Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation

Inclusion Criteria:

• Patients with non-valvular atrial fibrillation who meet all of the following requirements will be considered for admission to the study:

  • Age≧20years
  • Atrial fibrillation confirmed by at least 2 electrocardiographic(ECG) tracings taken at an interval of ≧1week during the year before enrollment

• Presence of any (at least )one of the following risk factors for embolism:

  • Hypertension
  • Diabetes mellitus
  • Congestive heart failure
  • Previous transient ischemic attack (TIA) or cerebral infarction (more than 30 days before giving informed consent )
  • Age≧75 years
  • At time of giving informed consent.
  • To be confirmed on ECG charts, etc.

Exclusion Criteria:

• Presence of any of the following conditions with increased risk of hemorrhage:

  • History of intracranial, intraocular (excluding bleeding beneath the bulbar conjunctiva ), intrathecal, retroperitoneal, or non-traumatic intraarticular hemorrhage
  • History of gastrointestinal hemorrhage during the year before giving informed consent
  • History of peptic ulcers during the 90 days before giving informed consent
  • Surgical treatment or trauma requiring hospitalization during the 30 days before giving informed consent
  • Hemoglobin level <10 g/dL platelet count <10 ×10000 /μL at screening examinations
  • Active hemorrhage* present at giving informed consent or at enrollment
  • Any invasive therapeutic or diagnostic procedure (e.g., surgery, tissue, biopsy, and tooth extraction) scheduled during the period from the time of informed consent until completion of the trial treatment.
  • Any congenital hemorrhagic disease
• History of cerebral infarction or TIA within 30 days before giving informed consent
• Current treatment with any anticoagulant(other than warfarin)
• Concurrent rheumatic valvular disease
• History of valvular surgery
• Concurrent infectious endocarditis
• Concurrent cardiac myxoma
• Confirmed left ventricular or left atrial thrombosis
• Any congenital condition with a tendency toward thrombosis
• Electrical or pharmacological defibrillation scheduled during the trial treatment
• Uncontrolled hypertension (persistently high systolic ［>160mmHg］or diastolic [>100mmHg] pressure)
• Uncontrolled diabetes mellitus

• Renal or hepatic dysfunction (as defined below ), confirmed at screening examinations

  • Serum creatinine>1.5mg/dL
  • AST(GOT)or ALT(GPT)≧twice the upper limit of the reference range
  • Total bilirubin ≧twice the upper limit of the reference range
• Current antiplatelet therapy for any concomitant illness that may be aggravated after discontinuation of the therapy.
• Any concurrent severe cardiac disease
• Known allergy to warfarin or any condition contraindicating its use
• Inability to discontinue current treatment with vitamin K
• Confirmed or potential pregnancy, wish to become pregnant during the study period, or current breast feeding
• Previous treatment with DU-176b
• Participation in a trial of any other drug during the 6 month before giving informed consent
• Any other condition that disqualifies the patient for the study in the opinion of the investigator/subinvestigator *This includes ecchymosis identified as at least one hematoma sized ≧5 cm in longer diameter, macroscopic hematuria, and microscopic hematuria defined as a ≧2+test or a 1+ test for occult blood with a urine sediment containing ≧10 red cells per high-power field (except for a 2+ occult blood test persisting for 1 year before giving informed consent).