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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00829933
Recruitment Status : Completed
First Posted : January 27, 2009
Results First Posted : January 26, 2015
Last Update Posted : January 9, 2019
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Brief 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.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: DU-176b tablets Drug: Warfarin potassium tablets Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 536 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized Dose-ranging Controlled Trial of DU-176b Versus Warfarin Potassium in Patients With Non-valvular Atrial Fibrillation
Study Start Date : March 2007
Actual Primary Completion Date : July 2008
Actual Study Completion Date : September 2008

Arm Intervention/treatment
Experimental: 1
DU-176b low dose
Drug: DU-176b tablets
DU-176b tablets taken once daily for up to 12 weeks

Experimental: 2
DU-176b intermediate dose
Drug: DU-176b tablets
DU-176b tablets taken once daily for up to 12 weeks

Experimental: 3
DU-176b high dose
Drug: DU-176b tablets
DU-176b tablets taken once daily for up to 12 weeks

Active Comparator: 4
Drug: Warfarin potassium tablets
Warfarin potassium tablets taken once daily for up to 12 weeks

Primary Outcome Measures :
  1. Incidence of Bleeding Events (Major Bleeding, Clinically Relevant Non-major Bleeding and Minor Bleeding ) Identified During the Period From the Entry Into the Treatment Period Until Completion or Termination of the Treatment. [ Time Frame: 12 weeks ]
    The primary endpoint was the incidence of bleeding events (major bleeding, clinically relevant non-major bleeding, or minor bleeding) that occurred during the treatment period.

Secondary Outcome Measures :
  1. Incidence of Thromboembolic Events (Cerebral Infarction and Systemic Embolism) Identified During the Period From the Entry to the Treatment Period Until Completion or Termination of the Treatment. [ Time Frame: 12 weeks ]
  2. Incidence of Adverse Events and Adverse Reactions Identified During the Period From the Entry to the Treatment Period Until Completion or Termination of the Treatment [ Time Frame: 12 weeks ]
  3. Pharmacodynamic Parameters (PT, PT-INR, and APTT) [ Time Frame: 12 weeks ]
    PT - prothrombin time INR - International Normalized Ratio APTT - Activated Partial Thromboplastin time

  4. Plasma DU-176 Concentration [ Time Frame: 12 weeks ]
  5. Pharmacodynamic Biomarkers (F1+2, TAT, and D-dimer ) [ Time Frame: 12 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00829933

Tokyo, Japan
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.

Responsible Party: Daiichi Sankyo Co., Ltd. Identifier: NCT00829933     History of Changes
Other Study ID Numbers: DU176b-C-J225
First Posted: January 27, 2009    Key Record Dates
Results First Posted: January 26, 2015
Last Update Posted: January 9, 2019
Last Verified: February 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address:
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Atrial fibrillation
Factor Xa inhibition

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action