SYNOPSIS
Name of Sponsor/Company

Daiichi Sankyo Co., Ltd.

Name of Finished Product

NARUSUS® TABLETS

Name of Active Ingredienthydromorphone hydrochloride (INN)

Title of Study

DS-7113b extended-release (ER) tablet phase III study
A DS-7113b extended-release tablet long-term study in patientswith cancer pain

Investigators-Study Centre(s)16 sites

Publication (reference)
Studied Period

October 2014 – August 2015

Phase of Development

Phase 3

Objectives

To evaluate the safety, efficacy and pharmacokinetics following
long-term (maximum of 84 days) treatment of DS-7113b ER
tablets in patients with cancer pain on opioid analgesics, patientswith cancer pain without opioid analgesics, or patients who hadcompleted DS7113-B-J303 study (DS-7113b extended-release ER
tablet phase III study, a randomized double-blind comparison study
with oxycodone in opioid-naive patients with cancer pain) andhoped to continue administration of DS-7113b ER tablet.

Methodology

A multicenter, open-label, uncontrolled study

Number of Patients (plannedPlanned: 50 subjects

and analyzed)

Analyzed: 50 subjects

Diagnosis and Main Criteria

Inclusion:

for Inclusion

・ Patients on opioid analgesics (oral morphine, oral oxycodone,transdermal fentanyl, or tramadol) less than 240 mg inmorphine equivalent and judged effective to be treated withstrong opioid analgesics (Opioid-use group)・ Patients who have not been on opioid analgesics, whose VAS
is 35 mm and over and judged necessary to be treated withstrong opioid analgesics (Opioid-naïve group)・ Patients who prefer to take DS-7113b ER tablets after
completion of the study treatment of DS7113-B-J303 trial(J303 group)・ Patients with an ECOG Performance Status (PS) is ≤ 3, etc.
Exclusion:
・ Patients with serious hepatic, renal, or respiratorydisorder.
・ Patients with symptom(s)/finding(s) falling under thecontraindications or relative contraindications stated in thepackage insert for oxycodone hydrochloride powder andmorphine hydrochloride preparations, etc.
Test Product, Dose and Mode

Test product (batch number):of Administration, Batch

DS-7113b ER tablet 2 mg（D7113T2H14M01）

Number

DS-7113b ER tablet 6 mg（D7113T2H14M03）
DS-7113b ER tablet 12 mg（D7113T2H14M05）
DS-7113b ER tablet 24 mg（D7113T1H14M07、
D7113T1H14M08）
DS-7113b tablet 1 mg（D7113T2H13M03）
DS-7113b tablet 2 mg（D7113T2H13M06）
DS-7113b tablet 4 mg（D7113T2H13M08）
Dosage and Administration:<Titration period>
Opioid-use

group

andopioid-naïvegroup

receivedahydromorphone tablet orally 4 times or 6 times daily for up to 7
days by the achievement of pain control. The initial dose ofOpioid-use patient group depended on their pre-opioid daily dose,
and the initial dose of opioid-naïve group was 4 mg daily.

<Treatment period>
As in the table below, subjects received a hydromorphone ERtablet orally once daily for up to 84 days. When it was judged thata dose increase or reduce was necessary during the period of study
drug administration, it was possible to increase or reduce the dose
step by step.
Daily dose
Opioid-use group
Initialdose

Opioid-naïvegroup

DS-7113b daily dose after
achieving pain control

14 mg

26 mg

38 mg

412 mg

518 mg

J303 group
The dosewhen J303
trial iscompletedDuration of Treatment

624 mg

736 mg

848 mgTitration period: up to 7 days
Treatment period: up to 84 days
Post-treatment observation period: 1 day

Reference Therapy, Dose andModeofNone

Administration,Batch Number
Criteria for Evaluation

Efficacy: Efficacy rate (post-switch improvement and analgesiaimprovement ) at each visit and early termination visit (Primaryendpoint) , use of rescue medication
Safety: Adverse event, Clinical laboratory evaluation

Statistical Method

Primary endpoint:
Efficacy rate and its 95% CI were calculated at each evaluate point.

Summary - Conclusion

The efficacy rate at FAS was as high as 78.0% at Visit 2 at thetime of evaluation just after initiation of DS-7113b ER tablet
administration, and that at each evaluation time was almost
70% or more. Twenty of 50 subjects continued to beadministered to Visit 8, and high efficacy rates weremaintained even for subjects who were continuously
administered for a long period of time.

Regarding safety, most adverse events observed were eventscommonly associated with the original disease or eventscommonly observed when opioid analgesics were used,
except for safety issues to be noted when using strong opioid
analgesics noteworthy things were not recognized.

In addition to the scheduled administration of DS-7113b ERtablets, even when DS-7113b tablet was administered as a
rescue medicine, no noteworthy safety problem was noticed.
A significant pain improvement was confirmed for its
effectiveness as a rescue medicine.

As described above, DS-711b ER tablet was confirmed to be safeand effective for-long-term use as a regular treatment with a strong
opioid analgesic in patients with various cancer pain.
Date of Report

March 26, 2018