SYNOPSIS
Name ofDaiichi Sankyo Co., Ltd.

Sponsor/Company
Name of Finished Product

LIXIANA TABLETS

Name of Active Ingredient

Edoxaban Tosilate Hydrate

Title of Study

DU-176b Phase III Clinical Study(Venous Thromboembolism)-Randomized Double-Blind Study of DU-176b in Patients
Undergoing Total Hip Arthroplasty with Enoxaparin as an ActiveControl -Investigators

58 investigators

Study Centre(s)58 centers

Publication (reference)

N.A.

Studied Period
Phase of Development

Phase III

Objectives

To verify the non-inferiority of edoxaban to enoxaparin withregard to prevention of venous thromboembolism (VTE) in
patients undergoing total hip arthroplasty.

Methodology

Edoxaban administered at a dose of 30 mg once daily wasassessed

forefficacy

andsafety,comparedwithenoxaparin administered at a dose of 20 mg twice daily,
under a double-blind, double-dummy design. The durationof treatment was set as 11 to 14 days, venography of thelower limbs were performed within 24 hours after thecompletion of administration.
Number of Patients

Planned: 600 subjects (300 subjects per group)(planned and analyzed)

Treatment: 601 subjects (edoxaban group, 303 subjects;
enoxaparin group, 301 subjects)
Efficacy Analyzed: 503 subjects (edoxaban group, 255
subjects; enoxaparin group, 248 subjects)

Diagnosis and Main

Patients who were scheduled for primary THA (excludingCriteria for Inclusionbilateral THA), Patients aged 20 to < 85 years

Test Product, Dose andAdministration of 1 tablet was performed at 6 to 24 hours

Mode of Administration,

after surgery, and 1 tablet/day was administered orally inBatch Number

the morning from the next day (administration interval:
Approximately 10 hours or longer).
Lot number: Edoxaban(30 mg tablets) (DU176F1T07T01)

Edoxaban placebo (DU176F1T07T06)
Duration of Treatment

The duration of treatment was set at 11 to 14 days.

Reference Therapy, Dose

Administration was started with 1 syringe at 24 to 36

andhours after surgery, and 1 syringe was administered

ModeofAdministration,Batch

Numbersubcutaneously twice daily from the next day(administration interval: Approximately 12 hours).
Lot number: Enoxaparin (2000 IU injection) (912004)
Enoxaparin placebo (910918)

Criteria for Evaluation(Efficacy Primary Endpoint)
The primary efficacy outcome was the composite ofsymptomatic and asymptomatic DVT, and PE.
(Safety Primary Endpoint)
The primary safety outcome was the incidence of major or
clinically relevant non-major bleeding.

Statistical Method(Analyses of the Primary Efficacy Endpoint)
The percentage of subjects with at least 1 thromboembolic
event specified as the primary endpoint was analyzed
using the Farrington and Manning method.
(Analyses of the Primary Safety Endpoint)
The incidence of major bleeding or clinically relevant
non-major bleeding during the treatment period (from thestart day of treatment until the day after the last dose)and its 95% CI was calculated for each group ; thedifference in incidence between the edoxaban group andthe enoxaparin group and its 95% CI were also calculated.

Summary - Conclusion(Efficacy Primary Endpoint)
The primary efficacy outcome occurred in 6 of 255 (2.4%)
patients receiving edoxaban and 17 of 248 (6.9%) patients
receiving enoxaparin. (p < 0.001 for non-inferiority; p =0.016 for superiority).No symptomatic DVT or PE wasobserved in both treatment groups.
(Safety Primary Endpoint)
The incidence of major or clinically relevant non-major
bleeding events was 2.6% (8/303) vs 3.7% (11/301) in theedoxaban and enoxaparin groups, respectively (p=0.475).

Major bleeding occurred in 0.7% (2/303) of the edoxabangroup and 2.0% (6/301) of the enoxaparin group (p=0.176).
(Conclusions)This trial demonstrated that oral edoxaban 30 mg once
daily has efficacy superior to enoxaparin in 2,000 IU twice
daily in the prevention of thromboembolic events following
THA with a similar incidence of bleeding events.
Date of Report

25 July, 2014