Back to resultsEfficacy and Safety of Naldemedine in the Treatment of Opioid-induced Constipation
Primary Purpose
Opioid-induced Constipation
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Naldemedine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Opioid-induced Constipation focused on measuring Opioid-induced Constipation
Eligibility Criteria
Inclusion Criteria:
- Subjects aged 18 to 80 years inclusive at the time of informed consent
- Subjects must have non-malignant chronic pain treated with opioids and must have opioid-induced constipation (OIC)
- Subjects must be treated with a stable opioid regimen at a total daily dose on average of ≥ 30 mg equivalents of oral morphine sulfate
- 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
- Subjects must meet opioid-induced constipation criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary
Exclusion Criteria:
- Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
- Evidence of active medical diseases affecting bowel transit
- History or presence of pelvic disorders that may be a cause of constipation
- Surgery (except for minor procedures) within 60 days of Screening
- 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)
- Subjects who have never taken laxatives for the treatment of OIC
- 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
- Current use of any prohibited medication including opioid antagonists, partial agonists or mixed agonists/antagonists
Sites / Locations
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
- Shionogi Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Naldemedine
Placebo
Arm Description
Participants received 0.2 mg naldemedine orally once daily for 12 weeks.
Participants received matching placebo orally once daily for 12 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of rescue laxative therapy during the 24 hours prior to the BM.
A responder was defined as a participant having 9 or more positive response weeks 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 was defined as ≥ 3 SBMs per week and an increase from baseline of ≥ 1 SBM per week for that week. If a participant had less than 4 days of diary entries for a week, that week was treated as a "non-response" week.
Any participant with insufficient primary endpoint data (data for less than 9 out of 12 weeks of the Treatment Period or less than 3 out of the last 4 weeks of the 12-week Treatment Period) was treated as a non-responder.
Secondary Outcome Measures
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM.
Baseline was defined as the 14 days in the screening period prior to study drug administration.
Change From Baseline to Week 1 in the Number of Spontaneous Bowel Movements Per Week
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM.
Baseline was defined as the 14 days in the screening period prior to study drug administration.
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements Per Week
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. A complete spontaneous bowel movement (CSBM) was defined as an SBM which was accompanied by the feeling of complete evacuation.
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements With No Straining Per Week
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation.
The severity of straining with each bowel movement was assessed on the following scale: 0=no straining, 1=mild straining, 2=moderate straining, 3=severe straining, 4=very severe straining. SBMs without straining were defined as SBMs with a straining score of 0.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01965158
Brief Title
Efficacy and Safety of Naldemedine in the Treatment of Opioid-induced Constipation
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
August 29, 2013 (Actual)
Primary Completion Date
January 22, 2015 (Actual)
Study Completion Date
January 22, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shionogi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of naldemedine in the treatment of opioid-induced constipation (OIC) in adults with non-malignant chronic pain who are not using laxatives.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-induced Constipation
Keywords
Opioid-induced Constipation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
547 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Naldemedine
Arm Type
Experimental
Arm Description
Participants received 0.2 mg naldemedine orally once daily for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received matching placebo orally once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Naldemedine
Other Intervention Name(s)
S 297995, Symproic®
Intervention Description
Naldemedine 0.2 mg tablet taken orally once a day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablet taken orally once a day
Primary Outcome Measure Information:
Title
Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response
Description
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of rescue laxative therapy during the 24 hours prior to the BM.
A responder was defined as a participant having 9 or more positive response weeks 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 was defined as ≥ 3 SBMs per week and an increase from baseline of ≥ 1 SBM per week for that week. If a participant had less than 4 days of diary entries for a week, that week was treated as a "non-response" week.
Any participant with insufficient primary endpoint data (data for less than 9 out of 12 weeks of the Treatment Period or less than 3 out of the last 4 weeks of the 12-week Treatment Period) was treated as a non-responder.
Time Frame
12-week treatment period
Secondary Outcome Measure Information:
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
Description
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM.
Baseline was defined as the 14 days in the screening period prior to study drug administration.
Time Frame
Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)
Title
Change From Baseline to Week 1 in the Number of Spontaneous Bowel Movements Per Week
Description
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of a rescue laxative therapy during the 24 hours prior to the BM.
Baseline was defined as the 14 days in the screening period prior to study drug administration.
Time Frame
Baseline and Week 1
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements Per Week
Description
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. A complete spontaneous bowel movement (CSBM) was defined as an SBM which was accompanied by the feeling of complete evacuation.
Time Frame
Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements With No Straining Per Week
Description
A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation.
The severity of straining with each bowel movement was assessed on the following scale: 0=no straining, 1=mild straining, 2=moderate straining, 3=severe straining, 4=very severe straining. SBMs without straining were defined as SBMs with a straining score of 0.
Time Frame
Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects aged 18 to 80 years inclusive at the time of informed consent
Subjects must have non-malignant chronic pain treated with opioids and must have opioid-induced constipation (OIC)
Subjects must be treated with a stable opioid regimen at a total daily dose on average of ≥ 30 mg equivalents of oral morphine sulfate
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
Subjects must meet opioid-induced constipation criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary
Exclusion Criteria:
Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
Evidence of active medical diseases affecting bowel transit
History or presence of pelvic disorders that may be a cause of constipation
Surgery (except for minor procedures) within 60 days of Screening
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)
Subjects who have never taken laxatives for the treatment of OIC
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
Current use of any prohibited medication including opioid antagonists, partial agonists or mixed agonists/antagonists
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shionogi Clinical Trials Administrator Clinical Support Help Line
Organizational Affiliation
Shionogi
Official's Role
Study Director
Facility Information:
Facility Name
Shionogi Research Site
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Shionogi Research Site
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Shionogi Research Site
City
Fresno
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Long Beach
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
National City
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
North Hollywood
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Oceanside
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Golden
State/Province
Colorado
Country
United States
Facility Name
Shionogi Research Site
City
Miami Springs
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Miami
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Sarasota
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
West Palm Beach
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Winter Park
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Marietta
State/Province
Georgia
Country
United States
Facility Name
Shionogi Research Site
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Shionogi Research Site
City
Caro
State/Province
Michigan
Country
United States
Facility Name
Shionogi Research Site
City
Flint
State/Province
Michigan
Country
United States
Facility Name
Shionogi Research Site
City
Hazelwood
State/Province
Missouri
Country
United States
Facility Name
Shionogi Research Site
City
Las Vegas
State/Province
Nevada
Country
United States
Facility Name
Shionogi Research Site
City
Belvidere
State/Province
New Jersey
Country
United States
Facility Name
Shionogi Research Site
City
East Brunswick
State/Province
New Jersey
Country
United States
Facility Name
Shionogi Research Site
City
Albuquerque
State/Province
New Mexico
Country
United States
Facility Name
Shionogi Research Site
City
Great Neck
State/Province
New York
Country
United States
Facility Name
Shionogi Research Site
City
Hollis
State/Province
New York
Country
United States
Facility Name
Shionogi Research Site
City
New Windsor
State/Province
New York
Country
United States
Facility Name
Shionogi Research Site
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
Shionogi Research Site
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Shionogi Research Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Shionogi Research Site
City
Medford
State/Province
Oregon
Country
United States
Facility Name
Shionogi Research Site
City
West Reading
State/Province
Pennsylvania
Country
United States
Facility Name
Shionogi Research Site
City
Chattanooga
State/Province
Tennessee
Country
United States
Facility Name
Shionogi Research Site
City
Arlington
State/Province
Texas
Country
United States
Facility Name
Shionogi Research Site
City
Austin
State/Province
Texas
Country
United States
Facility Name
Shionogi Research Site
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Shionogi Research Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
Shionogi Research Site
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Shionogi Research Site
City
St. Poelten
Country
Austria
Facility Name
Shionogi Research Site
City
Vienna
Country
Austria
Facility Name
Shionogi Research Site
City
Hradec Kralove
Country
Czechia
Facility Name
Shionogi Research Site
City
Liberec
Country
Czechia
Facility Name
Shionogi Research Site
City
Pardubice
Country
Czechia
Facility Name
Shionogi Research Site
City
Prague
Country
Czechia
Facility Name
Shionogi Research Site
City
Vysoke Myto
Country
Czechia
Facility Name
Shionogi Research Site
City
Berlin
Country
Germany
Facility Name
Shionogi Research Site
City
Eichstaett
Country
Germany
Facility Name
Shionogi Research Site
City
Frankfurt am Main
Country
Germany
Facility Name
Shionogi Research Site
City
Bialystok
Country
Poland
Facility Name
Shionogi Research Site
City
Bydgoszcz
Country
Poland
Facility Name
Shionogi Research Site
City
Czeladź
Country
Poland
Facility Name
Shionogi Research Site
City
Gorzów Wielkopolski
Country
Poland
Facility Name
Shionogi Research Site
City
Warszawa
Country
Poland
Facility Name
Shionogi Research Site
City
Alicante
Country
Spain
Facility Name
Shionogi Research Site
City
Cádiz
Country
Spain
Facility Name
Shionogi Research Site
City
Madrid
Country
Spain
Facility Name
Shionogi Research Site
City
Belfast
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Bexhill-on-Sea East Sussex
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Crownhill Plymouth
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Fowey Cornwall
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Liskeard Cornwall
Country
United Kingdom
Facility Name
Shionogi Research Site
City
London
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Penzance Cornwall
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Soham Ely Cambs
Country
United Kingdom
Facility Name
Shionogi Research Site
City
St Austell Cornwall
Country
United Kingdom
Facility Name
Shionogi Research Site
City
Tomairt
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
34377150
Citation
Hale ME, Wild JE, Yamada T, Yokota T, Tack J, Andresen V, Drewes AM. Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives. Therap Adv Gastroenterol. 2021 Jul 31;14:17562848211032320. doi: 10.1177/17562848211032320. eCollection 2021.
Results Reference
derived
PubMed Identifier
34295186
Citation
Camilleri M, Hale M, Morlion B, Tack J, Webster L, Wild J. Naldemedine Improves Patient-Reported Outcomes of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain in the COMPOSE Phase 3 Studies. J Pain Res. 2021 Jul 16;14:2179-2189. doi: 10.2147/JPR.S282738. eCollection 2021.
Results Reference
derived
PubMed Identifier
33965574
Citation
Tack J, Camilleri M, Hale M, Morlion B, Nalamachu S, Webster L, Wild J. Establishing Minimal Clinically Important Differences in Quality of Life Measures in Opioid-Induced Constipation. Clin Gastroenterol Hepatol. 2022 Apr;20(4):855-863. doi: 10.1016/j.cgh.2021.05.004. Epub 2021 Aug 5.
Results Reference
derived
PubMed Identifier
32280263
Citation
Webster LR, Hale ME, Yamada T, Wild JE. A Renal Impairment Subgroup Analysis of the Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy. J Pain Res. 2020 Mar 24;13:605-612. doi: 10.2147/JPR.S237833. eCollection 2020.
Results Reference
derived
PubMed Identifier
32086791
Citation
Wild J, Webster L, Yamada T, Hale M. Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy: A Subgroup Analysis of Patients >/= 65 Years of Age. Drugs Aging. 2020 Apr;37(4):271-279. doi: 10.1007/s40266-020-00753-2.
Results Reference
derived
PubMed Identifier
31145214
Citation
Wild J, Yamada T, Arjona Ferreira JC, Hale M. Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials. Pain. 2019 Oct;160(10):2358-2364. doi: 10.1097/j.pain.0000000000001629.
Results Reference
derived
PubMed Identifier
28576452
Citation
Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):555-564. doi: 10.1016/S2468-1253(17)30105-X. Epub 2017 May 30.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Naldemedine in the Treatment of Opioid-induced Constipation
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