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

Completed

Phase 2 Results

Trial Description

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.

Detailed Description

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 dose-adjusted warfarin in patients with non-valvular atrial fibrillation (AF).
This is a Phase 2, exploratory, randomized, parallel group, multicenter, active comparator, dose finding study of patients with documented non-valvular AF. Patients will be randomized (1:1:1:1) to 1 of 4 treatment groups (approximately 125 patients per group) using an interactive voice response system (IVRS). A dynamic randomization will be used to balance patients by country, concurrent aspirin use (yes or no) and antecedent warfarin (yes or no). The study will be open label for randomization to warfarin versus betrixaban, but the three daily doses of betrixaban, 40 mg, 60 mg or 80 mg, will be double-blind (identical capsules for all three dose levels). The warfarin-treated patients will be managed according to each center's usual clinical routine with INR monitoring and dose-adjustments in order to maintain a target INR of 2.0 to 3.0 at maximum intervals of four weeks. No loading doses or dose titrations will be used for betrixaban. The betrixaban dose should be ingested in the evening (e.g. at bedtime), preferably at least 2 hours after the evening meal. Note: acenocumerol may be substituted for warfarin as indicated by local practice.

Conditions

Interventions

  • Warfarin (Coumadin┬«)Drug
    Other Names: Coumadin; Acenocoumarol
    Intervention Desc: Warfarin will be prescribed by the investigator according to the standard of care.
    ARM 1: Kind: Experimental
    Label: Arm 4: Warfarin
    Description: Warfarin will be prescribed by investigators according to the standard of care.
  • Betrixaban Drug
    Intervention Desc: orally, once daily for at least 3 months
    ARM 1: Kind: Experimental
    Label: Arm 1: Betrixaban
    Description: Betrixaban, 40 mg, orally, once daily for at least 3 months.
    ARM 2: Kind: Experimental
    Label: Arm 2: Betrixaban
    Description: Betrixaban, 60 mg, orally, once daily for at least 3 months
    ARM 3: Kind: Experimental
    Label: Arm 3: Betrixaban
    Description: Betrixaban, 80 mg, orally, once daily for at least 3 months

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized (1:1:1:1) to 1 of 4 treatment groups (approximately 125 patients per group) using an IVRS. A dynamic randomization will be used to balance patients by country, concurrent aspirin use (yes or no) and antecedent warfarin (yes or no). The study will be open label for randomization to warfarin versus betrixaban, but the three daily doses of betrixaban, 40 mg, 60 mg or 80 mg, will be double-blind (identical capsules for all three dose levels). The warfarin-treated patients will be managed according to each center's usual clinical routine with INR monitoring and dose-adjustments in order to maintain a target INR of 2.0 to 3.0 at maximum intervals of four weeks. No loading doses or dose titrations will be used for betrixaban. Treatment will be for 90 days.

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary endpoint will be the occurrence of major or clinically relevant non-major bleeding.
Primary Exposure-adjusted Incidence Rate of Major or Clinically Relevant Non-major Bleeding Episode A maximum of 1 year
Secondary Exposure-adjusted Incidence Rate of Any Bleeding (Major, Clinically Relevant Non-major, or Minimal) A maximum of 1 year

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