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Long Term Safety of Naldemedine

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01965652
First Posted: October 18, 2013
Last Update Posted: May 30, 2017
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.
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )
  Purpose
The purpose of this study is to evaluate the long-term safety of naldemedine for the treatment of constipation due to opioid therapy.

Condition Intervention Phase
Opioid-induced Constipation Drug: Naldemedine Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study to Evaluate the Long-term Safety of Naldemedine for the Treatment of Opioid-induced Constipation in Subjects With Non-malignant Chronic Pain Receiving Opioid Therapy

Resource links provided by NLM:


Further study details as provided by Shionogi Inc. ( Shionogi ):

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 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 Outcome Measures:
  • Change From Baseline in the Number of Bowel Movements Per Week [ Time Frame: 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).

  • Percentage of Participants Meeting Each Criterion of Laxative Use [ Time Frame: 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.


  • Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms [ Time Frame: 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.

  • Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score [ Time Frame: 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.


  • Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score [ Time Frame: 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.

  • Change From Baseline in the PAC-SYM Stool-symptoms Domain Score [ Time Frame: 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.


  • Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score [ Time Frame: 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.


  • Change From Baseline in the Physical Discomfort Domain of PAC-QOL [ Time Frame: 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.


  • Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL [ Time Frame: 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.


  • Change From Baseline in the Worries and Concerns Domain of PAC-QOL [ Time Frame: 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 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.


  • Change From Baseline in the Satisfaction Domain of PAC-QOL [ Time Frame: 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 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.


  • Participant Global Satisfaction [ Time Frame: Week 52 or early termination visit ]

    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


Enrollment: 1246
Actual Study Start Date: September 24, 2013
Study Completion Date: January 12, 2016
Primary Completion Date: January 12, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Naldemedine
Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.
Drug: Naldemedine
Naldemedine 0.2 mg tablet taken orally once a day
Other Names:
  • S-297995
  • Symproic®
Placebo Comparator: Placebo
Participants received matching placebo tablets orally once daily for 52 weeks.
Drug: Placebo
Placebo tablet taken orally once a day

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Subjects aged 18 to 80 years inclusive at the time of informed consent
  2. Subjects must have non-malignant chronic pain treated and must have opioid induced constipation (OIC)
  3. Subjects must be treated with a stable opioid regimen at a total daily dose on average of ≥ 30 mg equivalents of oral morphine sulfate
  4. Subjects may or may not be on a routine laxative regimen at the time of Screening

Exclusion Criteria

  1. Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
  2. Evidence of active medical diseases affecting bowel transit
  3. History of pelvic disorders that may be a cause of constipation
  4. Surgery (except for minor procedures) within 60 days of Screening
  5. History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation (e.g. mechanical GI obstruction)
  6. Subjects who have never taken laxatives for the treatment of OIC
  7. Current use of any prohibited medication including opioid antagonists, partial or mixed agonists/antagonists
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01965652


  Show 186 Study Locations
Sponsors and Collaborators
Shionogi
Investigators
Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi
  More Information

Responsible Party: 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: May 30, 2017
Last Verified: May 2016

Keywords provided by Shionogi Inc. ( Shionogi ):
Opioid Induced Constipation

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms