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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00504556
First received: July 18, 2007
Last updated: March 12, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Thromboembolism
Drug: Edoxaban (DU-176b)
Drug: warfarin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Adjudicated Incidence of Bleeding Events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Adjudicated Incidence of Bleeding Events during treatment period

  • Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities


Secondary Outcome Measures:
  • Incidence of Major Adverse Cardiac Events MACE) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Mean (SD) change from baseline in D-dimer

  • Effects on Biomarker Prothrombin Fragments [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Median (min, max) values of Cmin,ss; Cmax,ss

  • Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Median (min, max) values of AUCss

  • Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.


Enrollment: 1146
Study Start Date: June 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
DU-176b 30mg tablet once daily
Drug: Edoxaban (DU-176b)
30mg tablet once daily
Experimental: 2
DU-176b 60mg once daily
Drug: Edoxaban (DU-176b)
60mg tablet once daily
Experimental: 3
DU-176b 30mg b.i.d.
Drug: Edoxaban (DU-176b)
30mg tablet two times a day
Experimental: 4
DU-176b 60mg tablets two times a day
Drug: Edoxaban (DU-176b)
60mg tablet two times a day
Active Comparator: 5
warfarin tablets
Drug: warfarin
warfarin tablets

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 18 to 80 years old.
  2. Able to provide written informed consent.
  3. Persistent non-valvular AF supported by abnormal electrocardiogram (ECG)
  4. A congestive heart failure, hypertension, age ≥ 75 years, diabetes, and prior stroke (CHADS2) index score of at least 2

Exclusion Criteria:

  1. Subjects with mitral valve disease or previous valvular heart surgery
  2. Known contraindication to any anticoagulant including vitamin K antagonists such as warfarin
  3. Known or suspected hereditary or acquired bleeding or coagulation disorder
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504556

  Show 91 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT00504556     History of Changes
Other Study ID Numbers: DU176b-PRT018
Study First Received: July 18, 2007
Results First Received: February 5, 2015
Last Updated: March 12, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Belarus: Ministry of Health
Bosnia: Central Ethics Committee, Ministarstvo Zdravstva (Ministry of Health)
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Latvia: State Agency of Medicines
Mexico: Federal Commission for Protection Against Health Risks
Moldova: Central Ethics Committee, Drug Agency of Ministry of Health
Russia: Ethics Committee
Slovakia: State Institute for Drug Control
Ukraine: Ministry of Health. Central Ethics Committee

Keywords provided by Daiichi Sankyo Inc.:
Anti-coagulant
Non-valvular
Venous Thromboembolism
Prevention of Blood Clots
Atrial Fibrillation
Non-valvular atrial fibrillation

Additional relevant MeSH terms:
Atrial Fibrillation
Thromboembolism
Arrhythmias, Cardiac
Cardiovascular Diseases
Embolism and Thrombosis
Heart Diseases
Pathologic Processes
Thrombosis
Vascular Diseases
Warfarin
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015