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

Sponsored by:	Daiichi Sankyo Co., Ltd.
Information provided by:	Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:	NCT00829933

Purpose

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	Intervention	Phase
Atrial Fibrillation	Drug: DU-176b tablets Drug: Warfarin potassium tablets	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized Dose-Ranging Controlled Trial of DU-176b Versus Warfarin Potassium in Patients With Non-Valvular Atrial Fibrillation

Resource links provided by NLM:

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Atrial Fibrillation Blood Thinners

Drug Information available for: Warfarin Warfarin sodium Warfarin potassium Potassium chloride

U.S. FDA Resources

Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:

Incidence of hemorrhagic events (major bleeding, clinically relevant non-major bleeding and minor bleeding ) identified during the period from the entry to the treatment period until completion or termination of the treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
Pharmacodynamic parameters (PT, PT-INR, and APTT) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Plasma DU-176 concentration [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Pharmacodynamic biomarkers (F1+2, TAT, and D-dimer ) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	536
Study Start Date:	March 2007
Study Completion Date:	September 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental DU-176b low dose	Drug: DU-176b tablets DU-176b tablets taken once daily for up to 12 weeks
2: Experimental DU-176b intermediate dose	Drug: DU-176b tablets DU-176b tablets taken once daily for up to 12 weeks
3: Experimental DU-176b high dose	Drug: DU-176b tablets DU-176b tablets taken once daily for up to 12 weeks
4: Active Comparator Warfarin	Drug: Warfarin potassium tablets Warfarin potassium tablets taken once daily for up to 12 weeks

Eligibility

Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829933

Locations

Japan

Tokyo, Japan

Sponsors and Collaborators

Daiichi Sankyo Co., Ltd.

More Information

No publications provided

Responsible Party:	Daiichi Sankyo Co., Ltd. ( Clinical Development Department III, Group II )
Study ID Numbers:	DU176b-C-J225
Study First Received:	January 26, 2009
Last Updated:	January 26, 2009
ClinicalTrials.gov Identifier:	NCT00829933 History of Changes
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Daiichi Sankyo Inc.:

Atrial fibrillation
Factor Xa inhibition

Study placed in the following topic categories:

Anticoagulants
Heart Diseases
Warfarin
Atrial Fibrillation
Arrhythmias, Cardiac

Additional relevant MeSH terms:

Anticoagulants
Pathologic Processes
Heart Diseases
Therapeutic Uses
Hematologic Agents

Cardiovascular Diseases
Warfarin
Atrial Fibrillation
Pharmacologic Actions
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on September 10, 2009