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

Primary Purpose

Opioid-induced Constipation

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Naldemedine
Sponsored by
Shionogi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid-induced Constipation focused on measuring Opioid Therapy, Non-Malignant Chronic Pain, Opioid-Induced Constipation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Placebo

Naldemedine 0.1 mg

Naldemedine 0.2 mg

Naldemedine 0.4 mg

Arm Description

Participants received placebo orally once daily for 28 days.

Participants received 0.1 mg naldemedine orally once daily for 28 days.

Participants received 0.2 mg naldemedine orally once daily for 28 days.

Participants received 0.4 mg naldemedine orally once daily for 28 days.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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?'
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?'
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 20, 2011
Last Updated
May 31, 2017
Sponsor
Shionogi
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1. Study Identification

Unique Protocol Identification Number
NCT01443403
Brief Title
A Study of Naldemedine (S-297995) for the Treatment of Opioid-Induced Constipation in Adults With Non-Malignant Chronic Pain Receiving Opioid Therapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 17, 2011 (Actual)
Primary Completion Date
August 22, 2012 (Actual)
Study Completion Date
August 22, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shionogi

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-induced Constipation
Keywords
Opioid Therapy, Non-Malignant Chronic Pain, Opioid-Induced Constipation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
244 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo orally once daily for 28 days.
Arm Title
Naldemedine 0.1 mg
Arm Type
Experimental
Arm Description
Participants received 0.1 mg naldemedine orally once daily for 28 days.
Arm Title
Naldemedine 0.2 mg
Arm Type
Experimental
Arm Description
Participants received 0.2 mg naldemedine orally once daily for 28 days.
Arm Title
Naldemedine 0.4 mg
Arm Type
Experimental
Arm Description
Participants received 0.4 mg naldemedine orally once daily for 28 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablets administered orally once a day.
Intervention Type
Drug
Intervention Name(s)
Naldemedine
Other Intervention Name(s)
S 297995, Symproic®
Intervention Description
Naldemedine tablets administered orally once a day.
Primary Outcome Measure Information:
Title
Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
Description
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.
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)
Secondary Outcome Measure Information:
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Spontaneous Bowel Movements Per Week
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Bowel Movements (BMs) Per Week
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Bowel Movements Per Week
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Bowel Movements (CBMs) Per Week
Description
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?'
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Bowel Movements Per Week
Description
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?'
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Spontaneous Bowel Movements Per Week
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Percentage of Participants With an SBM Response in the Last 2 Weeks of the Treatment Period
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Percentage of Participants With an SBM Response at Weeks 1, 2, 3 and 4
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Percentage of Participants With a CSBM Response in the Last 2 Weeks of the Treatment Period
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Percentage of Participants With a CSBM Response at Weeks 1, 2, 3, and 4
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With SBMs
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With SBMs
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With CSBMs
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With CSBMs
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Time to the First Spontaneous Bowel Movement
Description
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.
Time Frame
28 days
Title
Time to the First Complete Spontaneous Bowel Movement
Description
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.
Time Frame
28 days
Title
Percentage of Participants With SBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
Description
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.
Time Frame
4, 8, 12, and 24 hours
Title
Percentage of Participants With CSBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
Description
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.
Time Frame
4, 8, 12, and 24 hours
Title
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
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
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
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week With no Straining
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of SBMs Per Week Without Straining
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of False Start BMs Per Week
Description
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).
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Rescue Use of Laxative Agents Per Week
Description
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).
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Mean Rescue Laxative Use Per Week During the Treatment Period
Description
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).
Time Frame
Weeks 1 to 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Bloating
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Bloating
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Discomfort
Description
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.
Time Frame
Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Title
Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Discomfort
Description
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.
Time Frame
Baseline and Weeks 1, 2, 3, and 4
Title
Subject Global Satisfaction at End of Treatment
Description
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.
Time Frame
Day 29, or at early termination
Title
Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
Description
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.
Time Frame
Day 1 and Day 28 predose and 1, 2, 4, 8, and 24 hours postdose
Title
Time to Maximum Concentration (Tmax) of Naldemedine and Metabolite Nor-S-297995
Description
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.
Time Frame
Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
Title
Area Under the Concentration-time Curve From Hour 0 to the Time Point of the Last Measurable Concentration Within the Dose Interval (AUC0-τ)
Description
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.
Time Frame
Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From first dose of study drug through 28 days after the last dose of study treatment (up to 57 days).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
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
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Shionogi Research Site
City
Sun Lakes
State/Province
Arizona
Country
United States
Facility Name
Shionogi Research Site
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
Shionogi Research Site
City
Anaheim
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Fresno
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Lincoln
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Lomita
State/Province
California
Country
United States
Facility Name
Shionogi Research Site
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Shionogi Research Site
City
Brandon
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Kissimmee
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
New Port Richey
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
North Miami
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Ocala
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
Ormond Beach
State/Province
Florida
Country
United States
Facility Name
Shionogi Research Site
City
Port Orange
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
South Miami
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
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Shionogi Research Site
City
Decatur
State/Province
Georgia
Country
United States
Facility Name
Shionogi Research Site
City
Marietta
State/Province
Georgia
Country
United States
Facility Name
Shionogi Research Site
City
Evansville
State/Province
Indiana
Country
United States
Facility Name
Shionogi Research Site
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
Shionogi Research Site
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Shionogi Research Site
City
Owings Mills
State/Province
Maryland
Country
United States
Facility Name
Shionogi Research Site
City
Watertown
State/Province
Massachusetts
Country
United States
Facility Name
Shionogi Research Site
City
Worcester
State/Province
Massachusetts
Country
United States
Facility Name
Shionogi Research Site
City
Traverse City
State/Province
Michigan
Country
United States
Facility Name
Shionogi Research Site
City
Edina
State/Province
Minnesota
Country
United States
Facility Name
Shionogi Research Site
City
Las Vegas
State/Province
Nevada
Country
United States
Facility Name
Shionogi Research Site
City
Newington
State/Province
New Hampshire
Country
United States
Facility Name
Shionogi Research Site
City
Berlin
State/Province
New Jersey
Country
United States
Facility Name
Shionogi Research Site
City
Willingboro
State/Province
New Jersey
Country
United States
Facility Name
Shionogi Research Site
City
Hartsdale
State/Province
New York
Country
United States
Facility Name
Shionogi Research Site
City
North Syracuse
State/Province
New York
Country
United States
Facility Name
Shionogi Research Site
City
Williamsville
State/Province
New York
Country
United States
Facility Name
Shionogi Research Site
City
Wilmington
State/Province
North Carolina
Country
United States
Facility Name
Shionogi Research Site
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
Shionogi Research Site
City
Canton
State/Province
Ohio
Country
United States
Facility Name
Shionogi Research Site
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Shionogi Research Site
City
Perrysburg
State/Province
Ohio
Country
United States
Facility Name
Shionogi Research Site
City
Eugene
State/Province
Oregon
Country
United States
Facility Name
Shionogi Research Site
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Shionogi Research Site
City
Greer
State/Province
South Carolina
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
Orem
State/Province
Utah
Country
United States
Facility Name
Shionogi Research Site
City
Salt Lake City
State/Province
Utah
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28371937
Citation
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.
Results Reference
result

Learn more about this trial

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

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