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

NCT00742859 | Completed Phase 2 Results DMC

• 1 other identifier: 08-015
• Study Type: interventional
• Target: 508
• Locations: 2 countries
• Sites: 21

Brief Summary

Prevention of stroke in patients with atrial fibrillation (AF). Hypothesis: In patients with non-valvular AF, orally administered betrixaban will provide similar or better efficacy and safety than warfarin and it will offer the advantage of not requiring dose adjustments due to international normalized ratios (INRs) outside the target range of 2.0 to 3.0 and a more consistent level of anticoagulation over time.

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation; Betrixaban; Factor Xa inhibitor; Warfarin

Outcome Measures

Primary Outcomes (1)

• Exposure-adjusted Incidence Rate of Major or Clinically Relevant Non-major Bleeding Episode

  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.

  A maximum of 1 year

Secondary Outcomes (1)

• Exposure-adjusted Incidence Rate of Any Bleeding (Major, Clinically Relevant Non-major, or Minimal)

  A maximum of 1 year

Study Arms (4)

Arm 1: Betrixaban

EXPERIMENTAL

Betrixaban, 40 mg, orally, once daily for at least 3 months.

Drug: betrixaban

Arm 2: Betrixaban

EXPERIMENTAL

Betrixaban, 60 mg, orally, once daily for at least 3 months

Drug: betrixaban

Arm 3: Betrixaban

EXPERIMENTAL

Betrixaban, 80 mg, orally, once daily for at least 3 months

Drug: betrixaban

Arm 4: Warfarin

ACTIVE COMPARATOR

Warfarin will be prescribed by investigators according to the standard of care.

Drug: Warfarin

Interventions

betrixaban DRUG

orally, once daily for at least 3 months

Arm 1: Betrixaban; Arm 2: Betrixaban; Arm 3: Betrixaban

Warfarin DRUG

Warfarin will be prescribed by the investigator according to the standard of care.

Also known as: Coumadin, Acenocoumarol

Arm 4: Warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥18 years.
• If the patient is a woman, she must be without reproductive potential (i.e., postmenopausal for ≥2 years or after hysterectomy).
• AF at the time of enrollment (randomization) or documented within the last year by Holter, ECG, rhythm strip, pacemaker or other intracardiac recording, resulting in an indication for anticoagulation with warfarin, acenocumerol, phenprocoumon, or other Vitamin K antagonist in the opinion of the treating physician.
• One or more of the following risk factor(s) for stroke:
• Age 75 years or older.
• Prior stroke, TIA or systemic (i.e., central nervous system) embolus at least 30 days remote from the time of screening.
• Symptomatic congestive heart failure within 3 months echocardiography, radionuclide study or contrast angiography.
• Hypertension requiring pharmacological treatment.
• Diabetes.
• Age of 55 years or older and previous coronary artery disease or known peripheral artery disease.

You may not qualify if:

• Body weight less than 40 kg (88 lbs).
• Need for either hemodialysis or peritoneal dialysis (or likely to require it within one year).
• AF due to reversible causes (e.g., thyrotoxicosis, pericarditis, cardiac surgery, pulmonary embolism).
• Mechanical prosthetic valve (bioprosthetic valve is allowed) or valvular disease likely to be operated on within one year.
• History (including family history) or symptoms of a congenital or acquired bleeding disorder or vascular malformation; or a history of intracranial, retroperitoneal, or intraocular bleeding within the last 6 months; or is felt to be at high risk for bleeding for other reasons including from significant liver disease. This also includes gastrointestinal bleeding within 90 days before randomization or endoscopically verified ulcer disease within 30 days of screening.
• Conditions other than AF that require chronic anticoagulation (e.g. prosthetic mechanical heart valve).
• Persistent, uncontrolled hypertension (SBP \>160 mm Hg on repeated measurements).
• Active infective endocarditis.
• Scheduled major surgery.
• Planned pulmonary vein ablation or surgical procedure for cure of AF or flutter.
• Recent ischemic stroke, systemic embolic event or acute coronary syndrome within 30 days.
• Severe co-morbid condition with life expectancy of ≤1 year.
• Previous known history of genetic coagulopathy (e.g., Factor V Leiden, Protein C Deficiency, Protein S Deficiency, Antiphospholipid Syndrome, etc.).
• Evidence at Screening of:
• Platelet count \<100,000/mm3.

Sponsors & Collaborators

• Portola Pharmaceuticals: lead

Study Sites (21)

Portola Investigational Site

Anaheim, California, 92801, United States

Location

Portola Investigational Site

Colorado Springs, Colorado, 80909, United States

Location

Portola Investigational Site

Melbourne, Florida, 32901, United States

Location

Portola Investigational Site

Miami, Florida, 33173, United States

Location

Portola Investigational Site

Ormond Beach, Florida, 32174, United States

Location

Portola Investigational Site

Pensacola, Florida, 32501, United States

Location

Portola Investigational Site

Port Charlotte, Florida, 33952, United States

Location

Portola Investigational Site

Aurora, Illinois, 60504, United States

Location

Portola Investigational Site

Auburn, Maine, 04210, United States

Location

Portola Investigational Site

Columbia, Maryland, 21044, United States

Location

Portola Investigational Site

Salisbury, Maryland, 21804, United States

Location

Portola Investigational Site

Towson, Maryland, 21204, United States

Location

Portola Investigational Site

Tupelo, Mississippi, 38801, United States

Location

Portola Investigational Site

St Louis, Missouri, 63110, United States

Location

Portola Investigational Site

Poughkeepsie, New York, 12601, United States

Location

Portola Investigational Site

Hillsboro, Oregon, 97123, United States

Location

Portola Investigational Site

Wynnewood, Pennsylvania, 19096, United States

Location

Portola Investigational Site

Rapid City, South Dakota, 57701, United States

Location

Portola Investigational Site

Norfolk, Virginia, 23507, United States

Location

Portola Investigational Site

Longueuil, Quebec, Canada

Location

Portola Investigational Site

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

betrixaban; Warfarin; Acenocoumarol

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Portola Pharmaceuticals, Inc.

650-246-7000

Study Officials

• Stuart Connolly, MD, FRCP

  Population Health Research Institute, McMaster University

  STUDY CHAIR

• Rafael Diaz, MD

  Instituto Cardiovascular de Rosario, Argentina

  STUDY DIRECTOR

• Paul Dorian, MD

  University of Toronto, Canada

  STUDY DIRECTOR

• Michael Ezekowitz, MD, PhD,

  Lankenau Institute for Medical Research and The Heart Center, United States

  STUDY DIRECTOR

• Stefan H. Hohnloser, MD

  Johann Wolgang Goethe University, Frankfurt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 28, 2008
• Study Start: October 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: November 1, 2009
• Last Updated: August 7, 2023
• Results First Posted: September 26, 2017

Record last verified: 2023-08

Locations

US (19); CA (2)