Efficacy and Safety of Naldemedine in the Treatment of Opioid-induced Constipation

Opioid-induced Constipation Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Naldemedine in the Treatment of Opioid-induced Constipation in Subjects With Non-malignant Chronic Pain Receiving Opioid Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01965158
• Other study ID #: 1314V9231
• Status: Completed
• Phase: Phase 3
• First received: September 30, 2013
• Last updated: May 5, 2016
• Start date: August 2013
• Est. completion date: October 2015

Study information

• Verified date: April 2016
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of naldemedine in the treatment of opioid-induced constipation (OIC) in subjects with non-malignant chronic pain who are not using laxatives

Description:

This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of naldemedine 0.2 mg once daily versus placebo for the treatment of subjects with non-malignant chronic pain and OIC

Recruitment information / eligibility

• Status: Completed
• Enrollment: 540
• Est. completion date: October 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subjects aged 18 to 80 years inclusive at the time of informed consent

2. Subjects must have non-malignant chronic pain treated with opioids and must have opioid-induced constipation (OIC)

3. Subjects must be treated with a stable opioid regimen at a total daily dose on average of = 30 mg equivalents of oral morphine sulfate

4. Subjects must not be currently using laxatives or must be willing to discontinue laxative use at Screening and must be willing to use only the rescue laxatives provided throughout the study duration

5. Subjects must meet opioid-induced constipation criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary

Exclusion Criteria:

1. Evidence of significant structural abnormalities of the gastrointestinal (GI) tract

2. Evidence of active medical diseases affecting bowel transit

3. History or presence of pelvic disorders that may be a cause of constipation

4. Surgery (except for minor procedures) within 60 days of Screening

5. History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation (e.g., mechanical GI obstruction)

6. Subjects who have never taken laxatives for the treatment of OIC

7. History of active treatment for cancer within the last 2 years (except for basal cell or squamous cell carcinoma of the skin that have been successfully resected) or tamoxifen [Nolvadex®] and raloxifene [Evista®] when being used for prevention of breast cancer

8. Current use of any prohibited medication including opioid antagonists, partial agonists or mixed agonists/antagonists

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Constipation
• Opioid-induced Constipation

Intervention

Drug:
• Naldemedine
Naldemedine tablet from weeks 1-12
• Placebo
Placebo tablet from weeks 1-12

Locations

Country	Name	City	State
Austria	Shionogi Research Site	St. Poelten
Austria	Shionogi Research Site	Vienna
Czech Republic	Shionogi Research Site	Hradec Kralove
Czech Republic	Shionogi Research Site	Liberec
Czech Republic	Shionogi Research Site	Pardubice
Czech Republic	Shionogi Research Site	Prague
Czech Republic	Shionogi Research Site	Vysoke Myto
Germany	Shionogi Research Site	Berlin
Germany	Shionogi Research Site	Eichstaett
Germany	Shionogi Research Site	Frankfurt am Main
Poland	Shionogi Research Site	Bialystok
Poland	Shionogi Research Site	Bydgoszcz
Poland	Shionogi Research Site	Czeladz
Poland	Shionogi Research Site	Gorzów Wielkopolski
Poland	Shionogi Research Site	Warszawa
Spain	Shionogi Research Site	Alicante
Spain	Shionogi Research Site	Cádiz
Spain	Shionogi Research Site	Madrid
United Kingdom	Shionogi Research Site	Belfast
United Kingdom	Shionogi Research Site	Bexhill-on-Sea East Sussex
United Kingdom	Shionogi Research Site	Crownhill Plymouth
United Kingdom	Shionogi Research Site	Fowey Cornwall
United Kingdom	Shionogi Research Site	Liskeard Cornwall
United Kingdom	Shionogi Research Site	London
United Kingdom	Shionogi Research Site	Penzance Cornwall
United Kingdom	Shionogi Research Site	Soham Ely Cambs
United Kingdom	Shionogi Research Site	St Austell Cornwall
United Kingdom	Shionogi Research Site	Tomairt
United States	Shionogi Research Site	Albuquerque	New Mexico
United States	Shionogi Research Site	Arlington	Texas
United States	Shionogi Research Site	Austin	Texas
United States	Shionogi Research Site	Belividere	New Jersey
United States	Shionogi Research Site	Birmington	Alabama
United States	Shionogi Research Site	Caro	Michigan
United States	Shionogi Research Site	Chattanooga	Tennessee
United States	Shionogi Research Site	Cincinnati	Ohio
United States	Shionogi Research Site	Dallas	Texas
United States	Shionogi Research Site	East Brunswick	New Jersey
United States	Shionogi Research Site	Flint	Michigan
United States	Shionogi Research Site	Fresno	California
United States	Shionogi Research Site	Golden	Colorado
United States	Shionogi Research Site	Great Neck	New York
United States	Shionogi Research Site	Hazelwood	Missouri
United States	Shionogi Research Site	Hollis	New York
United States	Shionogi Research Site	Houstan	Texas
United States	Shionogi Research Site	Las Vegas	Nevada
United States	Shionogi Research Site	Long Beach	California
United States	Shionogi Research Site	Marietta	Georgia
United States	Shionogi Research Site	Medford	Oregon
United States	Shionogi Research Site	Miami	Florida
United States	Shionogi Research Site	Miami Springs	Florida
United States	Shionogi Research Site	National City	California
United States	Shionogi Research Site	New Windsor	New York
United States	Shionogi Research Site	North Hollywood	California
United States	Shionogi Research Site	Oceanside	California
United States	Shionogi Research Site	Oklahoma City	Oklahoma
United States	Shionogi Research Site	Orlando	Florida
United States	Shionogi Research Site	Phoenix	Arizona
United States	Shionogi Research Site	San Antonio	Texas
United States	Shionogi Research Site	Sarasota	Florida
United States	Shionogi Research Site	Shreveport	Louisiana
United States	Shionogi Research Site	West Palm Beach	Florida
United States	Shionogi Research Site	West Reading	Pennsylvania
United States	Shionogi Research Site	Winston-Salem	North Carolina
United States	Shionogi Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Countries where clinical trial is conducted

United States,  Austria,  Czech Republic,  Germany,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of responders	The primary efficacy endpoint will be the proportion of responders where a responder is defined as of having 9 positive response weeks or more out of the 12 week Treatment Period and 3 positive response weeks out of last 4 weeks of the 12 week Treatment Period. A positive response week will be defined as = 3 spontaneous bowel movements (SBM) per week and an increase from baseline of = 1 SBM per week for that week.	12 week treatment period	No