Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

December 29, 2015 updated by: Steven Ades, University of Vermont

Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients

The purpose of this study is to evaluate the efficacy of methylnaltrexone in relieving opioid-induced constipation in cancer patients at various stages of disease.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Pain is one of the most common and important symptoms of cancer, often requiring opioid analgesics for control. However constipation is one of the most frequent and debilitating side effects of opioids, occurring in 40%-70% of patients being treated for chronic pain. Although laxatives are commonly used to manage opioid-induced constipation, these agents are not always effective or satisfactory. Methylnaltrexone bromide is a peripherally acting antagonist of the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is limited. This allows methylnaltrexone to function as a peripherally-acting antagonist in the gastrointestinal tract without impacting opioid-mediated analgesic effects in the central nervous system. The efficacy and safety of methylnaltrexone in treating opioid-induced constipation in patients with advanced disease receiving palliative care has been demonstrated. However the efficacy of this agent has not been evaluated in more active patients who are earlier in their disease course. The present study will evaluate the efficacy and safety of methylnaltrexone for the relief of severe opioid-induced constipation in this population and will attempt to identify factors predictive of methylnaltrexone response.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Vermont
      • Burlington, Vermont, United States, 05401
        • Fletcher Allen Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed neoplasm
  • 18 years of age or older
  • Have received opioids for analgesia for at least 2 weeks and been on a stable regimen of opioids and laxatives for 3 or more days before study entry
  • Fewer than three laxation during the preceding week and no laxation within 24 hours before study entry, or no laxation within 48 hours before study entry
  • Life expectancy of at least 6 months
  • World Health Organization Performance Status 0-3
  • Women of childbearing potential must have a negative pregnancy test
  • Breastfeeding should be discontinued prior to study entry
  • Ability to understand and the willingness to sign a written informed consent document.
  • Laboratory values within a week of study entry:

Absolute neutrophil count > 1,500/microliter Hemoglobin > 7 g/dL Platelet count > 100,000/microliter Calculated calcium < 10.5 mg/dL Calculated creatinine clearance > 30 mg.min Alanine aminotransferase < 3 x upper limit of normal (ULN) Aspartate aminotransferase < 3 x ULN Alkaline phosphatase < 2.5 x ULN Bilirubin < 1.5 x ULN

Exclusion Criteria:

  • Constipation not primarily caused by opioids, such as mechanical gastrointestinal obstruction or ongoing vinca alkaloid administration
  • Indwelling peritoneal catheter
  • Clinically active diverticular disease
  • Fecal impaction
  • Acute surgical abdomen
  • Fecal ostomy
  • Peritoneal carcinomatosis
  • Known hypersensitivity to methylnaltrexone, naltrexone, or naloxone
  • Administration of any investigational drug or experimental product within the previous 30 days
  • Initiation of a new bowel regimen or prokinetic agents within a week of study entry

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methylnaltrexone bromide
A single dose of methylnaltrexone will be administered subcutaneously to eligible subjects based on weight at the study entry. Since we will include subjects at all stages of cancer management, administering this study drug is considered experimental. We will use the dose approved by FDA, i.e., 0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for weight less than 38 kg or greater than 114 kg; 8 mg (0.4 mL) for weight 38 kg to less than 62 kg; and 12 mg (0.6 mL) for weight 62 kg to 114 kg.
Methylnaltrexone bromide, dosage based on weight (0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for weight less than 38 kg or greater than 114 kg; 8 mg (0.4 mL) for weight 38 kg to less than 62 kg; and 12 mg (0.6 mL) for weight 62 kg to 114 kg), single dose
Other Names:
  • Relistor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone
Time Frame: 4 hours after the dose of subcutaneous methylnaltrexone
4 hours after the dose of subcutaneous methylnaltrexone

Secondary Outcome Measures

Outcome Measure
Time Frame
Laxation After Administration of Subcutaneous Methylnaltrexone
Time Frame: 24 and 48 hours after the dose of subcutaneous methylnaltrexone
24 and 48 hours after the dose of subcutaneous methylnaltrexone
Time to Laxation After Administration of Subcutaneous Methylnaltrexone
Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone
48 hours after the dose of subcutaneous methylnaltrexone
Overall Pain Scores (0-10; 0=no Pain, 10=Worst Pain) After Administration of Subcutaneous Methylnaltrexone
Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone
48 hours after the dose of subcutaneous methylnaltrexone
Symptoms of Opioid Withdrawal (Modified Himmelsbach Withdrawal Scales (Ranging 7-28 in Total; 1=None - 4=Severe for 7 Items)) After Administration of Subcutaneous Methylnaltrexone
Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone
48 hours after the dose of subcutaneous methylnaltrexone
Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone
Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone
48 hours after the dose of subcutaneous methylnaltrexone
Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone
Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone
48 hours after the dose of subcutaneous methylnaltrexone
Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone
Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone
48 hours after the dose of subcutaneous methylnaltrexone

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Steven Ades, MD, Fletcher Allen Health Care / University of Vermont College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

October 28, 2009

First Submitted That Met QC Criteria

October 28, 2009

First Posted (Estimate)

October 29, 2009

Study Record Updates

Last Update Posted (Estimate)

February 2, 2016

Last Update Submitted That Met QC Criteria

December 29, 2015

Last Verified

December 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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