Back to resultsA Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation
Primary Purpose
Atrial Fibrillation, Thromboembolism
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Edoxaban (DU-176b)
Edoxaban (DU-176b)
Edoxaban (DU-176b)
Edoxaban (DU-176b)
warfarin
Sponsored by
About this trial
This is an interventional prevention trial for Atrial Fibrillation focused on measuring Anti-coagulant, Non-valvular, Venous Thromboembolism, Prevention of Blood Clots, Atrial Fibrillation, Non-valvular atrial fibrillation
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 to 80 years old.
- Able to provide written informed consent.
- Persistent non-valvular AF supported by abnormal electrocardiogram (ECG)
- A congestive heart failure, hypertension, age ≥ 75 years, diabetes, and prior stroke (CHADS2) index score of at least 2
Exclusion Criteria:
- Subjects with mitral valve disease or previous valvular heart surgery
- Known contraindication to any anticoagulant including vitamin K antagonists such as warfarin
- Known or suspected hereditary or acquired bleeding or coagulation disorder
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Arm Label
1
2
3
4
5
Arm Description
DU-176b 30mg tablet once daily
DU-176b 60mg once daily
DU-176b 30mg b.i.d.
DU-176b 60mg tablets two times a day
warfarin tablets
Outcomes
Primary Outcome Measures
Adjudicated Incidence of Bleeding Events
Adjudicated Incidence of Bleeding Events during treatment period
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities
Secondary Outcome Measures
Incidence of Major Adverse Cardiac Events MACE)
MACE is defined as the composite of stroke [ischemic or hemorrhagic], Systemic embolic event (SEE), Myocardial Infarction (MI), Cardiovascular (CV) death, and hospitalization for any cardiac condition
Effects on Biomarker D-dimer
Mean (SD) change from baseline in D-dimer
Effects on Biomarker Prothrombin Fragments
Mean (SD) change from baseline in Prothrombin Fragments 1 and 2 (F1 and F2)
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Median (min, max) values of Cmin,ss; Cmax,ss
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b
Median (min, max) values of AUCss
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker anti-Factor Xa [FXa] activity on Day 28, 1-3 hours post dose.
Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker endogenous FX activity on Day 28, 1-3 hours post dose.
Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker prothrombinase induced clotting time [PICT] on Day 28, 1-3 hours post dose.
PICT was determined by PICT aasay which is a plasma based functional assay to determine the anticoagulant activity on FXa and FIIa inhibition.
Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker prothrombin time (PT) on Day 28, 1-3 hours post dose.
Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00504556
Brief Title
A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation
Official Title
A Phase 2, Randomized, Parallel Group, Multi Center, Multi National Study for the Evaluation of Safety of Four Fixed Dose Regimens of DU-176b in Subjects With Non- Valvular Atrial Fibrillation
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to assess the safety of a potential new drug DU-176b for the prevention of stroke/systemic embolic event (SEE) in individuals with non-valvular atrial fibrillation (AF). The duration is 3 months of treatment and a 30 day follow-up visit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Thromboembolism
Keywords
Anti-coagulant, Non-valvular, Venous Thromboembolism, Prevention of Blood Clots, Atrial Fibrillation, Non-valvular atrial fibrillation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1146 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
DU-176b 30mg tablet once daily
Arm Title
2
Arm Type
Experimental
Arm Description
DU-176b 60mg once daily
Arm Title
3
Arm Type
Experimental
Arm Description
DU-176b 30mg b.i.d.
Arm Title
4
Arm Type
Experimental
Arm Description
DU-176b 60mg tablets two times a day
Arm Title
5
Arm Type
Active Comparator
Arm Description
warfarin tablets
Intervention Type
Drug
Intervention Name(s)
Edoxaban (DU-176b)
Intervention Description
30mg tablet once daily
Intervention Type
Drug
Intervention Name(s)
Edoxaban (DU-176b)
Intervention Description
60mg tablet once daily
Intervention Type
Drug
Intervention Name(s)
Edoxaban (DU-176b)
Intervention Description
30mg tablet two times a day
Intervention Type
Drug
Intervention Name(s)
Edoxaban (DU-176b)
Intervention Description
60mg tablet two times a day
Intervention Type
Drug
Intervention Name(s)
warfarin
Intervention Description
warfarin tablets
Primary Outcome Measure Information:
Title
Adjudicated Incidence of Bleeding Events
Description
Adjudicated Incidence of Bleeding Events during treatment period
Time Frame
3 months
Title
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
Description
liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Incidence of Major Adverse Cardiac Events MACE)
Description
MACE is defined as the composite of stroke [ischemic or hemorrhagic], Systemic embolic event (SEE), Myocardial Infarction (MI), Cardiovascular (CV) death, and hospitalization for any cardiac condition
Time Frame
3 months
Title
Effects on Biomarker D-dimer
Description
Mean (SD) change from baseline in D-dimer
Time Frame
3 months
Title
Effects on Biomarker Prothrombin Fragments
Description
Mean (SD) change from baseline in Prothrombin Fragments 1 and 2 (F1 and F2)
Time Frame
3 months
Title
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Description
Median (min, max) values of Cmin,ss; Cmax,ss
Time Frame
3 months
Title
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b
Description
Median (min, max) values of AUCss
Time Frame
3 months
Title
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b
Description
Mean (SD) change from baseline in biomarker anti-Factor Xa [FXa] activity on Day 28, 1-3 hours post dose.
Time Frame
Day 28
Title
Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b
Description
Mean (SD) change from baseline in biomarker endogenous FX activity on Day 28, 1-3 hours post dose.
Time Frame
Day 28
Title
Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b
Description
Mean (SD) change from baseline in biomarker prothrombinase induced clotting time [PICT] on Day 28, 1-3 hours post dose.
PICT was determined by PICT aasay which is a plasma based functional assay to determine the anticoagulant activity on FXa and FIIa inhibition.
Time Frame
Day 28
Title
Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b
Description
Mean (SD) change from baseline in biomarker prothrombin time (PT) on Day 28, 1-3 hours post dose.
Time Frame
Day 28
Title
Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b
Description
Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.
Time Frame
Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 to 80 years old.
Able to provide written informed consent.
Persistent non-valvular AF supported by abnormal electrocardiogram (ECG)
A congestive heart failure, hypertension, age ≥ 75 years, diabetes, and prior stroke (CHADS2) index score of at least 2
Exclusion Criteria:
Subjects with mitral valve disease or previous valvular heart surgery
Known contraindication to any anticoagulant including vitamin K antagonists such as warfarin
Known or suspected hereditary or acquired bleeding or coagulation disorder
Facility Information:
City
Huntsville
State/Province
Alabama
Country
United States
City
Anaheim
State/Province
California
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Stockton
State/Province
California
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Sarasota
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Canton
State/Province
Georgia
Country
United States
City
Fort Wayne
State/Province
Indiana
Country
United States
City
Iowa City
State/Province
Iowa
Country
United States
City
Cadillac
State/Province
Michigan
Country
United States
City
Kalispell
State/Province
Montana
Country
United States
City
Fremont
State/Province
Nebraska
Country
United States
City
Santa Fe
State/Province
New Mexico
Country
United States
City
Albany
State/Province
New York
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Allentown
State/Province
Pennsylvania
Country
United States
City
Pottstown
State/Province
Pennsylvania
Country
United States
City
Sellersville
State/Province
Pennsylvania
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Bellevue
State/Province
Washington
Country
United States
City
Minsk
Country
Belarus
City
Brussels
Country
Belgium
City
Genk
Country
Belgium
City
Banja Luka
Country
Bosnia and Herzegovina
City
Mostar
Country
Bosnia and Herzegovina
City
Sarajevo
Country
Bosnia and Herzegovina
City
Tuzla
Country
Bosnia and Herzegovina
City
Calgary
State/Province
Alberta
Country
Canada
City
Edmonton
State/Province
Alberta
Country
Canada
City
Alberta
State/Province
British Columbia
Country
Canada
City
Winnipeg
State/Province
Manitoba
Country
Canada
City
Oshawa
State/Province
Ontario
Country
Canada
City
Thunder Bay
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
Sherbrooke
State/Province
Quebec
Country
Canada
City
Antofagasta
Country
Chile
City
Osorno
Country
Chile
City
Santiago
Country
Chile
City
Temuco
Country
Chile
City
Daugavpils
Country
Latvia
City
Riga
Country
Latvia
City
Ventspils
Country
Latvia
City
Cordoba
Country
Mexico
City
Guadalajara Jalisco
Country
Mexico
City
Mexico City
Country
Mexico
City
Chisinau
Country
Moldova, Republic of
City
Arkhangelsk
Country
Russian Federation
City
Barnaul
Country
Russian Federation
City
Chelyabinsk
Country
Russian Federation
City
Ivanovo
Country
Russian Federation
City
Kaliningrad
Country
Russian Federation
City
Kazan
Country
Russian Federation
City
Kemerovo
Country
Russian Federation
City
Krasnodar
Country
Russian Federation
City
Krasnoyarsk
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
N.Novgorod
Country
Russian Federation
City
Novosibirsk
Country
Russian Federation
City
Orenburg
Country
Russian Federation
City
Penza
Country
Russian Federation
City
Perm
Country
Russian Federation
City
Rostov on Don
Country
Russian Federation
City
Samara
Country
Russian Federation
City
Saratov
Country
Russian Federation
City
St. Petersburg
Country
Russian Federation
City
Tomsk
Country
Russian Federation
City
Tula
Country
Russian Federation
City
Tyumen
Country
Russian Federation
City
Volgograd
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
City
Bardejov
Country
Slovakia
City
Bratislava
Country
Slovakia
City
Kosice
Country
Slovakia
City
Lucenec
Country
Slovakia
City
Presov
Country
Slovakia
City
Cherkassy
Country
Ukraine
City
Chernigov
Country
Ukraine
City
Chernivtsy
Country
Ukraine
City
Dnepropetrovsk
Country
Ukraine
City
Donetsk
Country
Ukraine
City
Ivano-Frankovsk
Country
Ukraine
City
Kiev
Country
Ukraine
City
Lutsk
Country
Ukraine
City
Lviv
Country
Ukraine
City
Odessa
Country
Ukraine
City
Poltava
Country
Ukraine
City
Ternopil
Country
Ukraine
City
Vinnitsa
Country
Ukraine
City
Zaporozhye
Country
Ukraine
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. 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: https://vivli.org/ourmember/daiichi-sankyo/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Learn more about this trial
A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation
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