Phase 2
N=244
A Study of Naldemedine (S-297995) for the Treatment of Opioid-Induced Constipation in Adults With Non-Malignant Chronic Pain Receiving Opioid Therapy
Opioid-induced Constipation
Bottom Line
View on ClinicalTrials.gov: NCT01443403 ↗Enrolled (actual)
244
Serious AEs
1.2%
Results posted
May 2017
Primary outcome: Primary: Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week — 1.42; 1.98; 3.37; 3.64 spontaneous bowel movements per week — p=0.0003
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); Naldemedine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Shionogi
- Primary completion
- Aug 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week |
1.42; 1.98; 3.37; 3.64 | 0.0003 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Spontaneous Bowel Movements Per Week |
1.61; 2.21; 4.05; 4.52; 1.53; 2.06 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Bowel Movements (BMs) Per Week |
1.43; 2.07; 3.35; 3.36 | 0.0008 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Bowel Movements Per Week |
1.67; 2.27; 4.25; 4.60; 1.65; 1.97 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Bowel Movements (CBMs) Per Week |
1.08; 1.58; 2.71; 2.41 | 0.0065 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Bowel Movements Per Week |
0.73; 1.38; 2.88; 3.14; 1.07; 1.54 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week |
0.99; 1.49; 2.69; 2.44 | 0.0039 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Spontaneous Bowel Movements Per Week |
0.71; 1.31; 2.63; 2.99; 1.09; 1.41 | — |
| SECONDARY Percentage of Participants With an SBM Response in the Last 2 Weeks of the Treatment Period |
39.3; 52.5; 71.2; 66.7 | 0.0030 sig |
| SECONDARY Percentage of Participants With an SBM Response at Weeks 1, 2, 3 and 4 |
45.9; 62.3; 72.9; 70.2; 45.9; 55.7 | — |
| SECONDARY Percentage of Participants With a CSBM Response in the Last 2 Weeks of the Treatment Period |
21.3; 29.5; 45.8; 45.6 | 0.0050 sig |
| SECONDARY Percentage of Participants With a CSBM Response at Weeks 1, 2, 3, and 4 |
21.3; 31.1; 42.4; 50.9; 23.0; 29.5 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With SBMs |
0.88; 1.46; 2.10; 2.42 | <0.0001 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With SBMs |
1.12; 1.62; 2.35; 2.38; 1.03; 1.56 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With CSBMs |
0.83; 1.25; 1.93; 2.02 | 0.0001 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With CSBMs |
0.65; 1.17; 1.74; 2.14; 0.90; 1.18 | — |
| SECONDARY Time to the First Spontaneous Bowel Movement |
49.57; 28.15; 11.08; 21.33 | 0.0004 sig |
| SECONDARY Time to the First Complete Spontaneous Bowel Movement |
223.92; 82.50; 44.83; 32.93 | <0.0001 sig |
| SECONDARY Percentage of Participants With SBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug |
8.2; 18.0; 35.6; 31.6; 16.4; 29.5 | — |
| SECONDARY Percentage of Participants With CSBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug |
1.6; 11.5; 18.6; 12.3; 6.6; 16.4 | — |
| SECONDARY 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 |
0.54; 1.08; 2.05; 1.87 | 0.0003 sig |
| SECONDARY 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 |
0.60; 0.97; 2.16; 1.76; 0.62; 1.19 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week With no Straining |
0.85; 1.54; 2.92; 3.21 | <0.0001 sig |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of SBMs Per Week Without Straining |
0.97; 1.42; 3.23; 3.46; 0.97; 1.43 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of False Start BMs Per Week |
-2.71; -3.06; -3.75; -2.80 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Rescue Use of Laxative Agents Per Week |
0.94; -0.47; 0.15; -1.24 | 0.0272 sig |
| SECONDARY Mean Rescue Laxative Use Per Week During the Treatment Period |
2.9; 0.9; 2.9; 1.8 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Bloating |
-0.40; -0.46; -0.54; -0.57 | 0.2126 |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Bloating |
-0.20; -0.30; -0.34; -0.48; -0.36; -0.45 | — |
| SECONDARY Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Discomfort |
-0.42; -0.51; -0.50; -0.42 | 0.9826 |
| SECONDARY Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Discomfort |
-0.22; -0.35; -0.24; -0.23; -0.27; -0.48 | — |
| SECONDARY Subject Global Satisfaction at End of Treatment |
1; 0; 0; 1; 2; 2 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995 |
0.987; 1.89; 3.67; 1.15; 2.00; 4.03 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of Naldemedine and Metabolite Nor-S-297995 |
1.00; 1.03; 1.03; 1.03; 1.00; 1.00 | — |
| SECONDARY Area Under the Concentration-time Curve From Hour 0 to the Time Point of the Last Measurable Concentration Within the Dose Interval (AUC0-τ) |
8.491; 15.95; 30.58; 9.677; 16.94; 31.72 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
31; 25; 30; 34; 10; 10 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT01443403). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.