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 III study
A DS-7113b immediate release (IR) tablet long-term study inpatients with cancer pain

Investigators-Study Centre(s)14 sites

Publication (reference)
Studied Period

October 2013 – February 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 IR tabletsin patients with cancer pain on opioid analgesics, patients withcancer pain without opioid analgesics, or patients who hadcompleted DS7113-A-J301 study (DS-7113b phase III study, arandomized double-blind comparison study with IR oxycodone inopioid-naive patients with cancer pain) and hoped to continue
administration of DS-7113b tablet

Methodology

A multicenter, open-label, uncontrolled study

Number of Patients (plannedPlanned: 50 subjects

and analyzed)

Analyzed: 48 subjects

Diagnosis and Main Criteria

Inclusion:for Inclusion

・ Patients on opioid analgesics less than 240 mg in morphine
equivalent and judged effective to be treated with strong
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 IR tablets after
completion of the study treatment of DS7113-A-J301 trial(J301 group)・ Patients with an ECOG Performance Status (PS) is ≤ 3, etc.
Exclusion:
・ Patients with symptom(s)/finding(s) falling under thecontraindications or relative contraindications stated in thepackage insert for oxycodone hydrochloride powder andmorphine hydrochloride preparations, etc.
・ Patients with serious hepatic, renal, or respiratory
disorder.
Test Product, Dose and Mode

Test product (batch number):of Administration, Batch

DS-7113b tablet 1 mg（D7113T1H12T05*、D7113T2H13M03）

Number

DS-7113b tablet 2 mg（D7113T1H12T06*、D7113T2H13M06）
DS-7113b tablet 4 mg（D7113T1H12T07*、D7113T2H13M07）*They are also used as rescue medication.
Dosage and Administration:
As in the table below, subjects received a hydromorphone tablet
orally four or six times daily for up to 84 days. The initial dose ofOpioid-use group depended on their pre-opioid daily dose. When it
was judged that a dose increase or reduce was necessary during theperiod of study drug administration, it was possible to increase orreduce the dose step by step.
Daily dose
Opioid-use group
Numberof dailydose
Initialdose

Opioid naïvegroup

6 timesConverted according
to the daily dose of
pre-treatment opioid

J301 group
4 times

4 mg

The dosewhen J301
trial iscompleted

14 mg

4 mg

26 mg8 mg

312 mg12 mg

418 mg

16 mg

524 mg

24 mg

636 mg36 mg

748 mg48 mg

Dosage as rescue medication:
In opioid-based patient group and non-opioid patient group, thedose per rescue medication is administered according to the daily
dose as shown in the table below.
Dose perone rescue medication
11 mg

Duration of Treatment

21 mg

32 mg

43 mg

54 mg

66 mg

78 mg

Treatment period: up to 84 days
Post-treatment observation period: 2 day

Reference Therapy, Dose andModeofNone

Administration,

Batch Number
Criteria for Evaluation

Efficacy: Efficacy rate (post-switch improvement and analgesia
improvement ) 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 ateach evaluate point

Summary - Conclusion

The efficacy rate at FAS was as high as 80.9% at Visit 2 at thetime of evaluation just after initiation of administration, andthat at each evaluation time was almost 80% or more. Elevenof 47 subjects continued to be administered to Visit 8 at thelongest 85th day, and high efficacy rates were maintainedeven for subjects who were continuously administered for along 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.

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 tablet was confirmed to be safe andeffective when used as a regular treatment with a strong opioid
analgesic in patients with various cancer pain and as a rescue
medicine.

Date of Report

March 26, 2018