DU-176b Phase 2 Dose Finding Study in Subjects With Non-valvular Atrial Fibrillation

A Phase 2, Randomized, Parallel Group, Multi-Center, Multi-National Study for the Evaluation of Safety and Efficacy of Two Fixed Dosages of DU-176b in Subjects With Non-Valvular Atrial Fibrillation

This study will be conducted in male and female subjects aged 18 to 80 years, inclusive, with non-valvular AF and a CHADS2 Score of at least 1. Subjects will be treated on an outpatient basis. The subjects will be allocated randomly to the open-label warfarin or any double-blind DU-176b dosages. DU-176b will be administered orally for 12 weeks at two fixed doses. Warfarin will be used as active control. Warfarin dosing will be managed and monitored by the Investigator with the dose adjusted to achieve an INR of 2.0 to 3.0, inclusive. The primary endpoints are incidence of major, clinically relevant non-major and minor bleeding events (all bleeding).

Study Overview

• Status: Completed
• Conditions: Stroke; Atrial Fibrillation
• Intervention / Treatment: Drug: DU-176b tablets; Drug: Warfarin tablets

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong-Kong, China
• Korea, Republic of
  • Seoul, Korea, Republic of
• Singapore
  • Singapore, Singapore
• Taiwan
  • Taipei, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects 18 to 80 years of age
• Non-valvular AF supported by abnormal ECG documented for two times (interval of more than 1 week) within 6 months prior to randomization.
• CHADS2 Score of at least 1.

Exclusion Criteria:

• Subjects with mitral valve disease
• Subjects with previous valvular heart surgery
• Contraindication for anticoagulants
• Conditions associated with high risk of bleeding
• Acute coronary syndromes (ACS), percutaneous coronary intervention (PCI), MI, stroke, transient ischemic attack (TIA) or coronary artery/cardiac/other major surgery within the previous 30 days
• Active infective endocarditis or life-expectancy < 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 2; DU-176b tablets: high-dose	Drug: DU-176b tablets; DU-176b tablets taken once daily for up to 3 months
ACTIVE_COMPARATOR: 3; Warfarin tablets	Drug: Warfarin tablets; Warfarin tablets taken once daily for up to 3 months
EXPERIMENTAL: 1; DU-176b tablets: low-dose	Drug: DU-176b tablets; DU-176b tablets taken once daily for up to 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of All Bleeding	Incidence of all bleeding (major, clinically relevant non-major and minor) in two fixed dosage of DU-176b in comparison with warfarin as active control in subjects with non-valvular AF.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluation of Incidence of Major Adverse Cardiovascular Events: Stroke, Systemic Embolic Event, Myocardial Infarction, Cardiovascular Death, and Hospitalization for Any Cardiac Condition	6 months
Evaluation of Effects on Biomarkers of Thrombus Formation	6 months
Evaluation of Plasma Concentration of DU-176	6 months
Evaluation of Effects on Pharmacodynamic Biomarkers	6 months
Evaluation of All Clinical and Laboratory Safety Data.	6 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (ACTUAL): October 1, 2008
• Study Completion (ACTUAL): November 1, 2009

Study Registration Dates

• First Submitted: December 10, 2008
• First Submitted That Met QC Criteria: December 10, 2008
• First Posted (ESTIMATE): December 11, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban; Warfarin
• Other Study ID Numbers: DU176b-C-J226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR