SYNOPSIS
Name of Sponsor/Company

Daiichi Sankyo Co., Ltd.

Name of Finished Product

NARUVEIN® INJECTION

Name of Active Ingredienthydromorphone hydrochloride (INN)

Title of Study

DS-7113b injection phase II/III study
A DS-7113b injection open clinical study in patients with cancer
pain (continuous intravenous injection)

Investigators-Study Centre(s)35sitesPublication (reference)-

Studied Period

January 2015 – January 2016

Phase of Development

Phase II/III

Objectives

To evaluate the safety, efficacy and pharmacokinetics following
continuous-administration treatment of DS-7113b injection inpatients with cancer pain on opioid analgesics, patients with cancer
pain without opioid analgesics.

Methodology

A multicenter, open-label, uncontrolled study

Number of Patients (plannedPlanned: 70 subjectsand analyzed)

Analyzed: 69 subjects

Diagnosis and Main Criteria

Inclusion:for Inclusion

・ Patients with cancer pain who have been receiving regularstrong opioids for at least 7 days prior to enrollment(Opioid-use group)・ Patients with cancer pain who have not been on opioid
analgesics, whose Pain Intensity is moderate or severe andVAS is 35 mm and over and judged necessary to be treatedwith strong opioid analgesics (Opioid-naïve 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 morphine and oxycodone hydrochlorideinjections.
・ Patients with serious hepatic, renal, or respiratory
disorder, etc.

Test Product, Dose and Mode

Test product (batch number):of Administration, Batch

DS-7113b injection 2 mg/1mL（D7113I1H14M01A）

Number

DS-7113b injection 20 mg/2mL（D7113I1H14M04A）
Dosage and Administration:
・Opioid-use group: The daily dose of the opioid analgesic in theprevious treatment is converted to the morphine injection
equivalent dose, and 1/8 dose (±20%) is continuously administeredsubcutaneously.
・Opioid-naïve group: Received continuous intravenous doses of
0.5 to 1.0 mg daily.
When it was judged that a dose increase or reduce was necessaryduring the period of study drug administration, it was possible toincrease or reduce the dose step by step.

Duration of Treatment

Treatment period: up to 28 days
Post-treatment observation period: 1 day

Reference Therapy, Dose andModeofNone

Administration,Batch Number
Criteria for Evaluation

Efficacy: Pain control rate (primary endpoint)
Definition of Pain control: If the condition that meets all of thefollowing conditions continues for 2 days until Day 7 ofadministration.
1) The daily dose of DS-7113b is same.
2) Pain intensity is "none" or "mild".
3) Rescue medication less than 4 times a day.
Safety: Adverse event, Clinical laboratory evaluation, etc.

Statistical Method

Primary endpoint:
Pain control rate and its 95% CI were calculated at evaluate point.

Summary - ConclusionThe pain control rate at FAS was 73.9% (51/69). (95%CI =61.9, 83.7)

Rescue medication was evaluated by pain relief (PR) scoreafter 10 minutes rescue administration. As a result, "0. None"
was 19.9% (37/186), and "1. Slight" or more was 80.1%(149/186).

The average value (standard deviation) of the total bodyclearance in steady state was 51.3 (17.4) L / h.

Adverse events observed 40.0%. The main events (expressionrate 5% or more) were somnolence 20.0% (14/70), nausea
10.0% (7/70), constipation 7.1% (5/70), and vomiting 7.1%

(5/70).
As described above, DS-711b injection was confirmed to be safeand effective continuous use as a regular treatment with a strong
opioid analgesic in patients with cancer pain.
Date of Report

October, 4, 2018