Atrial Fibrillation (AF) Patients Not Taking Vitamin-K Antagonist (VKA)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of AZD0837 in patients with atrial fibrillation who are unable or unwilling to take vitamin K antagonist therapy for up to 3 months.

Official Title
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A Controlled, Randomized, Parallel , Multi-centre Feasibility Study of the Oral Direct Thrombin Inhibitor, AZD0837, Given as ER Formulation, in the Prevention of Stroke and Systolic Embolic Events in Patients With Atrial Fibrillation, Who Are Appropriate for But Unable/Unwilling to Take VKA Therapy

Conditions
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Persistent or Permanent Non-valvular Atrial Fibrillation

Intervention / Treatment
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* Drug: AZD0837
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either one of the following risk factors is sufficient for inclusion (high risk patient) Previous cerebral ischaemic attack (stroke or transient ischaemic attack (TIA), >30 days prior to randomization) Previous systemic embolism or at least one of the following risk factors are needed for inclusion: Age ≥75 years Symptomatic congestive heart failure Impaired left ventricular systolic function Diabetes mellitus; Hypertension requiring anti-hypertensive treatment In addition to AF the patient must be appropriate for but unable or unwilling to take VKA therapy Exclusion Criteria: Presence of a clinically significant valvular heart disease;; Stroke or TIA and/or systemic embolism within the previous 30 days prior to randomization 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AZD0837|ER formulation|
|Drug: Aspirin|Oral form|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Premature Discontinuation of Study or Study Drug Due to Any Reason | The premature discontinuation of study or study drug due to any reason | 28 week (randomisation visit to last follow up visit in study) according to protocols | 
| Premature Discontinuation of Study Drug Due to Any Reason | The premature discontinuation of study drug due to any reason | 24 weeks (randomisation visit to last treatment visit) | 
| Premature Discontinuation of Study Due to Any Reason | |The premature discontinuation of study due to any reason | 28 weeks (randomisation visit to last follow up visit) | 
| Compliance With Study Drug | [(number of doses dispensed-number of doses returned)/number of days between visits]*100 | 24 weeks (randomisation visit to last treatment visit) according to protocol | 
| Compliance With Study Visits/Assessments | (number of visits attended acroos the time of study divided by the number of expected visits according to the time of entry into study)*100 | 28 weeks (randomisation visit to last follow up visit) according to protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Events | Number of patients with a bleeding event while on study drug. Patients with multiple bleeding events are counted once | 24 weeks (randomisation visit to last treatment visit) according to protocol. For patients who discontinued treatment the time frame was <24 weeks. Mean number of weeks was 7 weeks (baseline to end of treatment visit) | 
| Change in Creatinine Level | Individual change in Creatinine level (umil/L) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline) | 4 weeks according to protocol (randomisation visit to week 4 visit) | 
| Alanine Aminotransferase (ALAT) | Number of patients while on study drug with Alanine aminotransferase (ALAT)>=3 times upper limit of normal. | 24 weeks (randomisation visit to last treatment visit) according to protocol. For patients who discontinued treatment the time frame was <24 weeks. Mean number of weeks was 7 weeks (baseline to end of treatment visit) | 
| Bilirubin | Number of patients while on study drug with Bilirubin>=2 times upper limit of normal. | 24 weeks (randomisation visit to last treatment visit) according to protocol. For patients who discontinued treatment the time frame was <24 weeks. Mean number of weeks was 7 weeks (baseline to end of treatment visit) | 
| Plasma Concentration of AZD0837 (Prodrug) | Assessment of plasma concentration of AZD0837 (prodrug) made on the week 4 visit | 4 weeks after baseline according to protocol | 
| Plasma Concentration of AR-H067637XX (Active Metabolite) | Assessment of plasma concentration of AR-H067637XX (active metabolite) made on the week 4 visit | 4 weeks after baseline according to protocol | 
| Change in D-Dimer Level | Individual change in D-Dimer level (ng/ml) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline) | 4 weeks according to protocol.(baseline to week 4 visit) | 
| Activated Partial Thromboplastin Time (APTT) | Individual change in Activated partial thromboplastin time (APTT) (sec) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline) | 4 weeks according to protocol.(baseline to week 4 visit) | 
| Ecarin Clotting Time (ECT) | Individual change in Ecarin clotting time (ECT) (sec) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline) | 4 weeks according to protocol.(baseline to week 4 visit) |