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Trial record 1 of 1 for:    NCT01965652
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Long Term Safety of Naldemedine

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ClinicalTrials.gov Identifier: NCT01965652
Recruitment Status : Completed
First Posted : October 18, 2013
Results First Posted : May 30, 2017
Last Update Posted : April 18, 2018
Sponsor:
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Opioid-induced Constipation
Interventions Drug: Naldemedine
Drug: Placebo
Enrollment 1246
Recruitment Details This study was conducted at 195 clinical sites in North America (Canada and the United States), Europe (Belgium, Denmark, Estonia, France, Germany, Hungary, Poland, Spain, Sweden, and the United Kingdom), and Africa/Asia Pacific (Australia and South Africa)
Pre-assignment Details

Participants were randomized in a 1:1 ratio to receive naldemedine or placebo for 52 weeks. Randomization was stratified based on documented opioid use (average total daily dose [TDD] during the 14-consecutive-day qualifying period) as follows:

  • 30 - 100 mg equivalents of oral morphine sulfate.
  • > 100 mg equivalents of oral morphine sulfate.
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks. Participants received placebo tablets orally once daily for 52 weeks.
Period Title: Overall Study
Started 623 [1] 623 [2]
Received Treatment 622 623
Completed 413 413
Not Completed 210 210
Reason Not Completed
Adverse Event             40             37
Withdrawal by Subject             62             69
Lost to Follow-up             53             40
Protocol Violation             34             38
Death             3             4
Other - Miscellaneous             18             21
Pregnancy             0             1
[1]
Includes two participants who each enrolled at two different sites
[2]
Includes three participants who each enrolled at two different sites
Arm/Group Title Naldemedine Placebo Total
Hide Arm/Group Description Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks. Participants received placebo tablets orally once daily for 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 621 619 1240
Hide Baseline Analysis Population Description
The safety population included all participants who received at least 1 dose of study drug. Five participants (2 in the naldemedine group and 3 in the placebo group) were excluded due to double enrollment at different sites. One participant in the placebo arm received naldemedine in error and is included in the naldemedine arm for safety analyses.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 621 participants 619 participants 1240 participants
53.4  (11.68) 52.7  (10.55) 53.0  (11.13)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 621 participants 619 participants 1240 participants
< 40 years 75 68 143
≥ 40 to < 65 years 445 475 920
≥ 65 years 101 76 177
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 621 participants 619 participants 1240 participants
Female
383
  61.7%
402
  64.9%
785
  63.3%
Male
238
  38.3%
217
  35.1%
455
  36.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 621 participants 619 participants 1240 participants
Hispanic or Latino
47
   7.6%
42
   6.8%
89
   7.2%
Not Hispanic or Latino
574
  92.4%
577
  93.2%
1151
  92.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 621 participants 619 participants 1240 participants
American Indian or Alaska Native 2 7 9
Asian 5 7 12
Black or African American 120 108 228
Native Hawaiian or Other Pacific Islander 2 1 3
White 492 496 988
Stratification by Opioid Dose   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 621 participants 619 participants 1240 participants
30-100 mg 396 392 788
> 100 mg 225 227 452
[1]
Measure Description: Dose of opioid was calculated using maintenance and breakthrough morphine equivalent dose. If any participants were treated with < 30 mg, the participants were counted in the ‘30-100’ group.
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description

A serious adverse event was defined as any adverse event (AE) that resulted in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life threatening, or require hospitalization were considered an SAE when, based upon appropriate medical judgment, they jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

Adverse drug reactions (ADRs) were defined as adverse events that were considered by the investigator to be definitely, probably, or possibly related to study drug. Serious ADRs were defined as serious AEs considered by the investigator to be definitely, probably, or possibly related to study drug.

Time Frame From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 619
Measure Type: Number
Unit of Measure: participants
Adverse events 425 446
Adverse drug reactions 149 121
AEs leading to discontinuation of study drug 39 36
Serious adverse events 60 73
Serious adverse drug reactions 3 6
SAEs leading to discontinuation of study drug 7 12
Deaths 1 3
2.Secondary Outcome
Title Change From Baseline in the Number of Bowel Movements Per Week
Hide Description Participants monitored their bowel movements and completed a daily bowel habits diary the week prior to study visits (i.e. during Weeks 11, 23, 35, and 51).
Time Frame Baseline and Weeks 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants. Five participants were excluded due to double enrollment at different sites.
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: bowel movements / week
Week 12 3.70  (0.163) 2.42  (0.162)
Week 24 3.77  (0.172) 2.77  (0.172)
Week 36 3.88  (0.180) 2.88  (0.177)
Week 52 3.92  (0.184) 2.92  (0.187)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The significance level was set at 0.05 (2-sided). The analysis of efficacy endpoints was not adjusted for multiplicity; hence, the p-values are purely nominal. A mixed-effects model repeated measures (MMRM) method was used for the comparisons.
Method Mixed-effects model repeated measures
Comments The MMRM method included the opioid dose strata as a covariate and treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.83 to 1.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.226
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The MMRM method included the opioid dose strata as a covariate and treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.53 to 1.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.240
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The MMRM method included the opioid dose strata as a covariate and treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.52 to 1.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.249
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The MMRM method included the opioid dose strata as a covariate and treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.49 to 1.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.259
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Meeting Each Criterion of Laxative Use
Hide Description

Participants who were taking stable routine/regular laxatives at Screening were to continue taking the same regimen throughout the study.

The percentage of participants meeting each of the criteria below are reported:

1. Participants not on stable laxatives, defined as participants who did not use laxatives from 28 days prior to the Screening Period to the final dose of study drug or who received only rescue laxative. Rescue is defined as any laxative taken for the first time during the Treatment Period.

1a. Out of participants who were not on stable laxatives, participants who received rescue laxatives.

2. Participants on stable laxatives, defined as participants who may have had at least one/any stable laxative use reported from 28 days prior to Screening Period to the final dose of study drug.

2a. Out of participants who were on stable laxatives, participants who received rescue laxatives.

3. Participants who did not meet criteria 1 or 2.

Time Frame From 28 days prior to screening until the end of the treatment period (total of 56 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Measure Type: Number
Unit of Measure: percentage of participants
1. Participants not on stable laxatives Number Analyzed 621 participants 620 participants
30.0 29.5
1a. Who received rescue laxative Number Analyzed 186 participants 183 participants
7.0 13.1
2. Participants on stable laxatives Number Analyzed 621 participants 620 participants
50.2 54.0
2a. Who received rescue laxative Number Analyzed 312 participants 335 participants
8.0 14.0
3. Other participants Number Analyzed 621 participants 620 participants
19.8 16.5
4.Secondary Outcome
Title Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms
Hide Description The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The overall score was calculated as the mean of all 12 items and ranges from 0 (best) to 4 (worst). A negative change from baseline value indicates improvement.
Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants. Five participants were excluded due to double enrollment at different sites.
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.15  (0.036) -0.81  (0.036)
Week 12 -1.11  (0.039) -0.86  (0.039)
Week 24 -1.16  (0.039) -0.87  (0.039)
Week 36 -1.21  (0.040) -0.85  (0.040)
Week 52 -1.22  (0.041) -0.98  (0.042)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.44 to -0.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.050
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.36 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.055
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.40 to -0.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.056
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.47 to -0.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.057
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.35 to -0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.059
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score
Hide Description

The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The abdominal-symptom domain score was calculated as the mean of the following 4 items: abdominal discomfort, abdominal pain, abdominal bloating and stomach cramps.

A negative change from baseline value indicates improvement in symptoms.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -0.99  (0.038) -0.79  (0.038)
Week 12 -0.93  (0.042) -0.78  (0.043)
Week 24 -0.99  (0.043) -0.81  (0.043)
Week 36 -1.06  (0.043) -0.78  (0.043)
Week 52 -1.07  (0.045) -0.94  (0.045)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.31 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.054
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0173
Comments [Not Specified]
Method Mixed-effects model repeated meaures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.26 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.060
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.30 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.061
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.40 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.061
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0336
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.26 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.064
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score
Hide Description The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The abdominal-symptom domain score was calculated as the mean of the following 3 items: painful bowel movements, rectal burning during or after a bowel movement, and rectal bleeding or tearing during or after a bowel movement. A negative change from baseline value indicates improvement in symptoms.
Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.00  (0.040) -0.75  (0.040)
Week 12 -0.97  (0.044) -0.81  (0.045)
Week 24 -1.02  (0.046) -0.79  (0.046)
Week 36 -1.02  (0.045) -0.76  (0.045)
Week 52 -1.03  (0.046) -0.87  (0.047)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.37 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.057
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0114
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.28 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.063
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.36 to -0.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.065
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.38 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.064
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0119
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.29 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.066
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the PAC-SYM Stool-symptoms Domain Score
Hide Description

The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) asked participants to rate the severity of 12 constipation symptoms in the last 2 weeks on a scale from 0 (absent) to 4 (very severe). The stool-symptom domain score was calculated as the mean of the following 5 items: incomplete bowel movements, bowel movements that were too hard, bowel movements that were too small, straining or squeezing to try to pass bowel movements, and false-alarm bowel movements.

A negative change from baseline value indicates improvement in symptoms.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.37  (0.045) -0.86  (0.045)
Week 12 -1.34  (0.046) -0.96  (0.047)
Week 24 -1.37  (0.048) -0.97  (0.048)
Week 36 -1.44  (0.050) -0.96  (0.050)
Week 52 -1.45  (0.051) -1.08  (0.051)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.64 to -0.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.063
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.51 to -0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.066
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.54 to -0.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.067
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.62 to -0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.071
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.52 to -0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.072
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score
Hide Description

The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants’ daily life during the past 2 weeks.

Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The overall score was calculated as the mean of all 28 item scores. A negative change from baseline value indicates improvement.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.14  (0.033) -0.75  (0.033)
Week 12 -1.19  (0.036) -0.83  (0.037)
Week 24 -1.19  (0.038) -0.86  (0.038)
Week 36 -1.22  (0.039) -0.82  (0.039)
Week 52 -1.24  (0.039) -0.94  (0.040)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.49 to -0.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.047
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.46 to -0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.051
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.43 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.054
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.50 to -0.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.055
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.42 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.056
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in the Physical Discomfort Domain of PAC-QOL
Hide Description

The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants’ daily life during the past 2 weeks.

Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The physical discomfort domain consists of 4 questions related to bloating, feeling heavy, how much of the time participants felt any physical discomfort and how much time they felt the need to open their bowel but were not able to. The physical discomfort score was calculated as the mean of the 4 individual scores. A negative change from baseline value indicates improvement.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.33  (0.040) -0.94  (0.040)
Week 12 -1.27  (0.044) -0.95  (0.045)
Week 24 -1.26  (0.046) -0.98  (0.046)
Week 36 -1.28  (0.048) -0.94  (0.048)
Week 52 -1.38  (0.047) -1.09  (0.047)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.50 to -0.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.056
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Anaysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.44 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.063
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.40 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.065
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.48 to -0.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.068
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.41 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.067
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL
Hide Description

The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants’ daily life during the past 2 weeks.

Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The psychosocial discomfort domain consists of 8 questions related to participants’ embarrassment regarding their constipation and effects of constipation on eating habits and appetite.

The psychosocial discomfort score was calculated as the mean of the 8 individual scores. A negative change from baseline value indicates improvement.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -0.92  (0.036) -0.69  (0.036)
Week 12 -0.96  (0.039) -0.72  (0.039)
Week 24 -0.97  (0.040) -0.72  (0.040)
Week 36 -0.99  (0.042) -0.68  (0.042)
Week 52 -1.00  (0.043) -0.80  (0.043)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.34 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.051
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.35 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.055
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.36 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.057
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.43 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.059
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.33 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.061
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in the Worries and Concerns Domain of PAC-QOL
Hide Description

The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants’ daily life during the past 2 weeks.

Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The worries and concerns domain consists of 11 questions related to participants’ feelings and concerns about their constipation. The worries and concerns domain score was calculated as the mean of the 11 individual scores. A negative change from baseline value indicates improvement.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.14  (0.038) -0.74  (0.038)
Week 12 -1.21  (0.042) -0.85  (0.042)
Week 24 -1.19  (0.043) -0.87  (0.043)
Week 36 -1.23  (0.044) -0.81  (0.044)
Week 52 -1.24  (0.045) -0.92  (0.045)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.50 to -0.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.054
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.48 to -0.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.060
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.45 to -0.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.061
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.54 to -0.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.062
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.44 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.064
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in the Satisfaction Domain of PAC-QOL
Hide Description

The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) consists of 28 questions designed to measure the impact constipation has had on participants’ daily life during the past 2 weeks.

Each question was evaluated by the participant on a five-point scale ranging from 0 (not at all or none of the time) to 4 (extremely or all of the time), where higher scores represent poorer quality of life. The satisfaction domain consists of 5 questions related to participants’ feelings of satisfaction with their bowel function. The satisfaction domain score was calculated as the mean of the 5 individual scores. A negative change from baseline value indicates improvement.

Time Frame Baseline and Weeks 2, 12, 24, 36, and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 2 -1.37  (0.050) -0.70  (0.050)
Week 12 -1.45  (0.053) -0.87  (0.053)
Week 24 -1.50  (0.054) -0.99  (0.054)
Week 36 -1.53  (0.056) -1.00  (0.056)
Week 52 -1.54  (0.059) -1.07  (0.059)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 2 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.67
Confidence Interval (2-Sided) 95%
-0.81 to -0.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.070
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 12 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.73 to -0.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.075
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 24 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.66 to -0.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.077
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 36 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.69 to -0.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.080
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
Comments Week 52 Analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model repeated measures
Comments The mixed-effects model repeated measures (MMRM) method included treatment group, time, and time-by-treatment group interaction as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.64 to -0.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.083
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Participant Global Satisfaction
Hide Description

Participants were asked to rate their degree of satisfaction of constipation and abdominal symptoms from the start of study drug dosing to Week 52 (or early termination).

Satisfaction was rated based on the following seven grades:

  • Grade 1 = markedly worsened
  • Grade 2 = moderately worsened
  • Grade 3 = slightly worsened
  • Grade 4 = unchanged
  • Grade 5 = slightly improved
  • Grade 6 = moderately improved
  • Grade 7 = markedly improved
Time Frame Week 52 or early termination visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description:
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Participants received placebo tablets orally once daily for 52 weeks.
Overall Number of Participants Analyzed 621 620
Measure Type: Number
Unit of Measure: percentage of participants
Markedly worsened 2.4 2.0
Moderately worsened 0.6 2.8
Slightly worsened 1.0 2.2
Unchanged 14.9 33.5
Slightly improved 20.1 23.0
Moderately improved 26.0 17.7
Markedly improved 35.0 18.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Naldemedine, Placebo
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 Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).
Adverse Event Reporting Description The safety population included all participants who were randomized and received at least 1 dose of study drug and were analyzed by the treatment actually received. Five participants (2 in the naldemedine group and 3 in the placebo group) were excluded due to double enrollment at different sites. One participant in the placebo arm received naldemedine in error and is included in the naldemedine arm for safety analyses.
 
Arm/Group Title Naldemedine Placebo
Hide Arm/Group Description Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks. Participants received placebo tablets orally once daily for 52 weeks.
All-Cause Mortality
Naldemedine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Naldemedine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   60/621 (9.66%)   73/619 (11.79%) 
Cardiac disorders     
Acute Myocardial Infarction  1  2/621 (0.32%)  1/619 (0.16%) 
Angina Pectoris  1  0/621 (0.00%)  1/619 (0.16%) 
Angina Unstable  1  0/621 (0.00%)  2/619 (0.32%) 
Atrioventricular Block First Degree  1  0/621 (0.00%)  1/619 (0.16%) 
Cardiac Arrest  1  0/621 (0.00%)  1/619 (0.16%) 
Cardiac Failure Congestive  1  1/621 (0.16%)  2/619 (0.32%) 
Mitral Valve Incompetence  1  0/621 (0.00%)  1/619 (0.16%) 
Myocardial Infarction  1  1/621 (0.16%)  0/619 (0.00%) 
Sinus Tachycardia  1  1/621 (0.16%)  0/619 (0.00%) 
Congenital, familial and genetic disorders     
Sickle Cell Anaemia with Crisis  1  1/621 (0.16%)  0/619 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain  1  2/621 (0.32%)  1/619 (0.16%) 
Abdominal Pain Lower  1  0/621 (0.00%)  1/619 (0.16%) 
Colitis  1  0/621 (0.00%)  1/619 (0.16%) 
Constipation  1  1/621 (0.16%)  0/619 (0.00%) 
Flatulence  1  0/621 (0.00%)  1/619 (0.16%) 
Gastric Varices  1  0/621 (0.00%)  1/619 (0.16%) 
Gastric Volvulus  1  1/621 (0.16%)  0/619 (0.00%) 
Gastritis  1  0/621 (0.00%)  1/619 (0.16%) 
Gastrooesophageal Reflux Disease  1  0/621 (0.00%)  1/619 (0.16%) 
Impaired Gastric Emptying  1  0/621 (0.00%)  1/619 (0.16%) 
Small Intestinal Obstruction  1  0/621 (0.00%)  1/619 (0.16%) 
Vomiting  1  1/621 (0.16%)  1/619 (0.16%) 
General disorders     
Device Dislocation  1  1/621 (0.16%)  0/619 (0.00%) 
Non-Cardiac Chest Pain  1  1/621 (0.16%)  3/619 (0.48%) 
Surgical Failure  1  0/621 (0.00%)  1/619 (0.16%) 
Hepatobiliary disorders     
Bile Duct Stone  1  1/621 (0.16%)  0/619 (0.00%) 
Cholecystitis  1  0/621 (0.00%)  1/619 (0.16%) 
Cholelithiasis  1  1/621 (0.16%)  0/619 (0.00%) 
Hepatitis  1  1/621 (0.16%)  0/619 (0.00%) 
Infections and infestations     
Appendicitis  1  1/621 (0.16%)  0/619 (0.00%) 
Arthritis Bacterial  1  1/621 (0.16%)  0/619 (0.00%) 
Bronchitis  1  1/621 (0.16%)  0/619 (0.00%) 
Cellulitis  1  2/621 (0.32%)  2/619 (0.32%) 
Cellulitis Orbital  1  0/621 (0.00%)  1/619 (0.16%) 
Incision Site Infection  1  0/621 (0.00%)  1/619 (0.16%) 
Infected Skin Ulcer  1  0/621 (0.00%)  1/619 (0.16%) 
Lobar Pneumonia  1  1/621 (0.16%)  1/619 (0.16%) 
Localised Infection  1  0/621 (0.00%)  1/619 (0.16%) 
Necrotising Fasciitis  1  0/621 (0.00%)  1/619 (0.16%) 
Otitis Media  1  1/621 (0.16%)  0/619 (0.00%) 
Parotitis  1  1/621 (0.16%)  0/619 (0.00%) 
Pneumonia  1  7/621 (1.13%)  4/619 (0.65%) 
Pneumonia Bacterial  1  0/621 (0.00%)  1/619 (0.16%) 
Post Procedural Infection  1  0/621 (0.00%)  1/619 (0.16%) 
Sepsis  1  1/621 (0.16%)  2/619 (0.32%) 
Subcutaneous Abscess  1  1/621 (0.16%)  0/619 (0.00%) 
Tooth Abscess  1  0/621 (0.00%)  1/619 (0.16%) 
Tooth Infection  1  0/621 (0.00%)  1/619 (0.16%) 
Urinary Tract Infection Pseudomonal  1  0/621 (0.00%)  1/619 (0.16%) 
Urosepsis  1  0/621 (0.00%)  1/619 (0.16%) 
Viral Infection  1  0/621 (0.00%)  1/619 (0.16%) 
Injury, poisoning and procedural complications     
Accidental Overdose  1  1/621 (0.16%)  1/619 (0.16%) 
Lower Limb Fracture  1  1/621 (0.16%)  0/619 (0.00%) 
Overdose  1  2/621 (0.32%)  0/619 (0.00%) 
Patella Fracture  1  0/621 (0.00%)  1/619 (0.16%) 
Peripheral Artery Restenosis  1  0/621 (0.00%)  1/619 (0.16%) 
Post-Traumatic Neck Syndrome  1  0/621 (0.00%)  1/619 (0.16%) 
Postoperative Respiratory Failure  1  1/621 (0.16%)  0/619 (0.00%) 
Road Traffic Accident  1  0/621 (0.00%)  1/619 (0.16%) 
Traumatic Haematoma  1  0/621 (0.00%)  1/619 (0.16%) 
Wrist Fracture  1  0/621 (0.00%)  1/619 (0.16%) 
Investigations     
Blood Potassium Increased  1  1/621 (0.16%)  0/619 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/621 (0.00%)  1/619 (0.16%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/621 (0.16%)  0/619 (0.00%) 
Arthritis  1  0/621 (0.00%)  1/619 (0.16%) 
Back Pain  1  2/621 (0.32%)  5/619 (0.81%) 
Groin Pain  1  0/621 (0.00%)  1/619 (0.16%) 
Intervertebral Disc Degeneration  1  0/621 (0.00%)  2/619 (0.32%) 
Lumbar Spinal Stenosis  1  2/621 (0.32%)  0/619 (0.00%) 
Muscle Spasms  1  1/621 (0.16%)  0/619 (0.00%) 
Musculoskeletal Chest Pain  1  1/621 (0.16%)  1/619 (0.16%) 
Myalgia  1  1/621 (0.16%)  0/619 (0.00%) 
Neck Pain  1  2/621 (0.32%)  0/619 (0.00%) 
Osteoarthritis  1  5/621 (0.81%)  3/619 (0.48%) 
Rhabdomyolysis  1  0/621 (0.00%)  1/619 (0.16%) 
Spinal Column Stenosis  1  1/621 (0.16%)  0/619 (0.00%) 
Spinal Osteoarthritis  1  1/621 (0.16%)  1/619 (0.16%) 
Spondylolisthesis  1  1/621 (0.16%)  1/619 (0.16%) 
Tenosynovitis  1  1/621 (0.16%)  0/619 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma  1  1/621 (0.16%)  0/619 (0.00%) 
Adenocarcinoma of Colon  1  1/621 (0.16%)  0/619 (0.00%) 
Bladder Transitional Cell Carcinoma  1  0/621 (0.00%)  1/619 (0.16%) 
Breast Cancer  1  1/621 (0.16%)  0/619 (0.00%) 
Lung Adenocarcinoma  1  0/621 (0.00%)  1/619 (0.16%) 
Small Cell Lung Cancer  1  0/621 (0.00%)  1/619 (0.16%) 
Squamous Cell Carcinoma of Lung  1  1/621 (0.16%)  0/619 (0.00%) 
Nervous system disorders     
Carotid Artery Stenosis  1  1/621 (0.16%)  0/619 (0.00%) 
Carpal Tunnel Syndrome  1  0/621 (0.00%)  1/619 (0.16%) 
Cerebrovascular Accident  1  1/621 (0.16%)  1/619 (0.16%) 
Cervicobrachial Syndrome  1  1/621 (0.16%)  0/619 (0.00%) 
Headache  1  1/621 (0.16%)  0/619 (0.00%) 
Loss of Consciousness  1  1/621 (0.16%)  0/619 (0.00%) 
Metabolic Encephalopathy  1  0/621 (0.00%)  1/619 (0.16%) 
Spinal Claudication  1  0/621 (0.00%)  1/619 (0.16%) 
Toxic Encephalopathy  1  2/621 (0.32%)  0/619 (0.00%) 
Transient Ischaemic Attack  1  0/621 (0.00%)  1/619 (0.16%) 
Psychiatric disorders     
Acute Psychosis  1  0/621 (0.00%)  1/619 (0.16%) 
Confusional State  1  1/621 (0.16%)  0/619 (0.00%) 
Depression  1  0/621 (0.00%)  1/619 (0.16%) 
Mental Status Changes  1  0/621 (0.00%)  1/619 (0.16%) 
Panic Attack  1  1/621 (0.16%)  0/619 (0.00%) 
Psychotic Disorder  1  1/621 (0.16%)  1/619 (0.16%) 
Stress  1  1/621 (0.16%)  0/619 (0.00%) 
Suicidal Ideation  1  0/621 (0.00%)  1/619 (0.16%) 
Renal and urinary disorders     
Bladder Prolapse  1  0/621 (0.00%)  1/619 (0.16%) 
Nephrolithiasis  1  0/621 (0.00%)  1/619 (0.16%) 
Renal Failure  1  0/621 (0.00%)  1/619 (0.16%) 
Renal Failure Acute  1  0/621 (0.00%)  1/619 (0.16%) 
Urinary Retention  1  0/621 (0.00%)  1/619 (0.16%) 
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure  1  0/621 (0.00%)  1/619 (0.16%) 
Asthma  1  1/621 (0.16%)  1/619 (0.16%) 
Bronchitis Chronic  1  0/621 (0.00%)  1/619 (0.16%) 
Chronic Obstructive Pulmonary Disease  1  2/621 (0.32%)  3/619 (0.48%) 
Dyspnoea  1  1/621 (0.16%)  0/619 (0.00%) 
Pleurisy  1  0/621 (0.00%)  1/619 (0.16%) 
Pneumothorax  1  1/621 (0.16%)  0/619 (0.00%) 
Pulmonary Embolism  1  2/621 (0.32%)  0/619 (0.00%) 
Respiratory Failure  1  0/621 (0.00%)  1/619 (0.16%) 
Sinus Polyp  1  0/621 (0.00%)  1/619 (0.16%) 
Skin and subcutaneous tissue disorders     
Skin Necrosis  1  1/621 (0.16%)  0/619 (0.00%) 
Vascular disorders     
Arteriosclerosis  1  0/621 (0.00%)  1/619 (0.16%) 
Deep Vein Thrombosis  1  1/621 (0.16%)  1/619 (0.16%) 
Femoral Artery Occlusion  1  1/621 (0.16%)  0/619 (0.00%) 
Orthostatic Hypotension  1  1/621 (0.16%)  0/619 (0.00%) 
Peripheral Arterial Occlusive Disease  1  1/621 (0.16%)  0/619 (0.00%) 
Peripheral Vascular Disorder  1  1/621 (0.16%)  0/619 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Naldemedine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   225/621 (36.23%)   179/619 (28.92%) 
Gastrointestinal disorders     
Abdominal Pain  1  50/621 (8.05%)  18/619 (2.91%) 
Diarrhoea  1  68/621 (10.95%)  33/619 (5.33%) 
Nausea  1  49/621 (7.89%)  35/619 (5.65%) 
Vomiting  1  36/621 (5.80%)  18/619 (2.91%) 
Infections and infestations     
Upper Respiratory Tract Infection  1  36/621 (5.80%)  33/619 (5.33%) 
Urinary Tract Infection  1  38/621 (6.12%)  51/619 (8.24%) 
Musculoskeletal and connective tissue disorders     
Back Pain  1  34/621 (5.48%)  27/619 (4.36%) 
Nervous system disorders     
Headache  1  28/621 (4.51%)  33/619 (5.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
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 ext 1454
Responsible Party: Shionogi Inc. ( Shionogi )
ClinicalTrials.gov Identifier: NCT01965652     History of Changes
Other Study ID Numbers: 1326V9235
First Submitted: October 15, 2013
First Posted: October 18, 2013
Results First Submitted: April 19, 2017
Results First Posted: May 30, 2017
Last Update Posted: April 18, 2018