Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: DU-176b tablets; Warfarin potassium tablets
Intervention description: DU-176b tablets taken once daily for up to 12 weeks; Warfarin potassium tablets taken once daily for up to 12 weeks
Intervention MeSH terms: Warfarin; Edoxaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 536.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Atrial fibrillation; Factor Xa inhibition

Summary:

      The primary objective of this study is to compare the incidence of hemorrhagic events in
      patients treated for non-valvular atrial fibrillation with DU-176b at each dose level versus
      warfarin potassium (warfarin). The secondary objective includes between-group comparisons
      with regard to incidence of thromboembolic events, pharmacodynamic parameters, and biomarkers
      for the efficacy evaluation, as well as incidence of adverse events and adverse reaction for
      the safety evaluation.
    

Eligibility criteria:

        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).