Long-term Safety in Atrial Fibrillation Patients

Study Overview
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Brief Summary
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The purpose of this study is to provide safety and tolerability data for AZD0837 during long-term treatment (5 years) in patients with non-valvular atrial fibrillation (AF) and one or more additional risk factors for stroke and systemic embolic events (moderate to high risk patients).

Official Title
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Long-term Treatment With the Oral Direct Thrombin Inhibitor AZD0837, Compared to Vitamin-K Antagonists, as Stroke Prevention in Patients With Non-valvular Atrial Fibrillation and One or More Risk Factors for Stroke and Systemic Embolic Events. A 5-year Follow-up Study

Conditions
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Persistent or Permanent Nonvalvular Atrial Fibrillation

Intervention / Treatment
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* Drug: AZD0837
* Drug: VKA INR 2-3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with paroxysmal, persistent or permanent Non Valvular Atrial Fibrillation with one or more additional risk factors for stroke and systemic embolic event completing treatment with study drug in D1250C00008. Exclusion Criteria: Atrial Fibrillation secondary to reversible disorders, eg hyperthyroidism Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than Atrial Fibrillation requiring chronic anticoagulation treatment Myocardial infarction, heart surgery or percutaneous coronary intervention (PCI) within the previous three months prior to inclusion; Stroke and/or systemic embolism within the previous 30 days prior to inclusion Conditions associated with increased risk of major bleeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: AZD0837<br>* Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od and then switching to one general common dose, 300 mg od<br>|
| Active Comparator: 2<br> | Drug: VKA INR 2-3<br>* Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5<br>* Other names: warfarin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period | Participants | 154-711 days on treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline | ULN=Upper limit of Normal | From baseline to Follow up | 
| Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline |  | From baseline to Follow up | 
| Creatinine: Absolute Change From Baseline, at End of Treatment |  | Baseline and End of treatment | 
| D-dimer:Median and Quartile Range at End of Treatment | Median (Lower Quartile-Upper Quartile ), ng/mL | End of treatment | 
| Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment | Median Full range, Seconds | Baseline and End of treatment | 
| Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment |  | Baseline and End of Treatment | 
| AZD0837: Plasma Concentration of AZD0837 at End of Treatment |  | End of treatment | 
| AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment |  | 154-711 days on treatment |