Trial · NCT01965652

Long Term Safety of Naldemedine

NCT01965652, Phase 3, Completed, Shionogi; results first posted 2017-05-30

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Long Term Safety of Naldemedine. Trials, record NCT01965652. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01965652

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Long Term Safety of Naldemedine
NCT number: NCT01965652
Status: Completed
Phases: Phase 3
Enrollment: 1,246 participants, actual
Lead sponsor: Shionogi
Conditions: Opioid-induced Constipation
Interventions: Naldemedine, Placebo
First posted: 2013-10-18
Last updated: 2018-04-18
Results first posted: 2017-05-30

Source ClinicalTrials.gov

Registered outcomes13

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Number of Participants With Adverse Events	From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).	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.
Secondary	Change From Baseline in the Number of Bowel Movements Per Week	Baseline and Weeks 12, 24, 36, and 52	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).
Secondary	Percentage of Participants Meeting Each Criterion of Laxative Use	From 28 days prior to screening until the end of the treatment period (total of 56 weeks)	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.
Secondary	Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms	Baseline and Weeks 2, 12, 24, 36, and 52	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.
Secondary	Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score	Baseline and Weeks 2, 12, 24, 36, and 52	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.
Secondary	Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score	Baseline and Weeks 2, 12, 24, 36, and 52	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.
Secondary	Change From Baseline in the PAC-SYM Stool-symptoms Domain Score	Baseline and Weeks 2, 12, 24, 36, and 52	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.
Secondary	Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score	Baseline and Weeks 2, 12, 24, 36, and 52	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.
Secondary	Change From Baseline in the Physical Discomfort Domain of PAC-QOL	Baseline and Weeks 2, 12, 24, 36, and 52	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.
Secondary	Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL	Baseline and Weeks 2, 12, 24, 36, and 52	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.

1 to 10 of 13Source ClinicalTrials.gov

See all 13 registered outcomes

Outcomes13

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Number of Participants With Adverse Events	From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).	Safety population	participants	NUMBER
SECONDARY	Change From Baseline in the Number of Bowel Movements Per Week	Baseline and Weeks 12, 24, 36, and 52	The intent-to-treat population includes all randomized participants. Five participants were excluded due to double enrollment at different sites.	bowel movements / week	LEAST_SQUARES_MEAN
SECONDARY	Percentage of Participants Meeting Each Criterion of Laxative Use	From 28 days prior to screening until the end of the treatment period (total of 56 weeks)	Intent-to-treat population	percentage of participants	NUMBER
SECONDARY	Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms	Baseline and Weeks 2, 12, 24, 36, and 52	The intent-to-treat population includes all randomized participants. Five participants were excluded due to double enrollment at different sites.	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score	Baseline and Weeks 2, 12, 24, 36, and 52	Intent-to-treat population	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score	Baseline and Weeks 2, 12, 24, 36, and 52	Intent-to-treat population	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the PAC-SYM Stool-symptoms Domain Score	Baseline and Weeks 2, 12, 24, 36, and 52	Intent-to-treat population	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score	Baseline and Weeks 2, 12, 24, 36, and 52	Intent-to-treat	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the Physical Discomfort Domain of PAC-QOL	Baseline and Weeks 2, 12, 24, 36, and 52	Intent-to-treat population	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL	Baseline and Weeks 2, 12, 24, 36, and 52	Intent-to-treat population	units on a scale	LEAST_SQUARES_MEAN

1 to 10 of 13Source ClinicalTrials.gov

See all 13 outcomes

Results by group136

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Units
Number of Participants With Adverse Events	Naldemedine	Adverse events	425	participants
Number of Participants With Adverse Events	Placebo	Adverse events	446	participants
Number of Participants With Adverse Events	Naldemedine	Adverse drug reactions	149	participants
Number of Participants With Adverse Events	Placebo	Adverse drug reactions	121	participants
Number of Participants With Adverse Events	Naldemedine	AEs leading to discontinuation of study drug	39	participants
Number of Participants With Adverse Events	Placebo	AEs leading to discontinuation of study drug	36	participants
Number of Participants With Adverse Events	Naldemedine	Serious adverse events	60	participants
Number of Participants With Adverse Events	Placebo	Serious adverse events	73	participants
Number of Participants With Adverse Events	Naldemedine	Serious adverse drug reactions	3	participants
Number of Participants With Adverse Events	Placebo	Serious adverse drug reactions	6	participants

1 to 10 of 136Source ClinicalTrials.gov

See all 136 results by group

Participant flow8

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Naldemedine	623
Overall Study	STARTED	Placebo	623
Overall Study	Received Treatment	Naldemedine	622
Overall Study	Received Treatment	Placebo	623
Overall Study	COMPLETED	Naldemedine	413
Overall Study	COMPLETED	Placebo	413
Overall Study	NOT COMPLETED	Naldemedine	210
Overall Study	NOT COMPLETED	Placebo	210

Source ClinicalTrials.gov

Adverse events268

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Upper Respiratory Tract Infection	Infections and infestations	Naldemedine	36	621
other	Upper Respiratory Tract Infection	Infections and infestations	Placebo	33	619
other	Urinary Tract Infection	Infections and infestations	Naldemedine	38	621
other	Urinary Tract Infection	Infections and infestations	Placebo	51	619
other	Headache	Nervous system disorders	Naldemedine	28	621
other	Headache	Nervous system disorders	Placebo	33	619
other	Abdominal Pain	Gastrointestinal disorders	Naldemedine	50	621
other	Abdominal Pain	Gastrointestinal disorders	Placebo	18	619
other	Diarrhoea	Gastrointestinal disorders	Naldemedine	68	621
other	Diarrhoea	Gastrointestinal disorders	Placebo	33	619

1 to 10 of 268Source ClinicalTrials.gov

See all 268 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Naldemedine
Total, all-cause mortality	Placebo
Total, other adverse events	Naldemedine	225	621
Total, other adverse events	Placebo	179	619
Total, serious adverse events	Naldemedine	60	621
Total, serious adverse events	Placebo	73	619

Source ClinicalTrials.gov

Papers3

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
32086791	DERIVED	PubMed
32280263	DERIVED	PubMed
34295186	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons1

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison
Naldemedine vs Placebo: serious adverse events

Source Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

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