Safety and Pharmacokinetics Study of DU-176b Administered to Non-valvular Atrial Fibrillation With Severe Renal Impairment

Phase III Clinical Study of DU-176b (Non-valvular Atrial Fibrillation): Japanese, Multicenter, Open-label Study of DU-176b in Patients With Non-valvular Atrial Fibrillation and Severe Renal Impairment (SRI)

To assess the safety and pharmacokinetics of DU-176b administered to non-valvular atrial fibrillation patients with severe renal impairment, compared with DU-176b administered to non-valvular atrial fibrillation (NVAF) patients with normal renal function or mild renal impairment (Normal/MiRI).

Study Overview

• Status: Completed
• Conditions: Non-valvular Atrial Fibrillation
• Intervention / Treatment: Drug: DU-176b 15mg; Drug: DU-176b 30mg; Drug: DU-176b 60mg

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 162-0054
    • Tokyo Women's Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with NVAF and SRI, or patients with NVAF and Normal/MiRI.

Exclusion Criteria:

• Patients who are on hemodialysis or patients who may start hemodialysis before the follow-up assessment
• Patients who are at a significantly high risk for bleeding
• Patients who are receiving treatment with any anticoagulant drugs excluding warfarin, rivaroxaban, and dabigatran
• Patients who have evidence of hepatic function test abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRI 15mg; DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks.	Drug: DU-176b 15mg; oral DU-176b 15mg once daily; Other Names: edoxaban
Experimental: Normal/MiRI low-dose group; DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors (body weight of ≤ 60 kg or the presence of concurrent treatment with quinidine or verapamil). DU-176b was orally administered at a dose of 15 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.	Drug: DU-176b 30mg; oral DU-176b 30mg once daily; Other Names: edoxaban
Experimental: Normal/MiRI high-dose group; DU-176b was orally administered at a dose of 60 mg once daily for 12 weeks in subjects who had none of the dose adjustment factors. DU-176b was orally administered at a dose of 30 mg once daily for 12 weeks to subjects who had any of the dose adjustment factors, irrespective of the number of dose adjustment factors.	Drug: DU-176b 60mg; oral DU-176b 60mg once daily; Other Names: edoxaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Any Adjudicated Bleeding Events	Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding)	3 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Investigators: Principal Investigator: Yukihiro Koretsune, Dir, Osaka National Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: atrial fibrillation; anticoagulant; oral; factor Xa; edoxaban; severe renal impairment; DU-176b
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban
• Other Study ID Numbers: DU176b-B-J307

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