SYNOPSIS
Name of Sponsor/Company

Daiichi Sankyo Co., Ltd.

Name of Finished Product

NARURAPID® TABLETS

Name of Active Ingredienthydromorphone hydrochloride (INN)

Title of Study

DS-7113b phase II study
A DS-7113b potency ratio assessment study in patients with cancer
pain

Investigators-Study Centre(s)38 sites

Publication (reference)
Studied Period

July 2013 - December 2014

Phase of Development

Phase 2

Objectives

To verify the potency ratio of DS-7113b to morphine, based on thepain control achievement rates following treatment switch toDS-7113b tablets from oral morphine in patients under cancer pain
management. Also, to confirm the efficacy and safety of thetherapy

Methodology

A multicenter, randomized, double-blind, parallel-group study

Number of Patients (plannedPlanned:70 subjects

and analyzed)

Analyzed:70 subjects

Diagnosis and Main Criteria

Inclusion:

for Inclusion

・ Patients with cancer pain whose pain is controlled by 60
mg/day or 90 mg/day of an oral morphine steadly during thescreening period.
・ Patients whose frequency of rescue dose during the screening
period is two or less.
・ Patients with an ECOG PS of ≤ 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 of oral morphine preparations, etc.

Test Product, Dose and Mode

Test product (batch number):of Administration, Batch

DS-7113b tablet 1 mg（D7113T1H12T05）

Number

DS-7113b tablet 1.25 mg（D7113T1H12T08）
DS-7113b tablet 2 mg（D7113T1H12T06）

Dosage and Administration:
The daily dose of each group is as shown in the table below,
depenging on their oral morphine dose during the pre-treatment
observation period.
GroupsConversion
ratio 1:5 group
Conversion
ratio 1:8 group

Daily doseMorphine
60mg/dayMorphine
90mg/day

12 mg

18 mg

7.5 mg

12 mg

The study drug was administered until pain control was achievedor for 5 days, whichever was shorter. The study drug was orallyadministered six times daily in both groups.
Duration of Treatment

Pre-treatment obsevation period: 3 days
Treatment period: 5 days
Post-treatment obsevation period: 2 days

Reference Therapy, Dose andModeofNone

Administration,

Batch Number
Criteria for Evaluation

Efficacy: Pain control ratio (Primary endpoint)
Safety: Adverse event, Clinical laboratory evaluation

Statistical Method

Primary endpoint:

The pain control ratio and its 95% confidence interval (CI) for
each group were calculated. Fisher’s exact test was used tocompare the pain control ratio between groups, and thedifference in the pain control ratio (conversion ratio 1:5 group −conversion ratio 1:8 group) and its 95% CI (two-sided, normalapproximation) were calculated.
Summary - Conclusion

・ The pain control ratio in the FAS was 83.3% in the conversion
ratio 1:5 group and 95.0% in the conversion ratio 1:8 group,with a high pain control ratio achieved in both groups.
・ The incidence of adverse events was 46.7% in the conversion
ratio 1:5 group and 58.5% in the conversion ratio 1:8 group,
showing no significant intergroup difference.
・ Successful pain control was achieved by switching frommorphine to hydromorphone with a conversion ratio of 1:5 or
1:8 in Japanese cancer patients who had achieved pain control
with oral morphine, with no significant difference between
groups. No intergroup difference was observed in theincidence of adverse events or serious adverse events. A
conversion ratio between 1:5 and 1:8 is considered clinicallyappropriate for a switch from morphine to hydromorphone forpain control in cancer patients.
Date of Report

March 26, 2018