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Trial record 1 of 1 for:    NCT01122030
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Study to Evaluate the Safety and Efficacy of Naldemedine (S-297995) for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01122030
Recruitment Status : Completed
First Posted : May 12, 2010
Results First Posted : May 30, 2017
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Opioid Induced Bowel Dysfunction
Interventions Drug: Naldemedine
Drug: Placebo
Enrollment 72
Recruitment Details The study was conducted at a single study center in the United States.
Pre-assignment Details Participants were randomized to naldemedine or placebo, screened for 13 days (Days 1-13), and admitted to the clinic on Day 14 for pre-admission assessments. Six cohorts were sequentially enrolled from Cohort 1 (0.1 mg) to Cohort 2 (0.3 mg), Cohort 3 (1 mg), and Cohort 4 (3 mg), and subsequent de-escalation in Cohorts 5 (0.03 mg) and 6 (0.01 mg).
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions. Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions. Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions. Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions. Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions. Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions. Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Period Title: Overall Study
Started 18 9 9 9 9 9 9
Received Treatment 18 9 9 9 9 9 9
Completed 18 9 9 9 9 9 9
Not Completed 0 0 0 0 0 0 0
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg Total
Hide Arm/Group Description Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions. Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions. Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions. Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions. Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions. Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions. Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions. Total of all reporting groups
Overall Number of Baseline Participants 18 9 9 9 9 9 9 72
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants 72 participants
46.7  (8.55) 41.4  (12.99) 45.2  (13.13) 45.6  (6.02) 39.7  (10.64) 36.6  (10.19) 44.8  (9.09) 43.3  (10.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants 72 participants
Female
7
  38.9%
7
  77.8%
7
  77.8%
5
  55.6%
6
  66.7%
4
  44.4%
2
  22.2%
38
  52.8%
Male
11
  61.1%
2
  22.2%
2
  22.2%
4
  44.4%
3
  33.3%
5
  55.6%
7
  77.8%
34
  47.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants 72 participants
Hispanic or Latino
2
  11.1%
1
  11.1%
1
  11.1%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
5
   6.9%
Not Hispanic or Latino
16
  88.9%
8
  88.9%
8
  88.9%
9
 100.0%
8
  88.9%
9
 100.0%
9
 100.0%
67
  93.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants 72 participants
American Indian or Alaska Native
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
   1.4%
White
18
 100.0%
8
  88.9%
9
 100.0%
9
 100.0%
8
  88.9%
9
 100.0%
9
 100.0%
70
  97.2%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description

Severity of adverse events (AEs) was graded according to the following definitions:

  • Mild: The subject experiences awareness of symptoms but these are easily tolerated or managed without specific treatment
  • Moderate: The subject experiences discomfort enough to cause interference with usual activity, and/or the condition requires specific treatment
  • Severe: The subject is incapacitated with inability to work or do usual activity, and/or the event requires significant treatment measures.

The relationship of the event to the study drug was determined by the investigator.

A serious adverse event (SAE) is defined as any AE occurring at any dose 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.

Time Frame From the first dose of study drug on Day 15 up to Day 24.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug (safety population).
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Measure Type: Number
Unit of Measure: participants
Any adverse event 9 6 6 5 9 9 9
Mild adverse events 9 6 6 4 6 5 1
Moderate adverse events 0 0 0 1 3 3 2
Severe adverse events 0 0 0 0 0 1 6
Treatment-related adverse events 6 5 3 1 9 8 9
Deaths 0 0 0 0 0 0 0
Serious adverse events 0 0 0 0 0 0 0
Adverse events leading to discontinuation 0 0 0 0 0 0 0
2.Secondary Outcome
Title Change From Baseline to 24 Hours Post-dose in Number of Spontaneous Bowel Movements (SBMs) Per Day
Hide Description

Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used in the 24 hours preceding the bowel movement.

Baseline was defined as the average number of SBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15).

Time Frame Baseline (Day 1 to Day 15) and Day 15 to 16 (0 to 24 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug and had at least 1 post-dose efficacy assessment completed (intent-to-treat population). Last observation carried forward (LOCF) imputation was used.
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: spontaneous bowel movements / day
Baseline 0.15  (0.13) 0.20  (0.14) 0.24  (0.09) 0.13  (0.13) 0.17  (0.12) 0.13  (0.09) 0.23  (0.11)
24 hours post-dose 0.44  (0.51) 0.11  (0.33) 0.67  (0.71) 0.56  (0.73) 2.00  (1.32) 3.89  (3.06) 5.00  (2.12)
Change from Baseline to 24 hours post-dose 0.29  (0.48) -0.09  (0.41) 0.42  (0.72) 0.43  (0.68) 1.83  (1.34) 3.76  (3.06) 4.77  (2.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0767
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8727
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6373
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
3.Secondary Outcome
Title Change From Baseline to 48 Hours Post-dose in the Number of SBMs Per Day
Hide Description Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used in the 24 hours preceding the bowel movement. Baseline was defined as the average number of SBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15). Forty-eight hours post-dose was defined as the average number of SBMs per day from 0 to 48 hours post-dose.
Time Frame Baseline (Day 1 to Day 15) and Day 15 to Day 17 (0 to 48 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: Spontaneous bowel movements / day
Baseline 0.15  (0.13) 0.20  (0.14) 0.24  (0.09) 0.13  (0.13) 0.17  (0.12) 0.13  (0.09) 0.23  (0.11)
48 hours post-dose 0.36  (0.33) 0.44  (0.39) 0.67  (0.61) 0.39  (0.49) 1.06  (0.68) 2.28  (1.80) 2.67  (1.03)
Change from Baseline to 48 hours post-dose 0.21  (0.32) 0.24  (0.39) 0.42  (0.65) 0.26  (0.45) 0.88  (0.68) 2.15  (1.81) 2.44  (1.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8982
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4946
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9301
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0047
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of SBMs as a covariate.
4.Secondary Outcome
Title Change From Baseline to 24 Hours Post-dose in Number of Bowel Movements (BM) Per Day
Hide Description Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. Baseline was defined as the average number of BMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15).
Time Frame Baseline and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: bowel movements / day
Baseline 0.35  (0.18) 0.34  (0.10) 0.41  (0.22) 0.35  (0.17) 0.33  (0.12) 0.29  (0.09) 0.38  (0.19)
24 hours post-dose 0.50  (0.62) 0.11  (0.33) 0.67  (0.71) 0.56  (0.73) 2.00  (1.32) 3.89  (3.06) 5.00  (2.12)
Change from Baseline to 24 hours post-dose 0.15  (0.65) -0.23  (0.36) 0.25  (0.75) 0.21  (0.76) 1.67  (1.35) 3.60  (3.10) 4.62  (2.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1334
Comments [Not Specified]
Method ANCOVA
Comments P-value is from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3320
Comments [Not Specified]
Method ANCOVA
Comments P-value is from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9371
Comments [Not Specified]
Method ANCOVA
Comments P-value is from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments P-value is from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-value is from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-value is from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
5.Secondary Outcome
Title Change From Baseline to 48 Hours Post-dose in Number of Bowel Movements Per Day
Hide Description Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. Baseline was defined as the average number of BMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15). Forty-eight hours post-dose was defined as the average number of BMs per day from 0 to 48 hours post-dose.
Time Frame Baseline and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: bowel movements / day
Baseline 0.35  (0.18) 0.34  (0.10) 0.41  (0.22) 0.35  (0.17) 0.33  (0.12) 0.29  (0.09) 0.38  (0.19)
48 hours post-dose 0.50  (0.51) 0.61  (0.49) 0.72  (0.71) 0.56  (0.46) 1.06  (0.68) 2.28  (1.80) 2.67  (1.03)
Change from baseline to 48 hours post-dose 0.15  (0.53) 0.27  (0.51) 0.31  (0.67) 0.21  (0.52) 0.72  (0.70) 1.99  (1.82) 2.29  (0.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7978
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7143
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7531
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0283
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of BMs as a covariate.
6.Secondary Outcome
Title Change From Baseline to 24 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
Hide Description

Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A complete spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used and the bowel movement resulted in a sensation of complete evacuation (based on the question of “having a feeling of complete emptying after the bowel movement”).

Baseline was defined as the average number of CSBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15).

Time Frame Baseline and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: complete spontaneous bowel movements/day
Baseline 0.03  (0.06) 0.07  (0.09) 0.07  (0.08) 0.06  (0.10) 0.01  (0.03) 0.03  (0.04) 0.10  (0.07)
24 hours post-dose 0.06  (0.24) 0.00  (0.00) 0.11  (0.33) 0.22  (0.44) 0.11  (0.33) 2.44  (2.55) 3.00  (3.20)
Change from Baseline to 24 hours post-dose 0.02  (0.25) -0.07  (0.09) 0.04  (0.29) 0.16  (0.44) 0.10  (0.34) 2.42  (2.55) 2.90  (3.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6269
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7456
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1968
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8708
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
7.Secondary Outcome
Title Change From Baseline to 48 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
Hide Description

Participants completed a bowel function assessment daily diary to record information about bowel movements and constipation. A complete spontaneous bowel movement was defined as a bowel movement where no laxative or enema was used and the bowel movement resulted in a sensation of complete evacuation (based on the question of “having a feeling of complete emptying after the bowel movement”).

Baseline was defined as the average number of CSBMs per day during the 2 weeks prior to receiving study drug (Day 1 to Day 15). Forty-eight hours post-dose was defined as the average number of CSBMs per day from 0 to 48 hours post-dose.

Time Frame Baseline and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: complete spontaneous bowel movements/day
Baseline 0.03  (0.06) 0.07  (0.09) 0.07  (0.08) 0.06  (0.10) 0.01  (0.03) 0.03  (0.04) 0.10  (0.07)
48 hours post-dose 0.08  (0.19) 0.17  (0.25) 0.17  (0.25) 0.17  (0.35) 0.06  (0.17) 1.39  (1.34) 1.61  (1.52)
Change from baseline to 48 hours post-dose 0.05  (0.16) 0.10  (0.18) 0.10  (0.25) 0.10  (0.34) 0.04  (0.17) 1.36  (1.34) 1.51  (1.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6131
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9293
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7990
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7674
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method ANCOVA
Comments P-values are from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CSBMs as a covariate.
8.Secondary Outcome
Title Time to First Spontaneous Bowel Movement
Hide Description The time to first SBM during the Study Drug Administration Period was summarized using Kaplan-Meier estimates. Each participant’s first SBM was counted as an event and the time to first SBM after dosing was calculated from the date and time of first dosing until the date and time of first SBM. Participants who dropped out or were lost to follow-up before the first SBM were censored.
Time Frame From first dose on Day 15 through Day 17
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Median (95% Confidence Interval)
Unit of Measure: hours
27.2 [1] 
(12.4 to NA)
37.0 [1] 
(25.8 to NA)
13.9 [1] 
(8.2 to NA)
NA [1] 
(3.3 to NA)
4.7
(2.8 to 6.2)
1.4
(1.0 to 2.3)
0.7
(0.6 to 0.8)
[1]
Could not be estimated due to the low number of events
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7434
Comments [Not Specified]
Method Log Rank
Comments P-values were obtained from the log-rank test stratified by Gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.42 to 3.92
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4449
Comments [Not Specified]
Method Log Rank
Comments P-values were obtained from the log-rank test stratified by Gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.54
Confidence Interval (2-Sided) 95%
0.54 to 4.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8129
Comments [Not Specified]
Method Log Rank
Comments P-values were obtained from the log-rank test stratified by Gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.27 to 2.72
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Log Rank
Comments P-values were obtained from the log-rank test stratified by Gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 7.52
Confidence Interval (2-Sided) 95%
2.29 to 24.72
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments P-values were obtained from the log-rank test stratified by Gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 9.93
Confidence Interval (2-Sided) 95%
3.09 to 31.89
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments P-values were obtained from the log-rank test stratified by Gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 202272814.
Estimation Comments Hazard Ratio is infinite due to small range of observed times in 3 mg group that has no overlap with the Placebo group.
9.Secondary Outcome
Title Time to First Bowel Movement
Hide Description The time to first BM during the Study Drug Administration Period was summarized using Kaplan-Meier estimates. Each participant’s first BM was counted as an event and the time to first BM after dosing was calculated from the date and time of first dosing until the date and time of first BM. Participants who dropped out or were lost to follow-up before the first BM were censored.
Time Frame From first dose on Day 15 through Day 17
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Median (95% Confidence Interval)
Unit of Measure: hours
27.2 [1] 
(12.4 to NA)
28.4
(25.8 to 43.0)
13.9 [1] 
(8.2 to NA)
25.1
(3.3 to 57.3)
4.7
(2.8 to 6.2)
1.4
(1.0 to 2.3)
0.7
(0.6 to 0.8)
[1]
Could not be estimated due to the low number of events
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4923
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
0.53 to 4.28
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5479
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
0.52 to 4.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5060
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.56 to 3.67
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 7.36
Confidence Interval (2-Sided) 95%
2.27 to 23.90
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 9.54
Confidence Interval (2-Sided) 95%
3.00 to 30.35
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 192233779
Estimation Comments Hazard Ratio is infinite due to small range of observed times in 3 mg group that has no overlap with the Placebo group.
10.Secondary Outcome
Title Time to First Complete Spontaneous Bowel Movement
Hide Description The time to first CSBM during the Study Drug Administration Period was summarized using Kaplan-Meier estimates. Each participant’s first CSBM was counted as an event and the time to first CSBM after dosing was calculated from the date and time of first dosing until the date and time of first CSBM. Participants who dropped out or were lost to follow-up before the first CSBM were censored.
Time Frame From first dose on Day 15 through Day 17
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Median (95% Confidence Interval)
Unit of Measure: hours
NA [1] 
(NA to NA)
NA [1] 
(37.0 to NA)
NA [1] 
(37.7 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
1.7
(1.3 to 2.3)
0.8
(0.6 to 25.8)
[1]
Could not be estimated due to the low number of events
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1523
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.45
Confidence Interval (2-Sided) 95%
0.62 to 19.35
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0856
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.55
Confidence Interval (2-Sided) 95%
0.76 to 27.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5284
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
0.30 to 10.98
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8594
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.09 to 8.66
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 59.34
Confidence Interval (2-Sided) 95%
6.55 to 537.38
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Log Rank
Comments P-values are from the log rank test stratified by gender.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 10.99
Confidence Interval (2-Sided) 95%
2.30 to 52.57
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Straining During Bowel Movements
Hide Description

Straining during BMs was graded using the following scale: 0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe.

Baseline was defined as the average straining score of all BMs prior to receiving study drug (Day 1 to Day 15). The straining score at 24 and 48 hours post-dose was calculated as the average straining score from all bowel movements from 0 to 24 and 0 to 48 hours post-dose, respectively.

Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with available data at each time point
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants
2.2  (0.71) 2.0  (0.78) 2.2  (0.68) 1.9  (0.90) 2.0  (1.08) 2.5  (0.97) 1.7  (0.99)
Change from Baseline to 24 hours post-dose Number Analyzed 8 participants 1 participants 5 participants 4 participants 8 participants 9 participants 9 participants
0.8  (0.76) -0.8 [1]   (NA) -0.2  (0.88) -0.7  (0.43) -0.1  (0.89) -0.5  (1.37) -0.9  (1.64)
Change from Baseline to 48 hours post-dose Number Analyzed 6 participants 7 participants 4 participants 4 participants 1 participants 3 participants 3 participants
0.5  (0.87) 0.2  (0.74) 0.4  (0.80) -0.6  (0.67) 0.1 [1]   (NA) -0.4  (0.42) -1.4  (1.40)
[1]
Standard deviation cannot be calculated when n=1
12.Secondary Outcome
Title Change From Baseline to 24 Hours Post-dose in Number of Complete Bowel Movements Per Day
Hide Description A complete bowel movement (CBM) was defined as a bowel movement that resulted in a sensation of complete evacuation based on the question “Did you have a feeling of complete emptying after the bowel movement?” Baseline was defined as the average number of CBMs per day prior to receiving study drug (Day 1 to Day 15).
Time Frame Baseline and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: complete bowel movements / day
Baseline 0.13  (0.16) 0.13  (0.14) 0.11  (0.09) 0.14  (0.12) 0.04  (0.06) 0.12  (0.15) 0.19  (0.15)
24 hours post-dose 0.06  (0.24) 0.00  (0.00) 0.11  (0.33) 0.22  (0.44) 0.11  (0.33) 2.44  (2.55) 3.00  (3.20)
Change from baseline to 24 hours post-dose -0.07  (0.20) -0.13  (0.14) 0.01  (0.31) 0.09  (0.45) 0.07  (0.35) 2.32  (2.61) 2.81  (3.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5054
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9688
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6963
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9599
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
13.Secondary Outcome
Title Change From Baseline to 48 Hours Post-dose in Number of Complete Bowel Movements Per Day
Hide Description A complete bowel movement (CBM) was defined as a bowel movement that resulted in a sensation of complete evacuation based on the question “Did you have a feeling of complete emptying after the bowel movement?” Baseline was defined as the average number of CBMs per day prior to receiving study drug (Day 1 to 15). Forty-eight hours post-dose was calculated as the average number of CBMs per day from 0 to 48 hours post-dose.
Time Frame Baseline and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: complete bowel movements / day
Baseline 0.13  (0.16) 0.13  (0.14) 0.11  (0.09) 0.14  (0.12) 0.04  (0.06) 0.12  (0.15) 0.19  (0.15)
48 hours post-dose 0.08  (0.19) 0.17  (0.25) 0.17  (0.25) 0.22  (0.36) 0.06  (0.17) 1.39  (1.34) 1.61  (1.52)
Change from Baseline to 48 hours post-dose -0.04  (0.17) 0.04  (0.15) 0.06  (0.28) 0.09  (0.38) 0.01  (0.19) 1.27  (1.38) 1.42  (1.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.01 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3441
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.03 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7159
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7342
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8714
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 1 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pooled Placebo, Naldemedine 3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments P-values were obtained from a non-parametric rank ANCOVA model with effects for dose group and gender, and baseline number of CBMs as a covariate.
14.Secondary Outcome
Title Change From Baseline in Abdominal Bloating
Hide Description

Participants were asked to rate their abdominal bloating for the past 24 hours using the following scale:

0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. Baseline was defined as the average abdominal bloating score prior to receiving study drug (Day 1 to Day 15). Abdominal bloating at 24 hours and 48 hours post-dose was calculated as the mean score from 0 to 24 and 0 to 48 hours post-dose respectively.

Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with available data at each time point.
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants
2.0  (0.65) 1.4  (0.95) 1.5  (0.69) 1.7  (0.87) 1.7  (0.66) 2.5  (0.64) 1.3  (0.65)
Change from Baseline to 24 hours post-dose Number Analyzed 8 participants 1 participants 5 participants 4 participants 8 participants 9 participants 9 participants
0.0  (0.83) 0.0 [1]   (NA) 0.2  (1.09) -0.2  (1.03) 0.3  (0.69) -0.5  (0.91) 0.7  (1.53)
Change from Baseline to 48 hours post-dose Number Analyzed 6 participants 7 participants 4 participants 4 participants 1 participants 3 participants 3 participants
-0.5  (0.54) 0.1  (0.86) 0.2  (1.17) 0.1  (0.89) 0.4 [1]   (NA) -0.8  (0.5) -0.2  (1.95)
[1]
Cannot be calculated when n=1
15.Secondary Outcome
Title Change From Baseline in Abdominal Discomfort
Hide Description

Participants were asked to rate their abdominal discomfort for the past 24 hours using the following scale:

0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. Baseline was defined as the average abdominal discomfort score prior to receiving study drug (Day 1 to Day 15). Abdominal discomfort at 24 hours and 48 hours post-dose was calculated as the mean score from 0 to 24 and 0 to 48 hours post-dose respectively.

Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with available data at each time point.
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants
2.1  (0.63) 1.5  (0.98) 2.0  (0.75) 2.0  (0.74) 1.9  (0.81) 2.6  (0.77) 1.7  (0.77)
Change from Baseline to 24 hours post-dose Number Analyzed 8 participants 1 participants 5 participants 4 participants 8 participants 9 participants 9 participants
-0.2  (0.78) -0.8 [1]   (NA) -0.5  (0.80) -0.7  (1.30) 0.3  (0.60) -0.1  (0.96) 1.3  (0.90)
Change from Baseline to 48 hours post-dose Number Analyzed 6 participants 7 participants 4 participants 4 participants 1 participants 3 participants 3 participants
-0.4  (0.67) -0.3  (1.00) -0.2  (1.00) -0.4  (0.44) 1.1 [1]   (NA) -1.1  (1.07) -0.1  (1.59)
[1]
Cannot be calculated when n=1
16.Secondary Outcome
Title Change From Baseline in BM Consistency
Hide Description

Consistency of BMs was measured using the Bristol Stool Scale, as follows:

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.

Baseline was defined as the average consistency of BMs prior to receiving study drug (Day 1 to Day 15). BM consistency at 24 hours and 48 hours post-dose was calculated as the average scores from all bowel movements from 0 to 24 and 0 to 48 hours post-dose, respectively.

Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with available data at each time point.
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 18 participants 9 participants 9 participants 9 participants 9 participants 9 participants 9 participants
2.9  (1.24) 3.2  (1.13) 2.2  (1.12) 3.0  (1.71) 3.2  (1.33) 3.2  (2.06) 2.2  (0.81)
Change from Baseline to 24 hours post-dose Number Analyzed 8 participants 1 participants 5 participants 4 participants 8 participants 9 participants 9 participants
-1.4  (1.09) -3.0 [1]   (NA) -0.0  (0.24) -1.4  (1.56) 1.5  (1.44) 1.9  (3.27) 4.1  (1.07)
Change from Baseline to 48 hours post-dose Number Analyzed 6 participants 7 participants 4 participants 4 participants 1 participants 3 participants 3 participants
-1.0  (1.45) 0.2  (2.45) -0.3  (1.43) -1.0  (2.00) 0.6 [1]   (NA) 0.7  (3.66) 2.5  (1.88)
[1]
Cannot be calculated when n=1
17.Secondary Outcome
Title Change From Baseline in Number of False Start Bowel Movements Per Day
Hide Description

A false start was defined as any attempted, but unsuccessful bowel movement (no solid or liquid fecal material was excreted) based on the question “In the past 24 hours, how many times did you try to have a bowel movement but were unsuccessful?" Baseline was defined as the average number of false start BMs per day prior to receiving study drug (Day 1 to Day 15).

The number of false start BMs per day at 24 hours and 48 hours post-dose was calculated as is the average number of false start BMs per day from 0 to 24 and 0 to 48 hours post-dose, respectively.

Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: false start bowel movements / day
Baseline 0.56  (0.86) 0.67  (1.00) 0.67  (1.12) 0.22  (0.44) 0.56  (1.01) 0.00  (0.00) 0.33  (0.50)
Change from Baseline to 24 hours post-dose 0.28  (0.89) 0.44  (1.33) -0.11  (1.17) 0.00  (0.50) -0.11  (0.60) 2.56  (3.81) 0.78  (1.79)
Change from Baseline to 48 hours post-dose 0.25  (0.69) 0.28  (1.18) 0.22  (1.48) 0.00  (0.50) -0.06  (0.58) 1.61  (2.42) 0.44  (0.77)
18.Secondary Outcome
Title Change From Baseline in the Number of Bowel Movements With No Straining Per Day
Hide Description

Straining during BMs was graded using the following scale:

0 = Absent; 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Very Severe. A BM without straining was defined as a BM with a straining score = 0.

Baseline was defined as the average number of BMs without straining per day prior to receiving study drug (Day 1 to Day 15). The number of BMs without straining per day at 24 hours and 48 hours post-dose was calculated as the average number of BMs with no straining per day from 0 to 24 hours and 0 to 48 hours post-dose, respectively.

Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: bowel movements with no straining / day
Baseline 0.03  (0.07) 0.09  (0.11) 0.05  (0.09) 0.03  (0.07) 0.05  (0.07) 0.03  (0.05) 0.07  (0.11)
Change from Baseline to 24 hours post-dose -0.03  (0.07) -0.09  (0.11) 0.06  (0.36) -0.03  (0.07) 0.28  (0.71) 0.41  (0.74) 3.37  (2.16)
Change from Baseline to 48 hours post-dose -0.01  (0.14) -0.03  (0.13) 0.01  (0.21) -0.03  (0.07) 0.12  (0.36) 0.19  (0.38) 1.76  (1.02)
19.Secondary Outcome
Title Change From Baseline in Number of Rescue Medications Used Per Day
Hide Description Baseline was defined as the average number of rescue medications used per day prior to receiving study drug (Day 1 to Day 15). The number of rescue medications used per day at 24 hours and 48 hours post-dose was calculated as the average number of rescue medications used per day from 0 to 24 hours and 0 to 48 hours post-dose, respectively.
Time Frame Baseline, 24 hours post-dose and 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population; LOCF imputation was used
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: rescue medications / day
Baseline 0.31  (0.36) 0.18  (0.21) 0.36  (0.43) 0.53  (0.68) 0.52  (0.84) 0.28  (0.36) 0.20  (0.24)
Change from Baseline to 24 hours post-dose -0.04  (0.70) -0.18  (0.21) -0.36  (0.43) 0.02  (1.13) -0.52  (0.84) -0.28  (0.36) -0.20  (0.24)
Change from Baseline to 48 hours post-dose -0.04  (0.51) -0.01  (0.36) -0.25  (0.37) 0.08  (0.80) -0.52  (0.84) -0.23  (0.38) -0.20  (0.24)
20.Secondary Outcome
Title Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score > 8 at Any Time During the Study
Hide Description The COWS assessment consisted of 11 questions which rated the severity of opiate withdrawal symptoms, including resting pulse rate, gastrointestinal upset, sweating, restlessness, pupil size, tremor, anxiety or irritability, bone or joint aches, gooseflesh skin, yawning, and runny nose or tearing. Each symptom was rated on a scale from 0 (not present) to 4 or 5 (most severe). The total score was calculated by summing the 11 individual scores and ranged from 0 (no withdrawal symptoms) to 48 (worst symptoms).
Time Frame The COWS assessments were performed at Screening, on Day 14, Day 15 (pre-dose and 1, 2, 3, 4, 5, 6 and 8 hours post-dose, and at unscheduled times as signs or symptoms indicate), on Days 16 and 17, and on Day 24/End of Study.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 18.5)
0.0
(0.0 to 33.6)
0.0
(0.0 to 33.6)
0.0
(0.0 to 33.6)
0.0
(0.0 to 33.6)
11.1
(0.3 to 48.2)
66.7
(29.9 to 92.5)
21.Secondary Outcome
Title Percentage of Participants With Webster Opiate Withdrawal Scale (WOWS) Score > 8 at Any Time During the Study
Hide Description The Webster Opiate Withdrawal Scale (WOWS) assessment consisted of 7 questions which rate the severity of opiate withdrawal symptoms, including sweating, sleep, bone or joint aches, runny nose or tearing, gastrointestinal upset, anxiety or irritability and gooseflesh skin. Each symptom was rated on a scale from 0 (not present/no issues) to 4 or 5 (severe). The total score was calculated by summing the 7 individual scores and ranged from 0 (no withdrawal symptoms) to 29 (worst symptoms).
Time Frame The WOWS assessment was performed at Screening, Day 14, Day 15 at pre-dose , and 24 and 48 hours post-dose and at the Follow-up/End of Study visit (Day 24).
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Hide Analysis Population Description
Safety population
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions.
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 18 9 9 9 9 9 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 18.5)
0.0
(0.0 to 33.6)
0.0
(0.0 to 33.6)
0.0
(0.0 to 33.6)
11.1
(0.3 to 48.2)
0.0
(0.0 to 33.6)
0.0
(0.0 to 33.6)
22.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
Hide Description The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method.
Time Frame Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
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The pharmacokinetic (PK) analysis population included all randomized participants who received study drug and had at least one post-dose PK assessment completed.
Arm/Group Title Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 9 9 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Naldemedine
0.0837
(29.6%)
0.290
(28.9%)
1.00
(28.4%)
3.12
(30.2%)
9.68
(31.3%)
30.9
(44.2%)
Nor-S-297995
NA [1] 
(NA%)
NA [1] 
(NA%)
0.0713
(31.8%)
0.134
(27.6%)
0.526
(49.4%)
1.50
(53.3%)
[1]
Nor-S-297995 could not be quantified
23.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration of Naldemedine and Metabolite Nor-S-297995
Hide Description The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method.
Time Frame Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 9 9 9 9 9 9
Median (Full Range)
Unit of Measure: hours
Naldemedine
0.75
(0.5 to 3.0)
1.0
(0.5 to 4.0)
2.5
(0.5 to 5.0)
1.0
(0.72 to 3.0)
1.0
(0.75 to 2.0)
0.75
(0.50 to 1.0)
Nor-S-297995
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
5.0
(2.5 to 12)
4.1
(3.0 to 8.0)
8.0
(4.0 to 12)
5.0
(3.0 to 10)
[1]
Nor-S-297995 could not be quantified
24.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration of Naldemedine and Metabolite Nor-S-297995
Hide Description The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Area under the plasma concentration versus time curve from time zero to the last sampling time at which concentrations were at or above the limit of quantitation, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations (Linear Up/ Log Down).
Time Frame Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
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Hide Analysis Population Description
PK population
Arm/Group Title Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 9 9 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL)
Naldemedine
0.5863
(34.3%)
2.111
(31.4%)
11.71
(21.4%)
31.29
(30.5%)
93.60
(34.6%)
218.2
(37.6%)
Nor-S-297995
NA [1] 
(NA%)
NA [1] 
(NA%)
0.5856
(232.7%)
1.869
(68.3%)
14.97
(76.3%)
41.94
(63.3%)
[1]
Nor-S-297995 could not be quantified
25.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Naldemedine and Metabolite Nor-S-297995
Hide Description The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Area under the plasma concentration versus time curve from time zero to infinity, calculated using the formula: AUC0-inf = AUC0-t + Ct/λZ where Ct was the last measurable concentration and λZ was the apparent terminal elimination rate constant.
Time Frame Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 9 9 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Naldemedine
0.8023
(33.8%)
2.294
(30.2%)
12.04
(21.7%)
31.87
(29.9%)
94.53
(34.8%)
219.9
(37.8%)
Nor-S-297995
NA [1] 
(NA%)
NA [1] 
(NA%)
3.046
(63.0%)
4.515
(58.8%)
17.10
(73.4%)
44.91
(63.6%)
[1]
Nor-S-297995 could not be quantified
26.Secondary Outcome
Title Apparent Elimination Half-life of Naldemedine and Metabolite Nor-S-297995
Hide Description The plasma concentration of naldemedine and its metabolite Nor-S-297995 were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. The apparent elimination half-life was calculated using the formula t1/2,z = (ln2)/λZ
Time Frame Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description:
Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions.
Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions.
Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 1 mg naldemedine tablets administered on Day 15 under fasted conditions.
Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
Overall Number of Participants Analyzed 9 9 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Naldemedine
8.13
(58.3%)
7.46
(38.5%)
12.6
(35.6%)
12.2
(34.6%)
10.8
(20.9%)
11.6
(20.8%)
Nor-S-297995
NA [1] 
(NA%)
NA [1] 
(NA%)
24.6
(52.7%)
25.7
(61.8%)
16.0
(24.8%)
17.0
(18.1%)
[1]
Nor-S-297995 could not be quantified
Time Frame From first dose of study drug on Day 15 up to Day 24 (10 days).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Hide Arm/Group Description Participants received a single dose of matching placebo administered orally on Day 15 under fasted conditions. Participants received a single dose of 0.01 mg naldemedine oral solution administered on Day 15 under fasted conditions. Participants received a single dose of 0.03 mg naldemedine oral solution administered on Day 15 under fasted conditions. Participants received one 0.1 mg naldemedine tablet administered on Day 15 under fasted conditions. Participants received a single dose of 0.3 mg naldemedine tablets administered on Day 15 under fasted conditions. Participants received a single dose of 1mg naldemedine tablets administered on Day 15 under fasted conditions. Participants received a single dose of 3 mg naldemedine tablets administered on Day 15 under fasted conditions.
All-Cause Mortality
Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Pooled Placebo Naldemedine 0.01 mg Naldemedine 0.03 mg Naldemedine 0.1 mg Naldemedine 0.3 mg Naldemedine 1 mg Naldemedine 3 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/18 (50.00%)   6/9 (66.67%)   6/9 (66.67%)   5/9 (55.56%)   9/9 (100.00%)   9/9 (100.00%)   9/9 (100.00%) 
Ear and labyrinth disorders               
Tinnitus  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Eye disorders               
Lacrimation increased  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Gastrointestinal disorders               
Abdominal pain  1  3/18 (16.67%)  2/9 (22.22%)  1/9 (11.11%)  1/9 (11.11%)  6/9 (66.67%)  6/9 (66.67%)  9/9 (100.00%) 
Nausea  1  3/18 (16.67%)  4/9 (44.44%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  7/9 (77.78%)  6/9 (66.67%) 
Diarrhoea  1  1/18 (5.56%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  3/9 (33.33%)  8/9 (88.89%) 
Vomiting  1  1/18 (5.56%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  3/9 (33.33%)  6/9 (66.67%) 
Flatulence  1  2/18 (11.11%)  2/9 (22.22%)  0/9 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  1/9 (11.11%)  1/9 (11.11%) 
Abdominal pain upper  1  1/18 (5.56%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  1/9 (11.11%)  1/9 (11.11%) 
Abdominal discomfort  1  1/18 (5.56%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Abdominal distension  1  1/18 (5.56%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  1/9 (11.11%)  0/9 (0.00%) 
Dyspepsia  1  1/18 (5.56%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  1/9 (11.11%) 
Retching  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  0/9 (0.00%) 
Abdominal tenderness  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Eructation  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Tongue discolouration  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Proctalgia  1  0/18 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
General disorders               
Chills  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  2/9 (22.22%)  6/9 (66.67%) 
Oedema peripheral  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Drug withdrawal syndrome  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Fatigue  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Pyrexia  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Venipuncture site thrombosis  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Infusion site rash  1  0/18 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Infections and infestations               
Oral herpes  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Injury, poisoning and procedural complications               
Sunburn  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Investigations               
Oxygen saturation decreased  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  4/9 (44.44%) 
Cardiac murmur  1  2/18 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Blood glucose decreased  1  1/18 (5.56%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Blood prolactin increased  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Heart rate irregular  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Weight decreased  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Metabolism and nutrition disorders               
Dehydration  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Musculoskeletal chest pain  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Nervous system disorders               
Dizziness  1  1/18 (5.56%)  2/9 (22.22%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  3/9 (33.33%) 
Headache  1  0/18 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  3/9 (33.33%) 
Lethargy  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Hypoaesthesia  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Migraine  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Paraesthesia  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Somnolence  1  1/18 (5.56%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Renal and urinary disorders               
Dysuria  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders               
Dyspnoea  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Oropharyngeal pain  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Rhinorrhoea  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%) 
Wheezing  1  0/18 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%) 
Skin and subcutaneous tissue disorders               
Hyperhidrosis  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  1/9 (11.11%)  4/9 (44.44%)  6/9 (66.67%) 
Cold sweat  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Rash  1  0/18 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Vascular disorders               
Pallor  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  2/9 (22.22%) 
Flushing  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Hot flush  1  0/18 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%) 
Hypotension  1  0/18 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Results Point of Contact
Name/Title: Shionogi Clinical Trials Administrator
Organization: Shionogi Inc.
Phone: 800-849-9707
Responsible Party: Shionogi Inc. ( Shionogi )
ClinicalTrials.gov Identifier: NCT01122030     History of Changes
Other Study ID Numbers: 1007V9214
First Submitted: May 10, 2010
First Posted: May 12, 2010
Results First Submitted: April 19, 2017
Results First Posted: May 30, 2017
Last Update Posted: May 30, 2017