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.
Name: AZD0837
Description: ER tablet, PO, once daily for a period of 3-9 months.Type: Drug1 3 4
Name: Vitamin-K antagonist at INR 2-3
Description: Tablet, PO for a period of 3-9 months.Type: Drug5
Name: AZD0837
Description: ER tablet, PO, twice daily for a period of 3-9 monthsType: Drug2
Description: Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once
Measure: Bleeding Events Time: 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)Description: Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Measure: Creatinine Time: 12 weeks according to protocol.(baseline to week 12 visit)Description: Number of patients while on study drug with ALAT>=3 times upper limit of normal.l
Measure: Alanine Aminotransferase (ALAT) Time: 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)Description: Number of patients while on study drug with Bilirubin>=2 times upper limit of normal
Measure: Bilirubin Time: 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)Description: Change in D-Dimer values from enrolment to week 12 visit for VKA naïve patients while on study drug (week 12 visit-enrolment)
Measure: D-Dimer Time: 14 weeks according to protocol.(enrolment to week 12 visit)Description: Change in Activated partial thromboplastin time (APTT) from baseline to week 12 visit for VKA naïve patients while on study drug (week 12 visit-baseline)
Measure: Activated Partial Thromboplastin Time (APTT) Time: 12 weeks according to protocol.(baseline to week 12 visit)Description: Change in Ecarin clotting time (ECT) from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Measure: Ecarin Clotting Time (ECT) Time: 12 weeks according to protocol.(baseline to week 12 visit)Description: Assessment made on the week 12 visit
Measure: Plasma Concentration of AZD0837 (Prodrug) Time: 12 weeks after baseline according to protocolDescription: Assessment made on the week 12 visit
Measure: Plasma Concentration of AR-H067637XX (Active Metabolite) Time: 12 weeks after baseline according to protocolDescription: Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T
Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT Time: 36 weeks according to protocolDescription: Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T
Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC Time: 36 weeks according to protocolDescription: Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T
Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC Time: 36 weeks according to protocolAllocation: Randomized
Parallel Assignment
There is one SNP
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT. --- C3435T ---
Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T. --- C3435T ---
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC. --- C3435T ---
Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T. --- C3435T ---
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC. --- C3435T ---
Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T. --- C3435T ---