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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: 15mg DU-176b
* Drug: 30mg DU-176b
* Drug: Fondaparinux


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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). | 14 days | 
| Incidence of Adverse Events |  | 1 month | 
| Incidence of Adverse Drug Reactions |  | 1 month | 
| Plasma Concentration of DU-176b |  | 14 days | 
| Plasma Concentration of D21-2393 |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adjudicated Thromboembolic Events | Incidence of adjudicated thromboembolic events (symptomatic Deep Vein Thrombosis (DVT), symptomatic Pulmonary Thromboembolism (PTE), Venous Thromboembolism (VTE) related deaths). | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulant, DU-176b, edoxaban, factor Xa, oral, orthopedic surgery of lower limbs, severe renal impairment