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Trial record 61 of 230 for:    warfarin AND International

Phase 2 Study of the Safety, Tolerability and Pilot Efficacy of Oral Factor Xa Inhibitor Betrixaban Compared to Warfarin (EXPLORE-Xa)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00742859
Recruitment Status : Completed
First Posted : August 28, 2008
Results First Posted : September 26, 2017
Last Update Posted : October 26, 2017
Sponsor:
Information provided by (Responsible Party):
Portola Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Atrial Fibrillation
Interventions Drug: betrixaban
Drug: Warfarin
Enrollment 508
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 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.
Arm/Group Title Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Hide Arm/Group Description Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months 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
Period Title: Overall Study
Started 127 127 127 127
Completed 116 115 116 119
Not Completed 11 12 11 8
Reason Not Completed
Adverse Event             5             6             3             1
Death             1             0             0             1
Physician Decision             1             2             0             0
Withdrawal by Subject             4             2             4             1
Endpoint             0             1             1             2
Amendment 2 patient off study drug >4wks             0             1             1             0
Sponsor req visit schedule noncompliance             0             0             0             1
Sponsor request patient out of town             0             0             1             1
Site error             0             0             1             1
Arm/Group Title Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin Total
Hide Arm/Group Description Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months 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 Total of all reporting groups
Overall Number of Baseline Participants 127 127 127 127 508
Hide Baseline Analysis Population Description
All randomized patients who took at least 1 dose of study medication after randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 127 participants 127 participants 127 participants 127 participants 508 participants
73.3  (8.50) 73.8  (8.35) 72.0  (7.65) 72.7  (8.75) 73.0  (8.32)
Age, Customized  
Measure Type: Number
Unit of measure:  Count of Participants
Number Analyzed 127 participants 127 participants 127 participants 127 participants 508 participants
<75 years 64 61 76 67 268
>=75 years 63 66 51 60 240
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 127 participants 127 participants 127 participants 127 participants 508 participants
Female
48
  37.8%
46
  36.2%
38
  29.9%
38
  29.9%
170
  33.5%
Male
79
  62.2%
81
  63.8%
89
  70.1%
89
  70.1%
338
  66.5%
1.Primary Outcome
Title Exposure-adjusted Incidence Rate of Major or Clinically Relevant Non-major Bleeding Episode
Hide 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.
Time Frame A maximum of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who took at least 1 dose of study medication after randomization.
Arm/Group Title Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Hide Arm/Group Description:
Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months
Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months
Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months
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
Overall Number of Participants Analyzed 127 127 127 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of Patients per 100 Patient years
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Betrixaban 40 mg, Warfarin
Comments Betrixaban 40mg compared to Warfarin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.017 to 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Betrixaban 60 mg, Warfarin
Comments Betrixaban 60mg compared to Warfarin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.546
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.711
Confidence Interval (2-Sided) 95%
0.225 to 2.24
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Betrixaban 80 mg, Warfarin
Comments Betrixaban 80mg compared to Warfarin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.712
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.755
Confidence Interval (2-Sided) 95%
0.239 to 2.39
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Exposure-adjusted Incidence Rate of Any Bleeding (Major, Clinically Relevant Non-major, or Minimal)
Hide 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.
Time Frame A maximum of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who took at least 1 dose of study medication after randomization.
Arm/Group Title Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Hide Arm/Group Description:
Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months
Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months
Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months
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
Overall Number of Participants Analyzed 127 127 127 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of Patients per 100 Patient years
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Betrixaban 40 mg, Warfarin
Comments Betrixaban 40mg compared to Warfarin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.508
Confidence Interval (2-Sided) 95%
0.301 to 0.856
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Betrixaban 60 mg, Warfarin
Comments Betrixaban 60mg compared to Warfarin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.308
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.767
Confidence Interval (2-Sided) 95%
0.481 to 1.22
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Betrixaban 80 mg, Warfarin
Comments Betrixaban 80mg compared to Warfarin
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.551
Confidence Interval (2-Sided) 95%
0.332 to 0.914
Estimation Comments [Not Specified]
Time Frame Maximum of 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Hide Arm/Group Description Betrixaban 40 mg once daily for at least 3 months and no longer than approximately 11 months Betrixaban 60 mg once daily for at least 3 months and no longer than approximately 11 months Betrixaban 80 mg once daily for at least 3 months and no longer than approximately 11 months 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
All-Cause Mortality
Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   61/127 (48.03%)   68/127 (53.54%)   53/127 (41.73%)   50/127 (39.37%) 
Show Serious Adverse Events Hide Serious Adverse Events
Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/127 (9.45%)   12/127 (9.45%)   11/127 (8.66%)   12/127 (9.45%) 
Blood and lymphatic system disorders         
Anaemia   1/127 (0.79%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Thrombocytopenia   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Cardiac disorders         
Cardiac failure congestive   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  3/127 (2.36%) 
Atrial Fibrillation   1/127 (0.79%)  1/127 (0.79%)  1/127 (0.79%)  0/127 (0.00%) 
Ventricular Tachycardia   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Angina Unstable   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Coronary Artery Disease   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Sick Sinus Syndrome   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Endocrine disorders         
Inappropriate Antidiuretic Hormone Secretion   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Gastrointestinal disorders         
Abdominal Hernia Obstructive   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Abdominal Pain Upper   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Nausea   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
General disorders         
Chest Pain   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Non-Cardiac Chest Pain   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Infections and infestations         
Cellulitis   1/127 (0.79%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Cystitis   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  1/127 (0.79%) 
Urinary Tract Infection   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Pneumonia   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Pyelonephritis   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Injury, poisoning and procedural complications         
Fall   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Investigations         
Internaional Normalised Ratio Increased   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Metabolism and nutrition disorders         
Anorexia   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Diabetes Mellitus Inadequate Control   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Fluid Overload   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Gout   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Hypoglycaemia   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back Pain   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Ligament Disorder   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Muscular Weakness   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast Cancer   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Cardiac Neoplasm Unspecified   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Chronic Lymphocytic Leukaemia   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Colon Cancer Recurrent   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Lung Neoplasm Malignant   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Renal Cancer   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Nervous system disorders         
Grand Mal Convulsion   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Lumbar Radiculopathy   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Presyncope   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Syncope   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Psychiatric disorders         
Hallucination   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Reproductive system and breast disorders         
Prostatic Obstruction   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Chronic Obstructive Pulmonary Disease   1/127 (0.79%)  1/127 (0.79%)  1/127 (0.79%)  0/127 (0.00%) 
Asthma   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Pleural Effusion   1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%) 
Vascular disorders         
Arterial Stenosis   0/127 (0.00%)  0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%) 
Deep Vein Thrombosis   0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%)  0/127 (0.00%) 
Hypotension   0/127 (0.00%)  0/127 (0.00%)  1/127 (0.79%)  0/127 (0.00%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Betrixaban 40 mg Betrixaban 60 mg Betrixaban 80 mg Warfarin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   61/127 (48.03%)   68/127 (53.54%)   53/127 (41.73%)   50/127 (39.37%) 
Cardiac disorders         
ATRIAL FIBRILLATION   1/127 (0.79%)  0/127 (0.00%)  1/127 (0.79%)  4/127 (3.15%) 
Gastrointestinal disorders         
NAUSEA   2/127 (1.57%)  5/127 (3.94%)  14/127 (11.02%)  2/127 (1.57%) 
DIARRHOEA   4/127 (3.15%)  10/127 (7.87%)  9/127 (7.09%)  1/127 (0.79%) 
VOMITING   1/127 (0.79%)  2/127 (1.57%)  6/127 (4.72%)  1/127 (0.79%) 
DYSPEPSIA   7/127 (5.51%)  0/127 (0.00%)  4/127 (3.15%)  1/127 (0.79%) 
CONSTIPATION   9/127 (7.09%)  8/127 (6.30%)  3/127 (2.36%)  3/127 (2.36%) 
ABDOMINAL PAIN   2/127 (1.57%)  5/127 (3.94%)  2/127 (1.57%)  1/127 (0.79%) 
General disorders         
OEDEMA PERIPHERAL   8/127 (6.30%)  10/127 (7.87%)  6/127 (4.72%)  11/127 (8.66%) 
FATIGUE   7/127 (5.51%)  5/127 (3.94%)  4/127 (3.15%)  4/127 (3.15%) 
CHEST PAIN   5/127 (3.94%)  1/127 (0.79%)  2/127 (1.57%)  3/127 (2.36%) 
Infections and infestations         
BRONCHITIS   1/127 (0.79%)  2/127 (1.57%)  4/127 (3.15%)  0/127 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION   5/127 (3.94%)  1/127 (0.79%)  4/127 (3.15%)  3/127 (2.36%) 
INFLUENZA   2/127 (1.57%)  1/127 (0.79%)  4/127 (3.15%)  1/127 (0.79%) 
NASOPHARYNGITIS   5/127 (3.94%)  5/127 (3.94%)  3/127 (2.36%)  10/127 (7.87%) 
URINARY TRACT INFECTION   3/127 (2.36%)  1/127 (0.79%)  2/127 (1.57%)  4/127 (3.15%) 
Investigations         
LIVER FUNCTION TEST ABNORMAL   1/127 (0.79%)  4/127 (3.15%)  0/127 (0.00%)  3/127 (2.36%) 
Musculoskeletal and connective tissue disorders         
BACK PAIN   5/127 (3.94%)  6/127 (4.72%)  6/127 (4.72%)  2/127 (1.57%) 
ARTHRALGIA   3/127 (2.36%)  6/127 (4.72%)  3/127 (2.36%)  4/127 (3.15%) 
Nervous system disorders         
HEADACHE   5/127 (3.94%)  6/127 (4.72%)  9/127 (7.09%)  3/127 (2.36%) 
DIZZINESS   12/127 (9.45%)  9/127 (7.09%)  6/127 (4.72%)  3/127 (2.36%) 
Psychiatric disorders         
INSOMNIA   2/127 (1.57%)  4/127 (3.15%)  5/127 (3.94%)  0/127 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
DYSPNOEA   4/127 (3.15%)  3/127 (2.36%)  5/127 (3.94%)  2/127 (1.57%) 
COUGH   3/127 (2.36%)  8/127 (6.30%)  3/127 (2.36%)  3/127 (2.36%) 
Skin and subcutaneous tissue disorders         
RASH   4/127 (3.15%)  3/127 (2.36%)  3/127 (2.36%)  1/127 (0.79%) 
Vascular disorders         
HYPERTENSION   3/127 (2.36%)  3/127 (2.36%)  1/127 (0.79%)  4/127 (3.15%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Due to multiple studies, centers and countries this may vary.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Clinical Development
Organization: Portola Pharmaceuticals, Inc.
Phone: 650-246-7000
Layout table for additonal information
Responsible Party: Portola Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00742859     History of Changes
Other Study ID Numbers: 08-015
First Submitted: August 26, 2008
First Posted: August 28, 2008
Results First Submitted: July 20, 2017
Results First Posted: September 26, 2017
Last Update Posted: October 26, 2017