Official Title: “A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of DU-176b Versus Warfarin In Subjects With Atrial Fibrillation - Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE - AF TIMI 48)”

This study is to demonstrate the safety and efficacy profile, in two different dose regimens of DU-176b, (an investigational new drug being tested for the prevention of stroke/systemic embolic events (SEE)), in individuals with atrial fibrillation. Patients will be randomized to one of three treatment groups: High Dose Regimen, Low Dose Regimen, & Warfarin. The expected duration of the study is 24 months.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2011

Intervention(s) in this Clinical Trial

• Drug: warfarin tablets
  • Warfarin tablets plus DU-176b placebo tablets each taken once daily for 24 months
• Drug: DU-176b tablets (high dose regimen)
  • DU-176b tablets plus warfarin placebo tablets each taken once daily for 24 months
• Drug: DU-176b tablets (low dose regimen)
  • DU-176b tablets plus warfarin placebo tablets each taken once daily for 24 months

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Warfarin tablets plus placebo DU-176b tablets
• Experimental: 2
  • DU-176b tablets plus warfarin placebo tablets
• Experimental: 3
  • DU-176b tablets plus warfarin placebo tablets

Primary Measures

• The primary objective is to compare DU-176b to warfarin with regard to the composite primary endpoint of stroke and systemic embolic events.
  • Time Frame: 24 Months
    Safety Issue?: No

Secondary Measures

• To compare DU-176b to warfarin with regard to the composite clinical outcome of stroke, SEE, and all-cause mortality
  • Time Frame: 24 Months
    Safety Issue?: No
• To compare DU-176b to warfarin with regard to major bleeding events
  • Time Frame: 24 Months
    Safety Issue?: Yes

Inclusion Criteria:

• 21 years of age or older; male or female.
• Able to provide written informed consent.
• History of documented AF within the prior 12 months
• A moderate to high risk of stroke, as defined by CHADS2 index score of at least 2

Exclusion Criteria:

• Transient atrial fibrillation secondary to other reversible disorders
• Subjects with moderate or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve
• Subjects with any contraindication for anticoagulant agents;
• Subjects with conditions associated with high risk of bleeding or have known or suspected hereditary or acquired bleeding disorders
• Females of childbearing potential including the following:
• Females with a history of tubal-ligation
• Females less than 2 years post-menopausal

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Daiichi Sankyo Inc.

Overall Clinical Trial Officials and Contacts

Overall Contact: Shirali Patel 919-998-1452 shirali.patel@quintiles.com

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00781391

Study ID Number: DU176b-C-U301

ClinicalTrials.gov Identifier: NCT00781391

Health Authority: United States: Food and Drug Administration