Opioid-induced ConstipationPhase 2NCT01443403

A Study of Naldemedine (S-297995) for the Treatment of Opioid-Induced Constipation in Adults With Non-Malignant Chronic Pain Receiving Opioid Therapy

A Phase 2 study testing Naldemedine in people with Opioid-induced Constipation, run by Shionogi at 49 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to determine efficacy and safety of naldemedine for the treatment of opioid-induced constipation in adults with non-malignant chronic pain receiving opioid therapy for ≥ 3 months. Read more about this study

Who is it for?: Ages 18 years and older
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: 244 participants
Where: 49 sitesUnited States
Study dates: 17 Aug 2011to 22 Aug 2012
Phase: Phase 2
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects aged 18 years or older at time of informed consent with non-malignant chronic pain experiencing opioid-induced constipation
Subjects with < 3 spontaneous bowel movements a week and experiencing bowel symptoms
Subjects receiving chronic opioid therapy due to non-malignant pain for ≥ 3 months

Who cannot join

Evidence of clinically significant gastrointestinal disease
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
Severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation

Trial locations and contacts

49 sites in 1 country.

City, postcode or hospital

49 sites in 1 country

United States49 sites

Shionogi Research Site
Anaheim, California
Shionogi Research Site
Atlanta, Georgia
Shionogi Research Site
Austin, Texas
Shionogi Research Site
Berlin, New Jersey
Shionogi Research Site
Brandon, Florida
Shionogi Research Site
Canton, Ohio
Shionogi Research Site
Columbus, Ohio
Shionogi Research Site
Dallas, Texas
Shionogi Research Site
Decatur, Georgia
Shionogi Research Site
Denver, Colorado
Shionogi Research Site
Edina, Minnesota
Shionogi Research Site
Eugene, Oregon
Shionogi Research Site
Evansville, Indiana
Shionogi Research Site
Fresno, California
Shionogi Research Site
Greer, South Carolina
Shionogi Research Site
Hartsdale, New York
Shionogi Research Site
Kissimmee, Florida
Shionogi Research Site
Las Vegas, Nevada
Shionogi Research Site
Lexington, Kentucky
Shionogi Research Site
Lincoln, California
Shionogi Research Site
Little Rock, Arkansas
Shionogi Research Site
Lomita, California
Shionogi Research Site
Marietta, Georgia
Shionogi Research Site
New Port Richey, Florida
Shionogi Research Site
Newington, New Hampshire
Shionogi Research Site
North Miami, Florida
Shionogi Research Site
North Syracuse, New York
Shionogi Research Site
Ocala, Florida
Shionogi Research Site
Orem, Utah
Shionogi Research Site
Orlando, Florida
Shionogi Research Site
Ormond Beach, Florida
Shionogi Research Site
Owings Mills, Maryland
Shionogi Research Site
Perrysburg, Ohio
Shionogi Research Site
Philadelphia, Pennsylvania
Shionogi Research Site
Phoenix, Arizona
Shionogi Research Site
Port Orange, Florida
Shionogi Research Site
Salt Lake City, Utah
Shionogi Research Site
Sarasota, Florida
Shionogi Research Site
Shreveport, Louisiana
Shionogi Research Site
South Miami, Florida
Shionogi Research Site
Sun Lakes, Arizona
Shionogi Research Site
Traverse City, Michigan
Shionogi Research Site
Watertown, Massachusetts
Shionogi Research Site
West Palm Beach, Florida
Shionogi Research Site
Williamsville, New York
Shionogi Research Site
Willingboro, New Jersey
Shionogi Research Site
Wilmington, North Carolina
Shionogi Research Site
Winston-Salem, North Carolina
Shionogi Research Site
Worcester, Massachusetts

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of S-297995 for the Treatment of Opioid-Induced Constipation in Subjects With Non-Malignant Chronic Pain Receiving Opioid Therapy

Conditions: Opioid-induced Constipation
Being tested: Placebo, Naldemedine
Keywords: Opioid Therapy, Non-Malignant Chronic Pain, 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.

PlaceboDrug
Matching placebo tablets administered orally once a day.
NaldemedineDrug
Also called S 297995, Symproic®
Naldemedine tablets administered orally once a day.

Study groups in NCT01443403
Study group	Role	What they receive
Placebo	Placebo comparator	Participants received placebo orally once daily for 28 days. Receives: Drug: Placebo
Naldemedine 0.1 mg	Experimental	Participants received 0.1 mg naldemedine orally once daily for 28 days. Receives: Drug: Naldemedine
Naldemedine 0.2 mg	Experimental	Participants received 0.2 mg naldemedine orally once daily for 28 days. Receives: Drug: Naldemedine
Naldemedine 0.4 mg	Experimental	Participants received 0.4 mg naldemedine orally once daily for 28 days. Receives: Drug: Naldemedine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A spontaneous bowel movement was defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per week during the 2 weeks prior to randomization. The number of SBMs per week in the last 2 weeks of treatment is defined as the average number of SBMs per week recorded in the diary for the 14 days prior to the last dose of study drug.
Measured: Baseline (2 weeks prior to randomization) and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)

Secondary outcomes (35)

Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Spontaneous Bowel Movements Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A spontaneous bowel movement was defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per day during the 2 weeks prior to randomization.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Bowel Movements (BMs) Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A BM was defined as all bowel movements observed irrespective of the use of a laxative agent.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Bowel Movements Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A BM was defined as all bowel movements observed irrespective of the use of a laxative agent.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Bowel Movements (CBMs) Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A complete BM (CBM) was defined as a BM where the participant answered 'Yes' to the following question: 'Did you have a feeling of complete emptying after the bowel movement?'
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Bowel Movements Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A complete BM (CBM) was defined as a BM where the participant answered 'Yes' to the following question: 'Did you have a feeling of complete emptying after the bowel movement?'
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Spontaneous Bowel Movements Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation.
Measured: Baseline and Weeks 1, 2, 3, and 4
Percentage of Participants With an SBM Response in the Last 2 Weeks of the Treatment Period
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
An SBM responder was defined as a participant whose frequency of SBMs within the last 2 weeks of the treatment period was 3 times or more per week and who had an average increase in the frequency of SBMs from baseline of 1 or more per week.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Percentage of Participants With an SBM Response at Weeks 1, 2, 3 and 4
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
An SBM responder was defined as any participant whose frequency of SBM per week during the treatment period was 3 times or more per week, and who had an average increase from baseline of 1 or more per week.
Measured: Baseline and Weeks 1, 2, 3, and 4
Percentage of Participants With a CSBM Response in the Last 2 Weeks of the Treatment Period
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A CSBM responder was defined as a participant whose frequency of CSBMs within the last 2 weeks of the treatment period was 3 times or more per week and who had an average increase in the frequency of CSBMs from baseline of 1 or more per week.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Percentage of Participants With a CSBM Response at Weeks 1, 2, 3, and 4
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A CSBM responder was defined as a participant whose frequency of CSBMs during the treatment period was 3 times or more per week and who had an average increase in the frequency of CSBMs from baseline of 1 or more per week.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With SBMs
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
An SBM is defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With SBMs
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
An SBM is defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With CSBMs
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With CSBMs
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A CSBM was defined as a spontaneous BM which was accompanied by the feeling of complete evacuation.
Measured: Baseline and Weeks 1, 2, 3, and 4
Time to the First Spontaneous Bowel Movement
Time to the first SBM was defined as the time to the first SBM after the initial administration of study drug. Participants who withdrew from the study before an SBM was observed or had no SBM during the treatment period were treated as censored.
Measured: 28 days
Time to the First Complete Spontaneous Bowel Movement
Time to the first CSBM was defined as the time to the first CSBM after the initial administration of study drug. Participants who withdrew from the study before a CSBM was observed or had no CSBM during the treatment period were treated as censored.
Measured: 28 days
Percentage of Participants With SBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
The percentage of participants who experienced at least one SBM within 4, 8, 12, and 24 hours after the initial administration of study drug and before the second administration.
Measured: 4, 8, 12, and 24 hours
Percentage of Participants With CSBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
The percentage of participants who experienced at least one CSBM within 4, 8, 12, and 24 hours after the initial administration of study drug and before the second administration.
Measured: 4, 8, 12, and 24 hours
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week Rated as 3 or 4 on the Bristol Stool Scale
Consistency of BMs was measured using the Bristol Stool Scale, according to the following: 1 = separate hard lumps like nuts; 2 = sausage shaped but lumpy; 3 = like a sausage, but with cracks on its surface; 4 = like a sausage or a snake, smooth and soft; 5 = soft blobs and with clear-cut edges; 6 = floppy pieces with ragged edges/mushy stool; 7 = watery, no solid pieces, entirely liquid.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in Number of SBMs Rated as 3 or 4 on the Bristol Stool Scale Per Week
Consistency of BMs was measured using the Bristol Stool Scale, according to the following: 1 = separate hard lumps like nuts; 2 = sausage shaped but lumpy; 3 = like a sausage, but with cracks on its surface; 4 = like a sausage or a snake, smooth and soft; 5 = soft blobs and with clear-cut edges; 6 = floppy pieces with ragged edges/mushy stool; 7 = watery, no solid pieces, entirely liquid.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week With no Straining
Straining during BMs was graded using the following scale: 0 = No straining; 1 = Mild straining; 2 = Moderate; 3 = Severe; 4 = Very Severe. A BM without straining was defined as a BM with a straining score of 0 or 1.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of SBMs Per Week Without Straining
Straining during BMs was graded using the following scale: 0 = No straining; 1 = Mild straining; 2 = Moderate; 3 = Severe; 4 = Very Severe. A BM without straining is defined as a BM with a straining score of 0 or 1.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of False Start BMs Per Week
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation.
A false start was defined as any attempted, but unsuccessful bowel movement (no solid or liquid fecal material was excreted).
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to the Last 2 Weeks of the Treatment Period in Rescue Use of Laxative Agents Per Week
Participants were asked how many doses of rescue laxative medication they had taken within the past 24 hours as part of the Bowel Movement and Constipation Assessment Diary (BMCA).
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Mean Rescue Laxative Use Per Week During the Treatment Period
Participants were asked how many doses of rescue laxative medication they had taken within the past 24 hours as part of the Bowel Movement and Constipation Assessment Diary (BMCA).
Measured: Weeks 1 to 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Bloating
Participants were asked to rate their abdominal bloating for the past 24 hours on a scale of 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Bloating
Participants were asked to rate their abdominal bloating for the past 24 hours on a scale of 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe.
Measured: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Discomfort
Participants were asked to rate their abdominal discomfort for the past 24 hours on a scale from 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe.
Measured: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Discomfort
Participants were asked to rate their abdominal discomfort for the past 24 hours on a scale from 0 to 4, where 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe.
Measured: Baseline and Weeks 1, 2, 3, and 4
Subject Global Satisfaction at End of Treatment
On day 29 (or at early termination), participants were asked about their degree of satisfaction with constipation and abdominal symptoms from the start of study drug dosing to Day 28 (or early termination visit). The grades were as follows: 1, markedly worsened; 2, moderately worsened; 3, slightly worsened; 4, unchanged; 5, slightly improved; 6, moderately improved; and 7, markedly improved.
Measured: Day 29, or at early termination
Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
Pharmacokinetic blood samples for naldemedine (S-297995) and its metabolite, Nor-S-297995, were collected from a subset of participants at selected study sites on Day 1 and in a further subset on Day 28.
Measured: Day 1 and Day 28 predose and 1, 2, 4, 8, and 24 hours postdose
Time to Maximum Concentration (Tmax) of Naldemedine and Metabolite Nor-S-297995
Pharmacokinetic blood samples for naldemedine (S-297995) and its metabolite, Nor-S-297995, were collected from a subset of participants at selected study sites on Day 1 and in a further subset on Day 28.
Measured: Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
Area Under the Concentration-time Curve From Hour 0 to the Time Point of the Last Measurable Concentration Within the Dose Interval (AUC0-τ)
Pharmacokinetic blood samples for naldemedine (S-297995) and its metabolite, Nor-S-297995, were collected from a subset of participants at selected study sites on Day 1 and in a further subset on Day 28.
Measured: Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Treatment-emergent adverse events (TEAEs) were adverse events that occurred after the first dose of study drug.
Treatment-related TEAEs were defined as TEAEs that were considered by the Investigator to be definitely, probably, or possibly related to study drug.
Measured: From first dose of study drug through 28 days after the last dose of study treatment (up to 57 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Aug 201122 Aug 2012

First posted29 Sep 2011 (estimated)
Study start17 Aug 2011
Primary completion22 Aug 2012
Study completion22 Aug 2012

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 (1)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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 244 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01443403
Sponsor's protocol ID: 1107V9221
Status last verified: May 2017
First submitted: 20 Sep 2011
Last updated: 26 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Webster LR, Yamada T, Arjona Ferreira JC. A Phase 2b, Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain. Pain Med. 2017 Dec 1;18(12):2350-2360. doi: 10.1093/pm/pnw325.
PubMed 28371937

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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)

All Opioid-induced Constipation trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of S-297995 for the Treatment of Opioid-Induced Constipation in Subjects With Non-Malignant Chronic Pain Receiving Opioid Therapy
ClinicalTrials.gov ID: NCT01443403
Acronym / sponsor ID: 1107V9221
Conditions: Opioid-induced Constipation
Keywords: Opioid Therapy, Non-Malignant Chronic Pain, Opioid-Induced Constipation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 244 participants (actual)
Lead sponsor: ShionogiIndustry (pharma, biotech, devices)
Study start: 17 Aug 2011 (actual)
Primary completion: 22 Aug 2012 (actual)
Study completion: 22 Aug 2012 (actual)
First posted: 29 Sep 2011 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboParticipants received placebo orally once daily for 28 days.
Naldemedine 0.1 mg	Experimental	Drug: NaldemedineParticipants received 0.1 mg naldemedine orally once daily for 28 days.
Naldemedine 0.2 mg	Experimental	Drug: NaldemedineParticipants received 0.2 mg naldemedine orally once daily for 28 days.
Naldemedine 0.4 mg	Experimental	Drug: NaldemedineParticipants received 0.4 mg naldemedine orally once daily for 28 days.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Subjects aged 18 years or older at time of informed consent with non-malignant chronic pain experiencing opioid-induced constipation
Subjects with < 3 spontaneous bowel movements a week and experiencing bowel symptoms
Subjects receiving chronic opioid therapy due to non-malignant pain for ≥ 3 months

Key exclusion criteria (3 listed)

Evidence of clinically significant gastrointestinal disease
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
Severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation

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
PlaceboMatching placebo tablets administered orally once a day.	Drug	Placebo
NaldemedineAlso: S 297995, Symproic®Naldemedine tablets administered orally once a day.	Drug	Naldemedine 0.1 mg, Naldemedine 0.2 mg, Naldemedine 0.4 mg

Primary outcome

Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
Time frame: Baseline (2 weeks prior to randomization) and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Participants completed a daily Bowel Movement and Constipation Assessment Diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement unassisted by rescue medication (laxative or enema) taken within the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per week during the 2 weeks prior to randomization. The number of SBMs per week in the last 2 weeks of treatment is defined as the average number of SBMs per week recorded in the diary for the 14 days prior to the last dose of study drug.

35 secondary outcomes

Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Spontaneous Bowel Movements Per Week
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Bowel Movements (BMs) Per Week
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Bowel Movements Per Week
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Bowel Movements (CBMs) Per Week
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Bowel Movements Per Week
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Spontaneous Bowel Movements Per Week
Time frame: Baseline and Weeks 1, 2, 3, and 4
Percentage of Participants With an SBM Response in the Last 2 Weeks of the Treatment Period
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Percentage of Participants With an SBM Response at Weeks 1, 2, 3 and 4
Time frame: Baseline and Weeks 1, 2, 3, and 4
Percentage of Participants With a CSBM Response in the Last 2 Weeks of the Treatment Period
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Percentage of Participants With a CSBM Response at Weeks 1, 2, 3, and 4
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With SBMs
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With SBMs
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With CSBMs
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With CSBMs
Time frame: Baseline and Weeks 1, 2, 3, and 4
Time to the First Spontaneous Bowel Movement
Time frame: 28 days
Time to the First Complete Spontaneous Bowel Movement
Time frame: 28 days
Percentage of Participants With SBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
Time frame: 4, 8, 12, and 24 hours
Percentage of Participants With CSBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
Time frame: 4, 8, 12, and 24 hours
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week Rated as 3 or 4 on the Bristol Stool Scale
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in Number of SBMs Rated as 3 or 4 on the Bristol Stool Scale Per Week
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week With no Straining
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of SBMs Per Week Without Straining
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of False Start BMs Per Week
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to the Last 2 Weeks of the Treatment Period in Rescue Use of Laxative Agents Per Week
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Mean Rescue Laxative Use Per Week During the Treatment Period
Time frame: Weeks 1 to 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Bloating
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Bloating
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Discomfort
Time frame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Discomfort
Time frame: Baseline and Weeks 1, 2, 3, and 4
Subject Global Satisfaction at End of Treatment
Time frame: Day 29, or at early termination
Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
Time frame: Day 1 and Day 28 predose and 1, 2, 4, 8, and 24 hours postdose
Time to Maximum Concentration (Tmax) of Naldemedine and Metabolite Nor-S-297995
Time frame: Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
Area Under the Concentration-time Curve From Hour 0 to the Time Point of the Last Measurable Concentration Within the Dose Interval (AUC0-τ)
Time frame: Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug through 28 days after the last dose of study treatment (up to 57 days).

Results and safety

Results posted to the registry on 30 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	61	55
Naldemedine 0.1 mg	61	55
Naldemedine 0.2 mg	61	54
Naldemedine 0.4 mg	61	52

Primary outcome: Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week

Time frame: Baseline (2 weeks prior to randomization) and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period). Least squares mean (Standard Error). Unit: spontaneous bowel movements per week

Measure	Placebo n = 61	Naldemedine 0.1 mg n = 61	Naldemedine 0.2 mg n = 59	Naldemedine 0.4 mg n = 57
Value	1.42 (0.422)	1.98 (0.422)	3.37 (0.429)	3.64 (0.437)

Placebo vs Naldemedine 0.4 mg: LS Mean Difference: 2.22 (95% CI 1.02 to 3.41), p = 0.0003, ANCOVA
Placebo vs Naldemedine 0.2 mg: LS Mean Difference: 1.95 (95% CI 0.76 to 3.14), p = 0.0014, ANCOVA
Placebo vs Naldemedine 0.1 mg: LS Mean Difference: 0.56 (95% CI -0.62 to 1.74), p = 0.3504, ANCOVA

Population analysed: Modified intention-to-treat population

35 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study drug through 28 days after the last dose of study treatment (up to 57 days).. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 61 (0%)	19 of 61 (31.1%)	Not reported
Naldemedine 0.1 mg	2 of 61 (3.3%)	15 of 61 (24.6%)	Not reported
Naldemedine 0.2 mg	0 of 60 (0%)	19 of 60 (31.7%)	Not reported
Naldemedine 0.4 mg	1 of 61 (1.6%)	28 of 61 (45.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28371937Webster LR, Yamada T, Arjona Ferreira JC. A Phase 2b, Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain. Pain Med. 2017 Dec 1;18(12):2350-2360. doi: 10.1093/pm/pnw325.

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

49 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Naldemedine in people with Opioid-induced Constipation, run by Shionogi at 49 sites in United States.

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 3 inclusion and 3 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 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week (time frame: Baseline (2 weeks prior to randomization) and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)). 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 NCT01443403, which also lists 1 linked publication.

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 26 Jun 2017.