Opioid-induced ConstipationPhase 3NCT01965652
Long Term Safety of Naldemedine
A Phase 3 study testing Naldemedine in people with Opioid-induced Constipation, run by Shionogi at 186 sites in 16 countries.
Trial summary
The purpose of this study is to evaluate the long-term safety of naldemedine for the treatment of constipation due to opioid therapy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Opioid-induced Constipation
- What is being tested?
- Naldemedine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,246 participants
- Where
- 186 sitesin 16 countries
- Study dates
- 24 Sep 2013to 12 Jan 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects aged 18 to 80 years inclusive at the time of informed consent
- Subjects must have non-malignant chronic pain treated 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 may or may not be on a routine laxative regimen at the time of Screening
Who cannot join
- Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
- Evidence of active medical diseases affecting bowel transit
- History 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
- Current use of any prohibited medication including opioid antagonists, partial or mixed agonists/antagonists
Trial locations and contacts
186 sites in 16 countries.
186 sites in 16 countries
United States99 sites
Shionogi Research Site
Akron, Ohio
Shionogi Research Site
Albuquerque, New Mexico
Shionogi Research Site
Atlanta, Georgia
Shionogi Research Site
Augusta, Kansas
Shionogi Research Site
Aurora, Illinois
Shionogi Research Site
Austin, Texas
Shionogi Research Site
Bellevue, Washington
Shionogi Research Site
Biloxi, Mississippi
Shionogi Research Site
Birmingham, Alabama
Shionogi Research Site
Bloomington, Illinois
Shionogi Research Site
Blue Ridge, Georgia
Shionogi Research Site
Boise, Idaho
Shionogi Research Site
Bountiful, Utah
Shionogi Research Site
Boynton Beach, Florida
Shionogi Research Site
Brandon, Florida
Shionogi Research Site
Bristol, Tennessee
Shionogi Research Site
Brockton, Massachusetts
Shionogi Research Site
Brooksville, Florida
Shionogi Research Site
Canton, Ohio
Shionogi Research Site
Chandler, Arizona
Shionogi Research Site
Charleston, South Carolina
Shionogi Research Site
Clearwater, Florida
Shionogi Research Site
Colorado Springs, Colorado
Shionogi Research Site
Columbus, Ohio
Shionogi Research Site
Dallas, Texas
Shionogi Research Site
Decatur, Georgia
Shionogi Research Site
Decatur, Illinois
Shionogi Research Site
Edmonds, Washington
Shionogi Research Site
Eunice, Louisiana
Shionogi Research Site
Evansville, Indiana
Shionogi Research Site
Fall River, Massachusetts
Shionogi Research Site
Fort Myers, Florida
Shionogi Research Site
Fountain Valley, California
Shionogi Research Site
Fremont, Nebraska
Shionogi Research Site
Garden Grove, California
Shionogi Research Site
Glendale, Arizona
Shionogi Research Site
Glendale, California
Shionogi Research Site
Goodyear, Arizona
Shionogi Research Site
Greensboro, North Carolina
Shionogi Research Site
Greer, South Carolina
Shionogi Research Site
Groveport, Ohio
Shionogi Research Site
Hartford, Kentucky
Shionogi Research Site
Henderson, Nevada
Shionogi Research Site
Houston, Texas
Shionogi Research Site
Huntingdon Valley, Pennsylvania
Shionogi Research Site
Hurst, Texas
Shionogi Research Site
Jacksonville, Florida
Shionogi Research Site
Jenkintown, Pennsylvania
Shionogi Research Site
Kettering, Ohio
Shionogi Research Site
Lafayette, Indiana
Shionogi Research Site
Lake Charles, Louisiana
Shionogi Research Site
Lake City, Florida
Shionogi Research Site
Lakeland, Florida
Shionogi Research Site
Lansdale, Pennsylvania
Shionogi Research Site
Las Vegas, Nevada
Shionogi Research Site
Lebanon, Ohio
Shionogi Research Site
Long Beach, California
Shionogi Research Site
Los Angeles, California
Shionogi Research Site
Mandeville, Louisiana
Shionogi Research Site
Marion, Ohio
Shionogi Research Site
Mesa, Arizona
Shionogi Research Site
Milan, Tennessee
Shionogi Research Site
Mobile, Alabama
Shionogi Research Site
Munroe Falls, Ohio
Shionogi Research Site
Myrtle Beach, South Carolina
Shionogi Research Site
Nashville, Tennessee
Shionogi Research Site
New Bedford, Massachusetts
Shionogi Research Site
New York, New York
Shionogi Research Site
Newton, Kansas
Shionogi Research Site
Oceanside, California
Shionogi Research Site
Oklahoma City, Oklahoma
Shionogi Research Site
Omaha, Nebraska
Shionogi Research Site
Orlando, Florida
Shionogi Research Site
Phoenix, Arizona
Shionogi Research Site
Portland, Oregon
Shionogi Research Site
Richmond, Virginia
Shionogi Research Site
Rochester, Michigan
Shionogi Research Site
Rockford, Illinois
Shionogi Research Site
Sacramento, California
Shionogi Research Site
Saginaw, Michigan
Shionogi Research Site
Salt Lake City, Utah
Shionogi Research Site
Santa Ana, California
Shionogi Research Site
Savannah, Georgia
Shionogi Research Site
Schaumburg, Illinois
Shionogi Research Site
South Miami, Florida
Shionogi Research Site
South Ogden, Utah
Shionogi Research Site
St. Petersburg, Florida
Shionogi Research Site
Sugar Land, Texas
Shionogi Research Site
Summerville, South Carolina
Shionogi Research Site
Tampa, Florida
Shionogi Research Site
Traverse City, Michigan
Shionogi Research Site
Trenton, New Jersey
Shionogi Research Site
Tucson, Arizona
Shionogi Research Site
Tulsa, Oklahoma
Shionogi Research Site
Upland, California
Shionogi Research Site
Valparaiso, Indiana
Shionogi Research Site
Wichita, Kansas
Shionogi Research Site
Wilmington, North Carolina
Shionogi Research Site
Winston-Salem, North Carolina
United Kingdom18 sites
Shionogi Research Site
Bath
Shionogi Research Site
Belfast
Shionogi Research Site
Bexhill on Sea East Sussex
Shionogi Research Site
Chesterfield
Shionogi Research Site
Chestfield Kent
Shionogi Research Site
Daventry Northants
Shionogi Research Site
Devon
Shionogi Research Site
Epworth Doncaster
Shionogi Research Site
Harrogate
Shionogi Research Site
Hinckley
Shionogi Research Site
Liverpool
Shionogi Research Site
Norwich
Shionogi Research Site
Oldham
Shionogi Research Site
Peterborough
Shionogi Research Site
Randalstown, County Antrim
Shionogi Research Site
Spiro Close, Pulborough West Sussex
Shionogi Research Site
Wellingborough Northamptonshire
Shionogi Research Site
York
Germany11 sites
Shionogi Research Site
Berlin
Shionogi Research Site
Dresden
Shionogi Research Site
Halle
Shionogi Research Site
Hamburg
Shionogi Research Site
Hanover
Shionogi Research Site
Kassel
Shionogi Research Site
Leipzig
Shionogi Research Site
Lünen
Shionogi Research Site
Mainz
Shionogi Research Site
Münster
Shionogi Research Site
Stadtroda
Australia9 sites
Shionogi Research Site
Adelaide
Shionogi Research Site
Bedford Park
Shionogi Research Site
Camperdown
Shionogi Research Site
Carina Heights
Shionogi Research Site
Caulfield South
Shionogi Research Site
Malvern East
Shionogi Research Site
Nambour
Shionogi Research Site
Sherwood
Shionogi Research Site
St Leonards
Italy8 sites
Shionogi Research Site
Asti
Shionogi Research Site
Catania
Shionogi Research Site
Chieti
Shionogi Research Site
Florence
Shionogi Research Site
Naples
Shionogi Research Site
Rionero in Vulture
Shionogi Research Site
Roma
Shionogi Research Site
Rome
Canada6 sites
Shionogi Research Site
London
Shionogi Research Site
Mirabel
Shionogi Research Site
Sarnia
Shionogi Research Site
Sherbrooke
Shionogi Research Site
Toronto
Shionogi Research Site
Vancouver
Czechia5 sites
Shionogi Research Site
Benešov
Shionogi Research Site
Olomouc
Shionogi Research Site
Ostrava
Shionogi Research Site
Pardubice
Shionogi Research Site
Pribram V- Zdabor
Hungary5 sites
Shionogi Research Site
Balatonfüred
Shionogi Research Site
Budapest
Shionogi Research Site
Debrecen
Shionogi Research Site
Hatvan
Shionogi Research Site
Szikszó
South Africa5 sites
Shionogi Research Site
Alberton
Shionogi Research Site
Lyttelton Centurion
Shionogi Research Site
Muckleneuk Pretoria
Shionogi Research Site
Pretoria West Pretoria
Shionogi Research Site
Worcester
Israel4 sites
Shionogi Research Site
Beersheba
Shionogi Research Site
Haifa
Shionogi Research Site
Tel Aviv
Shionogi Research Site
Tel HaShomer
Poland4 sites
Shionogi Research Site
Chorzów
Shionogi Research Site
Gdansk
Shionogi Research Site
Katowice
Shionogi Research Site
Lublin
Austria3 sites
Shionogi Research Site
Linz
Shionogi Research Site
Vienna
Shionogi Research Site
Zams
Denmark3 sites
Shionogi Research Site
Glostrup Municipality
Shionogi Research Site
Hellerup
Shionogi Research Site
Odense
Spain3 sites
Shionogi Research Site
Barcelona
Shionogi Research Site
Girona
Shionogi Research Site
Seville
About this study
Official title: A Randomized Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study to Evaluate the Long-term Safety of Naldemedine for the Treatment of Opioid-induced Constipation in Subjects With Non-malignant Chronic Pain Receiving Opioid Therapy
The purpose of this study is to evaluate the long-term safety of naldemedine for the treatment of constipation due to opioid therapy.
- Conditions
- Opioid-induced Constipation
- Being tested
- Naldemedine, Placebo
- Keywords
- Opioid Induced Constipation
- Medical subject headings
- Opioid-Induced Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaldemedineDrug
Also called S-297995, Symproic®
Naldemedine 0.2 mg tablet taken orally once a day
PlaceboDrug
Placebo tablet taken orally once a day
| Study group | Role | What they receive |
|---|---|---|
| Naldemedine | Experimental | Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks. Receives: Drug: Naldemedine |
| Placebo | Placebo comparator | Participants received matching placebo tablets orally once daily for 52 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
A serious adverse event was defined as any adverse event (AE) that resulted in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life threatening, or require hospitalization were considered an SAE when, based upon appropriate medical judgment, they jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.
Adverse drug reactions (ADRs) were defined as adverse events that were considered by the investigator to be definitely, probably, or possibly related to study drug. Serious ADRs were defined as serious AEs considered by the investigator to be definitely, probably, or possibly related to study drug.
Measured: From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).
Secondary outcomes (12)
Change From Baseline in the Number of Bowel Movements Per Week
Participants monitored their bowel movements and completed a daily bowel habits diary the week prior to study visits (i.e. during Weeks 11, 23, 35, and 51).
Measured: Baseline and Weeks 12, 24, 36, and 52
Percentage of Participants Meeting Each Criterion of Laxative Use
Participants who were taking stable routine/regular laxatives at Screening were to continue taking the same regimen throughout the study.
The percentage of participants meeting each of the criteria below are reported:
- Participants not on stable laxatives, defined as participants who did not use laxatives from 28 days prior to the Screening Period to the final dose of study drug or who received only rescue laxative. Rescue is defined as any laxative taken for the first time during the Treatment Period.
1a. Out of participants who were not on stable laxatives, participants who received rescue laxatives.
- Participants on stable laxatives, defined as participants who may have had at least one/any stable laxative use reported from 28 days prior to Screening Period to the final dose of study drug.
2a. Out of participants who were on stable laxatives, participants who received rescue laxatives.
- Participants who did not meet criteria 1 or 2.
Measured: From 28 days prior to screening until the end of the treatment period (total of 56 weeks)
Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms
The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The overall score was calculated as the mean of all 12 items and ranges from 0 (best) to 4 (worst). A negative change from baseline value indicates improvement.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score
The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The abdominal-symptom domain score was calculated as the mean of the following 4 items: abdominal discomfort, abdominal pain, abdominal bloating and stomach cramps.
A negative change from baseline value indicates improvement in symptoms.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score
The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The abdominal-symptom domain score was calculated as the mean of the following 3 items: painful bowel movements, rectal burning during or after a bowel movement, and rectal bleeding or tearing during or after a bowel movement. A negative change from baseline value indicates improvement in symptoms.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the PAC-SYM Stool-symptoms Domain Score
The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The stool-symptom domain score was calculated as the mean of the following 5 items: incomplete bowel movements, bowel movements that were too hard, bowel movements that were too small, straining or squeezing to try to pass bowel movements, and false-alarm bowel movements.
A negative change from baseline value indicates improvement in symptoms.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score
The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants' daily life during the past 2 weeks.
Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The overall score was calculated as the mean of all 28 item scores. A negative change from baseline value indicates improvement.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Physical Discomfort Domain of PAC-QOL
The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants' daily life during the past 2 weeks.
Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The physical discomfort domain consists of 4 questions related to bloating, feeling heavy, how much of the time participants felt any physical discomfort and how much time they felt the need to open their bowel but were not able to. The physical discomfort score was calculated as the mean of the 4 individual scores. A negative change from baseline value indicates improvement.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL
The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants' daily life during the past 2 weeks.
Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The psychosocial discomfort domain consists of 8 questions related to participants' embarrassment regarding their constipation and effects of constipation on eating habits and appetite.
The psychosocial discomfort score was calculated as the mean of the 8 individual scores. A negative change from baseline value indicates improvement.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Worries and Concerns Domain of PAC-QOL
The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants' daily life during the past 2 weeks.
Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The worries and concerns domain consists of 11 questions related to participants' feelings and concerns about their constipation. The worries and concerns domain score was calculated as the mean of the 11 individual scores. A negative change from baseline value indicates improvement.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Satisfaction Domain of PAC-QOL
The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants' daily life during the past 2 weeks.
Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The satisfaction domain consists of 5 questions related to participants' feelings of satisfaction with their bowel function. The satisfaction domain score was calculated as the mean of the 5 individual scores. A negative change from baseline value indicates improvement.
Measured: Baseline and Weeks 2, 12, 24, 36, and 52
Participant Global Satisfaction
Participants were asked to rate their degree of satisfaction of constipation and abdominal symptoms from the start of study drug dosing to Week 52 (or early termination).
Satisfaction was rated based on the following seven grades:
- Grade 1 = markedly worsened
- Grade 2 = moderately worsened
- Grade 3 = slightly worsened
- Grade 4 = unchanged
- Grade 5 = slightly improved
- Grade 6 = moderately improved
- Grade 7 = markedly improved
Measured: Week 52 or early termination visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2013 (estimated)
- Study start24 Sep 2013
- Primary completion12 Jan 2016
- Study completion12 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Opioid-induced ConstipationStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,246 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01965652
- Sponsor's protocol ID
- 1326V9235
- Status last verified
- Apr 2018
- First submitted
- 15 Oct 2013
- Last updated
- 18 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 34295186Webster 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.
PubMed 32280263Wild 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.
PubMed 32086791
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study to Evaluate the Long-term Safety of Naldemedine for the Treatment of Opioid-induced Constipation in Subjects With Non-malignant Chronic Pain Receiving Opioid Therapy
- ClinicalTrials.gov ID
- NCT01965652
- Acronym / sponsor ID
- 1326V9235
- Conditions
- Opioid-induced Constipation
- Keywords
- Opioid Induced Constipation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,246 participants (actual)
- Lead sponsor
- ShionogiIndustry (pharma, biotech, devices)
- Study start
- 24 Sep 2013 (actual)
- Primary completion
- 12 Jan 2016 (actual)
- Study completion
- 12 Jan 2016 (actual)
- First posted
- 18 Oct 2013 (estimated)
- Results
- Posted 30 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the long-term safety of naldemedine for the treatment of constipation due to opioid therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naldemedine | Experimental | Drug: NaldemedineParticipants received 0.2 mg naldemedine tablets orally once daily for 52 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received matching placebo tablets orally once daily for 52 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects aged 18 to 80 years inclusive at the time of informed consent
- Subjects must have non-malignant chronic pain treated 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 may or may not be on a routine laxative regimen at the time of Screening
Key exclusion criteria (7 listed)
- Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
- Evidence of active medical diseases affecting bowel transit
- History 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaldemedineAlso: S-297995, Symproic®Naldemedine 0.2 mg tablet taken orally once a day | Drug | Naldemedine |
| PlaceboPlacebo tablet taken orally once a day | Drug | Placebo |
Primary outcome
Number of Participants With Adverse Events
Time frame: From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).
A serious adverse event was defined as any adverse event (AE) that resulted in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life threatening, or require hospitalization were considered an SAE when, based upon appropriate medical judgment, they jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. Adverse drug reactions (ADRs) were defined as adverse events that were considered by the investigator to be definitely, probably, or possibly related to study drug. Serious ADRs were defined as serious AEs considered by the investigator to be definitely, probably, or possibly related to study drug.
12 secondary outcomes
Change From Baseline in the Number of Bowel Movements Per Week
Time frame: Baseline and Weeks 12, 24, 36, and 52
Percentage of Participants Meeting Each Criterion of Laxative Use
Time frame: From 28 days prior to screening until the end of the treatment period (total of 56 weeks)
Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the PAC-SYM Stool-symptoms Domain Score
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Physical Discomfort Domain of PAC-QOL
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Worries and Concerns Domain of PAC-QOL
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Change From Baseline in the Satisfaction Domain of PAC-QOL
Time frame: Baseline and Weeks 2, 12, 24, 36, and 52
Participant Global Satisfaction
Time frame: Week 52 or early termination visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34295186Camilleri 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.
- Derived from this study: PubMed 32280263Webster 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.
- Derived from this study: PubMed 32086791Wild 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.
Related trials for Opioid-induced Constipation
RecruitingPhase 4
Prevention of Opioid-induced Constipation in Patients With Advanced Cancer
Constipation, Opioid-Induced
RecruitingObservational study
Risk of Major Adverse Cardiovascular Events for Naldemedine & Other Medications for Opioid Induced Constipation
Opioid-induced Constipation
RecruitingPhase 1/2
Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
Opioid-Induced Constipation (OIC)
Not yet recruitingPhase 3
A Prospective, Multicenter, Randomized, Parallel-controlled, Superiority Trial
OIC
RecruitingObservational study
Naldemedine in Clinical Practice in Cancer Patients With Opioid Induced CONstipation: Clinical Outcomes and Patient Experience
Cancer, Opioid Induced Constipation (OIC)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shionogi Clinical Trials Administrator Clinical Support Help Line study director
Shionogi
186 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Naldemedine in people with Opioid-induced Constipation, run by Shionogi at 186 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 186 sites in United States, United Kingdom, Germany, Australia, Italy and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01965652, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2018.