Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation

Completed

Phase 2 Results

Trial Description

The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.

Conditions

Interventions

  • Warfarin (Coumadin®)Drug
    Intervention Desc: Anticoagulant (Vitamin K antagonist)
  • AZD0837 (Exanta )Drug
    Intervention Desc: ER tablet, PO, twice daily for a period of 3-9 months
    ARM 1: Kind: Experimental
    Label: 1
    Description: AZD0837 450 mg
    ARM 2: Kind: Experimental
    Label: 3
    Description: AZD0837 300 mg
    ARM 3: Kind: Experimental
    Label: 4
    Description: AZD0837 150 mg
    ARM 4: Kind: Experimental
    Label: 2
    Description: AZD0837 200 mg
  • Vitamin-K antagonist at INR 2-3 Drug
    Other Names: Warfarin
    Intervention Desc: Tablet, PO for a period of 3-9 months.
    ARM 1: Kind: Experimental
    Label: 5
    Description: Vitamin-K antagonist at INR 2-3

Trial Design

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

Patient Involvement

Patient will be randomized to one of 4 doses of AZD0837 or vitamin K antagonist and will have regular blood tests to determine safety variables, pharmacokinetic parameters, pharmacodynamic markers and pharmacogenetics. Follow-up will be 3 to 9 months.

Outcomes

Type Measure Time Frame Safety Issue
Primary Safety variables
Secondary Pharmacokinetic parameters; pharmacodynamic markers; pharmacogenetics.
Secondary Pharmacokinetic parameters Trough PK sampling regularly during the study. No
Secondary Pharmacodynamic markers Trough PD sampling regularly during the study. No
Secondary Pharmacogenetics One sampling during the study. No
Primary Bleeding Events 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit) Yes
Primary Creatinine 12 weeks according to protocol.(baseline to week 12 visit)  Yes
Primary Alanine Aminotransferase (ALAT) 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)  Yes
Primary Bilirubin 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit) Yes
Secondary D-Dimer 14 weeks according to protocol.(enrolment to week 12 visit)  Yes
Secondary Activated Partial Thromboplastin Time (APTT) 12 weeks according to protocol.(baseline to week 12 visit)  Yes
Secondary Ecarin Clotting Time (ECT) 12 weeks according to protocol.(baseline to week 12 visit)  Yes
Secondary Plasma Concentration of AZD0837 (Prodrug) 12 weeks after baseline according to protocol No
Secondary Plasma Concentration of AR-H067637XX (Active Metabolite) 12 weeks after baseline according to protocol No
Secondary Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT 36 weeks according to protocol No
Secondary Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC 36 weeks according to protocol No
Secondary Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC 36 weeks according to protocol No

Sponsors