Official Title: “A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-Release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety Study

Study Primary Completion Date: June 2008

Intervention(s) in this Clinical Trial

• Drug: AZD0837
  • ER tablet, PO, once daily for a period of 3-9 months.
• Drug: Vitamin-K antagonist at INR 2-3
  • Tablet, PO for a period of 3-9 months.
• Drug: AZD0837
  • ER tablet, PO, twice daily for a period of 3-9 months

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • AZD0837 450 mg
• Experimental: 2
  • AZD0837 200 mg
• Experimental: 3
  • AZD0837 300 mg
• Experimental: 4
  • AZD0837 150 mg
• Active Comparator: 5
  • Vitamin-K antagonist at INR 2-3

Primary Measures

• Safety variables
  • Time Frame: Some of the safety variables will be followed at each visit, some less frequent.
    Safety Issue?: No

Secondary Measures

• Pharmacokinetic parameters
  • Time Frame: Trough PK sampling regularly during the study.
    Safety Issue?: No
• Pharmacodynamic markers
  • Time Frame: Trough PD sampling regularly during the study.
    Safety Issue?: No
• Pharmacogenetics
  • Time Frame: One sampling during the study.
    Safety Issue?: No

Inclusion Criteria:

• Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
• Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
• Previous systemic embolism.
• Symptomatic congestive heart failure (CHF)
• Impaired left ventricular systolic function
• Diabetes mellitus
• Hypertension requiring anti-hypertensive treatment.

Exclusion Criteria:

• AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
• Known contraindication to VKA treatment
• Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
• Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: AstraZeneca

Overall Clinical Trial Officials and Contacts

Gregory Y Lip, Prof Principal Investigator University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00684307

Study ID Number: D1250C00008

ClinicalTrials.gov Identifier: NCT00684307

Health Authority: Austria: Agency for Health and Food Safety