years
    397
    85 years and over
    30

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Between 31 October 2008 and 05 November 2009, 508 patients were enrolled by 35 study centers in 3 countries (USA, Canada, Germany). Patients were randomized to 1 of 4 treatment groups (1:1:1:1 allocation). The study was open-label for warfarin, while the 3 daily doses of betrixaban (40, 60, or 80 mg) were double-blinded.

    Pre-assignment
    Screening details
    		 561 patients were screened for study participation. Of these patients, 508 were randomized, all of whom received at least 1 dose of study drug.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Betrixaban 40 mg
    Arm description
    		 Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months
    Arm type
    		 Experimental

    Investigational medicinal product name
    Betrixaban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months

    Arm title
    		 Betrixaban 60 mg
    Arm description
    		 Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months
    Arm type
    		 Experimental

    Investigational medicinal product name
    Betrixaban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months

    Arm title
    		 Betrixaban 80 mg
    Arm description
    		 Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months
    Arm type
    		 Experimental

    Investigational medicinal product name
    Betrixaban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months

    Arm title
    		 Warfarin
    Arm description
    		 Dose-adjusted warfarin to maintain an INR of 2.0 to 3.0 with INR measured at maximum intervals of 4 weeks. Treatment duration was at least 3 months and no longer than approximately 11 months
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Warfarin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dose-adjusted warfarin to maintain an INR of 2.0 to 3.0 with INR measured at maximum intervals of 4 weeks. Treatment duration was at least 3 months and no longer than approximately 11 months

    Number of subjects in period 1
    		Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
    Started
    127
    127
    127
    127
    Completed
    116
    115
    116
    119
    Not completed
    11
    12
    11
    8
         Adverse event, serious fatal
    1
    -
    -
    1
         Physician decision
    1
    2
    -
    -
         Consent withdrawn by subject
    4
    2
    4
    1
         Amendment 2 Pt off Study Drug for >4 weeks
    -
    1
    1
    -
         Adverse event, non-fatal
    5
    6
    3
    1
         Sponsor request visit schedule noncompliance
    -
    -
    -
    1
         Sponsor request PT out of town
    -
    -
    1
    1
         Site Error
    -
    -
    1
    1
         Endpoint
    -
    1
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Betrixaban 40 mg
    Reporting group description
    		 Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Betrixaban 60 mg
    Reporting group description
    		 Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Betrixaban 80 mg
    Reporting group description
    		 Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Warfarin
    Reporting group description
    		 Dose-adjusted warfarin to maintain an INR of 2.0 to 3.0 with INR measured at maximum intervals of 4 weeks. Treatment duration was at least 3 months and no longer than approximately 11 months

    Reporting group values
    		 Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin Total
    Number of subjects
    		 127 127 127 127 508
    Age categorical
    All randomized patients who took at least 1 dose of study medication after randomization.
    Units: Subjects
        <=64 years
    		 21 19 22 19 81
        65<=age<85 years
    		 97 96 100 104 397
        age >=85 years
    		 9 12 5 4 30
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 73.3 ( 8.5 ) 73.8 ( 8.35 ) 72.0 ( 7.65 ) 72.7 ( 8.75 ) -
    Gender categorical
    All randomized patients who took at least 1 dose of study medication after randomization.
    Units: Subjects
        Female
    		 79 81 89 89 338
        Male
    		 48 46 38 38 170

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Betrixaban 40 mg
    Reporting group description
    		 Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Betrixaban 60 mg
    Reporting group description
    		 Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Betrixaban 80 mg
    Reporting group description
    		 Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Warfarin
    Reporting group description
    		 Dose-adjusted warfarin to maintain an INR of 2.0 to 3.0 with INR measured at maximum intervals of 4 weeks. Treatment duration was at least 3 months and no longer than approximately 11 months

    Primary: Exposure-adjusted incidence rate of major or clinically relevant non-major bleeding episode

    		 Close Top of page
    End point title
    		 Exposure-adjusted incidence rate of major or clinically relevant non-major bleeding episode
    End point description
    The primary endpoint is the time to the first occurrence of major or clinically relevant non-major bleeding. This was presented as the exposure adjusted incidence rate which was calculated as number of subjects experiencing the event divided by total person years across all subjects, where if a patient experiencing the event, year was from first dose date to the first occurrence of the event, and to last study date if not. The confidence interval was calculated via the exact Poisson distribution.
    End point type
    Primary
    End point timeframe
    A maximum of 1 year
    End point values
    		 Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
    Number of subjects analysed
    127
    127
    127
    127
    Units: Number of Participants
        number (confidence interval 95%)
    2.02 (0.05 to 11.3)
    10.1 (3.28 to 23.6)
    10.5 (3.41 to 24.5)
    14.6 (5.85 to 30.0)
    Statistical analysis title
    		 Betrixaban 40 mg
    Statistical analysis description
    Incidence rate indicating the number of patients reporting events per 100 patient years. 95% CI was calculated via exact method assuming Poisson distribution.
    Comparison groups
    Warfarin v Betrixaban 40 mg
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.035
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.017
         upper limit
    		 1.14
    Statistical analysis title
    		 Betrixaban 60 mg
    Comparison groups
    Warfarin v Betrixaban 60 mg
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.546
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.711
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.225
         upper limit
    		 2.24
    Statistical analysis title
    		 Betrixaban 80 mg
    Comparison groups
    Warfarin v Betrixaban 80 mg
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.712
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.755
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.239
         upper limit
    		 2.39

    Secondary: Exposure-adjusted incidence rate of any bleeding (major, clinically relevant non-major, or minimal)

    		 Close Top of page
    End point title
    		 Exposure-adjusted incidence rate of any bleeding (major, clinically relevant non-major, or minimal)
    End point description
    The time to the first occurrence of any bleeding event. This was presented as the exposure adjusted incidence rate which was calculated as number of subjects experiencing the event divided by total person years across all subjects, where if a patient experiencing the event, year was from first dose date to the first occurrence of the event, and to last study date if not. The confidence interval was calculated via the exact Poisson distribution.
    End point type
    Secondary
    End point timeframe
    A maximum of 1 year
    End point values
    		 Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
    Number of subjects analysed
    127
    127
    127
    127
    Units: number of patients per 100 patient years
        number (confidence interval 95%)
    50.5 (31.7 to 76.5)
    77.9 (53.3 to 110)
    56.0 (35.9 to 83.4)
    103 (73.6 to 140)
    Statistical analysis title
    		 Betrixaban 40 mg
    Statistical analysis description
    Incidence rate indicating the number of patients reporting events per 100 patient years. 95% CI was calculated via exact method assuming Poisson distribution.
    Comparison groups
    Warfarin v Betrixaban 40 mg
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.011
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.508
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.301
         upper limit
    		 0.856
    Statistical analysis title
    		 Betrixaban 60 mg
    Statistical analysis description
    Incidence rate indicating the number of patients reporting events per 100 patient years. 95% CI was calculated via exact method assuming Poisson distribution.
    Comparison groups
    Warfarin v Betrixaban 60 mg
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.308
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.767
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.481
         upper limit
    		 1.22
    Statistical analysis title
    		 Betrixaban 80 mg
    Statistical analysis description
    Incidence rate indicating the number of patients reporting events per 100 patient years. 95% CI was calculated via exact method assuming Poisson distribution.
    Comparison groups
    Warfarin v Betrixaban 80 mg
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.022
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.551
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.332
         upper limit
    		 0.914

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose date (including) till the end of study
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Betrixaban 40 mg
    Reporting group description
    		 Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Betrixaban 60 mg
    Reporting group description
    		 Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Betrixaban 80 mg
    Reporting group description
    		 Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months

    Reporting group title
    Warfarin
    Reporting group description
    		 Dose-adjusted warfarin to maintain an INR of 2.0 to 3.0 with INR measured at maximum intervals of 4 weeks. Treatment duration was at least 3 months and no longer than approximately 11 months

    Serious adverse events
    		 Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 127 (9.45%)
    12 / 127 (9.45%)
    11 / 127 (8.66%)
    12 / 127 (9.45%)
         number of deaths (all causes)
    0
    0
    2
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac neoplasm unspecified
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer recurrent
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatic obstruction
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 127 (0.79%)
    1 / 127 (0.79%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Hallucination
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    International normalised ratio increased
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    3 / 127 (2.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    1 / 127 (0.79%)
    1 / 127 (0.79%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia obstructive
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament disorder
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 127 (0.79%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 127 (0.00%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    61 / 127 (48.03%)
    68 / 127 (53.54%)
    53 / 127 (41.73%)
    50 / 127 (39.37%)
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    1 / 127 (0.79%)
    4 / 127 (3.15%)
    0 / 127 (0.00%)
    3 / 127 (2.36%)
         occurrences all number
    1
    5
    0
    3
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 127 (2.36%)
    3 / 127 (2.36%)
    1 / 127 (0.79%)
    4 / 127 (3.15%)
         occurrences all number
    3
    3
    1
    4
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 127 (0.79%)
    0 / 127 (0.00%)
    1 / 127 (0.79%)
    4 / 127 (3.15%)
         occurrences all number
    2
    0
    2
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    12 / 127 (9.45%)
    9 / 127 (7.09%)
    6 / 127 (4.72%)
    3 / 127 (2.36%)
         occurrences all number
    12
    11
    6
    3
    Headache
         subjects affected / exposed
    5 / 127 (3.94%)
    6 / 127 (4.72%)
    9 / 127 (7.09%)
    3 / 127 (2.36%)
         occurrences all number
    6
    6
    9
    3
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    5 / 127 (3.94%)
    1 / 127 (0.79%)
    2 / 127 (1.57%)
    3 / 127 (2.36%)
         occurrences all number
    5
    1
    2
    3
    Fatigue
         subjects affected / exposed
    7 / 127 (5.51%)
    5 / 127 (3.94%)
    4 / 127 (3.15%)
    4 / 127 (3.15%)
         occurrences all number
    7
    6
    4
    4
    Oedema peripheral
         subjects affected / exposed
    8 / 127 (6.30%)
    10 / 127 (7.87%)
    6 / 127 (4.72%)
    11 / 127 (8.66%)
         occurrences all number
    8
    11
    7
    12
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 127 (1.57%)
    5 / 127 (3.94%)
    2 / 127 (1.57%)
    1 / 127 (0.79%)
         occurrences all number
    2
    5
    2
    1
    Constipation
         subjects affected / exposed
    9 / 127 (7.09%)
    8 / 127 (6.30%)
    3 / 127 (2.36%)
    3 / 127 (2.36%)
         occurrences all number
    10
    8
    3
    3
    Diarrhoea
         subjects affected / exposed
    4 / 127 (3.15%)
    10 / 127 (7.87%)
    9 / 127 (7.09%)
    1 / 127 (0.79%)
         occurrences all number
    4
    11
    11
    1
    Dyspepsia
         subjects affected / exposed
    7 / 127 (5.51%)
    0 / 127 (0.00%)
    4 / 127 (3.15%)
    1 / 127 (0.79%)
         occurrences all number
    7
    0
    4
    1
    Nausea
         subjects affected / exposed
    2 / 127 (1.57%)
    5 / 127 (3.94%)
    14 / 127 (11.02%)
    2 / 127 (1.57%)
         occurrences all number
    2
    5
    15
    2
    Vomiting
         subjects affected / exposed
    1 / 127 (0.79%)
    2 / 127 (1.57%)
    6 / 127 (4.72%)
    1 / 127 (0.79%)
         occurrences all number
    1
    2
    6
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 127 (2.36%)
    8 / 127 (6.30%)
    3 / 127 (2.36%)
    3 / 127 (2.36%)
         occurrences all number
    3
    8
    3
    3
    Dyspnoea
         subjects affected / exposed
    4 / 127 (3.15%)
    3 / 127 (2.36%)
    5 / 127 (3.94%)
    2 / 127 (1.57%)
         occurrences all number
    4
    3
    5
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    4 / 127 (3.15%)
    3 / 127 (2.36%)
    3 / 127 (2.36%)
    1 / 127 (0.79%)
         occurrences all number
    4
    3
    3
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 127 (1.57%)
    4 / 127 (3.15%)
    5 / 127 (3.94%)
    0 / 127 (0.00%)
         occurrences all number
    3
    4
    5
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 127 (2.36%)
    6 / 127 (4.72%)
    3 / 127 (2.36%)
    4 / 127 (3.15%)
         occurrences all number
    5
    6
    3
    4
    Back pain
         subjects affected / exposed
    5 / 127 (3.94%)
    6 / 127 (4.72%)
    6 / 127 (4.72%)
    2 / 127 (1.57%)
         occurrences all number
    5
    6
    6
    2
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 127 (0.79%)
    2 / 127 (1.57%)
    4 / 127 (3.15%)
    0 / 127 (0.00%)
         occurrences all number
    1
    2
    4
    0
    Influenza
         subjects affected / exposed
    2 / 127 (1.57%)
    1 / 127 (0.79%)
    4 / 127 (3.15%)
    1 / 127 (0.79%)
         occurrences all number
    2
    1
    4
    1
    Nasopharyngitis
         subjects affected / exposed
    5 / 127 (3.94%)
    5 / 127 (3.94%)
    3 / 127 (2.36%)
    10 / 127 (7.87%)
         occurrences all number
    6
    5
    4
    11
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 127 (3.94%)
    1 / 127 (0.79%)
    4 / 127 (3.15%)
    3 / 127 (2.36%)
         occurrences all number
    7
    1
    4
    3
    Urinary tract infection
         subjects affected / exposed
    3 / 127 (2.36%)
    1 / 127 (0.79%)
    2 / 127 (1.57%)
    4 / 127 (3.15%)
         occurrences all number
    3
    1
    3
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Oct 2008
    •Investigational site was added & PI was added to Steering Committee •Drug packaging change from blister pack to bottle capsules •Modification of Inclusion and Exclusion Criteria •Modification of lab samples collected •Additional clarifications, deletions and administrative corrections were made throughout the document and Appendices to improve clarity and consistency.
    06 May 2009
    •Modification of Inclusion and Exclusion Criteria •Allowed flexibility with drug dosing time •Modification of lab samples collected •Endpoint Definitions were added •Additional clarifications, deletions and administrative corrections were made throughout the document and Appendices to improve clarity and consistency.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 04 20:33:50 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA