Safety and Pharmacokinetics Study of DU-176b Administered to Patients With Severe Renal Impairment Undergoing Orthopedic Surgery of The Lower Limbs

• ClinicalTrials.gov Identifier: NCT01857583
• Recruitment Status: Completed
• First Posted: May 20, 2013
• Results First Posted: January 26, 2015
• Last Update Posted: March 5, 2019
• Sponsor: Daiichi Sankyo Co., Ltd.
• Information provided by (Responsible Party): Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Description

Brief Summary:

To assess the safety and pharmacokinetics of DU-176b administered to patients with severe renal impairment undergoing orthopedic surgery of the lower limbs, compared with DU-176b administered to patients with mild renal impairment (MiRI) undergoing orthopedic surgery of the lower limbs.

For reference, the safety of DU-176b in patients with SRI undergoing orthopedic surgery of the lower limbs will be compared with that of fondaparinux.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism	Drug: 15mg DU-176b; Drug: 30mg DU-176b; Drug: Fondaparinux	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Phase III Clinical Study of DU-176b (Venous Thromboembolism): Japanese, Multicenter, Open-label Study of DU-176b in Patients With Severe Renal Impairment (SRI) Undergoing Orthopedic Surgery of the Lower Limbs
• Study Start Date: March 2012
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: SRI 15mg (15 mL/min ≤ CLCR < 20mL/min); Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.	Drug: 15mg DU-176b; Other Name: edoxaban
Experimental: MiRI 30mg (50 mL/min ≤ CLCR ≤ 80mL/min); Mild Renal Impairment group orally administered 30mg DU-176b once daily for 14 days.	Drug: 30mg DU-176b; Other Name: edoxaban
Active Comparator: Fondaparinux (20 mL/min ≤ CLCR < 30mL/min); Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.	Drug: Fondaparinux
Experimental: SRI 15mg (20 mL/min ≤ CLCR < 30mL/min); Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.	Drug: 15mg DU-176b; Other Name: edoxaban

Outcome Measures

Primary Outcome Measures :

1. Incidence of Any Adjudicated Bleeding Events [ Time Frame: 14 days ]
   Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding).
2. Incidence of Adverse Events [ Time Frame: 1 month ]
3. Incidence of Adverse Drug Reactions [ Time Frame: 1 month ]
4. Plasma Concentration of DU-176b [ Time Frame: 14 days ]
5. Plasma Concentration of D21-2393 [ Time Frame: 14 days ]

Secondary Outcome Measures :

1. Incidence of Adjudicated Thromboembolic Events [ Time Frame: 1 month ]
   Incidence of adjudicated thromboembolic events (symptomatic Deep Vein Thrombosis (DVT), symptomatic Pulmonary Thromboembolism (PTE), Venous Thromboembolism (VTE) related deaths).

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients with SRI or MiRI undergoing orthopedic surgery of the lower limbs

Exclusion Criteria:

• Patients who are on hemodialysis or are scheduled to undergo hemodialysis during the study period
• Patients who are at a significantly high risk for bleeding or thromboembolism
• Patients who are receiving another antithrombotic therapy and are unable to suspend the therapy
• Patients who have evidence of hepatic function test abnormalities

Contacts and Locations

Locations

Japan

Toyooka Chuo Hospital

Asahikawa, Hokkaido Prefecture, Japan, 078-8237

Sponsors and Collaborators

Daiichi Sankyo Co., Ltd.

Investigators

• Principal Investigator: Takeshi Fuji, VP; Osaka Koseinenkin Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fuji T, Fujita S, Kawai Y, Abe Y, Kimura T, Fukuzawa M, Abe K, Tachibana S. A randomized, open-label trial of edoxaban in Japanese patients with severe renal impairment undergoing lower-limb orthopedic surgery. Thromb J. 2015 Jan 30;13(1):6. doi: 10.1186/s12959-014-0034-9. eCollection 2015.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01857583
• Other Study ID Numbers: DU176b-B-J306
• First Posted: May 20, 2013
• Results First Posted: January 26, 2015
• Last Update Posted: March 5, 2019
• Last Verified: February 2015

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• 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.
• 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.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):

anticoagulant; DU-176b; edoxaban; factor Xa; oral; orthopedic surgery of lower limbs; severe renal impairment

Additional relevant MeSH terms:

Renal Insufficiency; Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; PENTA; Edoxaban; Fondaparinux; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents