Study Evaluating Subcutaneous Methylnaltrexone For Treatment Of Opioid-Induced Constipation In Patients With Advanced Illness

• ClinicalTrials.gov Identifier: NCT00672477
• Recruitment Status: Completed
• First Posted: May 6, 2008
• Results First Posted: March 8, 2018
• Last Update Posted: March 8, 2018
• Sponsor: Bausch Health Americas, Inc.
• Collaborator: Progenics Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Bausch Health Americas, Inc.

Tracking Information

• First Submitted Date: May 2, 2008
• First Posted Date: May 6, 2008
• Results First Submitted Date: February 7, 2018
• Results First Posted Date: March 8, 2018
• Last Update Posted Date: March 8, 2018
• Study Start Date: June 2008
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2018)

The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses [ Time Frame: 7 days ]

This outcome measures the proportion of subjects who had a rescue-free laxation (ie, bowel movement) within 4 hours after at least 2 of the first 4 doses of study drug. A "rescue free" laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation.

• Original Primary Outcome Measures (submitted: May 5, 2008): The effect of the intervention will be measured by bowel movements. [ Time Frame: 14 days ]

Current Secondary Outcome Measures (submitted: February 7, 2018)

Time to First Rescue-free Laxation (Following the First Dose of Study Drug). [ Time Frame: 14 days ]

This outcome measures the time from first dose of study drug to the first rescue-free laxation (ie, bowel movement). A "rescue free" laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation.

• Original Secondary Outcome Measures (submitted: May 5, 2008): Bowel movements and health outcome measures [ Time Frame: 14 days ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Subcutaneous Methylnaltrexone For Treatment Of Opioid-Induced Constipation In Patients With Advanced Illness
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study Of A Fixed Dose Of Subcutaneous Methylnaltrexone In Adults With Advanced Illness And Opioid-Induced Constipation: Efficacy, Safety, And Additional Health Outcomes
• Brief Summary: This study will evaluate the safety and efficacy of methylnaltrexone administered as subcutaneous injections in subjects who have opioid-induced constipation and an advanced illness. The hypothesis is that methylnaltrexone will be safe and effective in relieving opioid-induced constipation in these subjects.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Opioid-Induced Constipation

Intervention

• Drug: Methylnaltrexone
  Other Names:

  • MOA-728
  • Relistor
• Drug: Placebo
  Other Name: Control

Study Arms

• Experimental: Methylnaltrexone
  Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses). Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; or 0.4 mL (8 mg) every other day if weight between 38 and <62 kg. Subjects with impaired kidney function received reduced doses according to instructions in the Relistor prescribing information.
  Intervention: Drug: Methylnaltrexone
• Placebo Comparator: Placebo
  Placebo subcutaneously every other day for 14 days (ie, 7 doses). Subjects received 0.6 mL every other day if weight ≥ 62kg; or 0.4 mL every other day if weight between 38 and < 62 kg. Subjects with impaired kidney function received reduced volumes of placebo solution to match the volumes used in the experimental group.
  Intervention: Drug: Placebo

Publications *

• Liao SS, Slatkin NE, Stambler N. The Influence of Age on Central Effects of Methylnaltrexone in Patients with Opioid-Induced Constipation. Drugs Aging. 2021 Jun;38(6):503-511. doi: 10.1007/s40266-021-00850-w. Epub 2021 Mar 31. Erratum In: Drugs Aging. 2021 Apr 23;:
• Janku F, Johnson LK, Karp DD, Atkins JT, Singleton PA, Moss J. Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer. Ann Oncol. 2016 Nov;27(11):2032-2038. doi: 10.1093/annonc/mdw317. Epub 2016 Aug 29. Erratum In: Ann Oncol. 2018 Apr 1;29(4):1076.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 7, 2018): 237
• Original Estimated Enrollment (submitted: May 5, 2008): 350
• Actual Study Completion Date: February 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Is an adult 18 years of age or older
• Has a diagnosis of advanced illness (ie, a terminal illness such as incurable cancer or other end-stage disease)
• Has a life expectancy of at least 1 month.
• Is receiving opioids on a regular schedule (not just as-needed or rescue doses) for the control of pain or discomfort for at least 2 weeks before the first dose of study drug.
• Has constipation that is caused by opioid medications.

Exclusion Criteria:

• Has a known or suspected allergy to methylnaltrexone or other similar compounds (e.g. naltrexone or naloxone).
• Has a known or suspected mechanical gastrointestinal obstruction.
• Has any potential nonopioid cause of bowel dysfunction that might be a major contributor to the constipation.
• Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study.
• Receiving opioid antagonist or partial antagonist products.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Brazil, Canada, France, Germany, Italy, Mexico, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Denmark, Finland, Netherlands, Norway, Portugal

Administrative Information

• NCT Number: NCT00672477
• Other Study ID Numbers: 3200K1-4000; B2541005
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bausch Health Americas, Inc.
• Original Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
• Current Study Sponsor: Bausch Health Americas, Inc.
• Original Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Progenics Pharmaceuticals, Inc.

Investigators

• Study Director: Enoch Bortey; Bausch Health Americas, Inc.

• PRS Account: Bausch Health Americas, Inc.
• Verification Date: February 2018