- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01004393
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
Conditions
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
-
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Vermont
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Burlington, Vermont, United States, 05401
- Fletcher Allen Health Care
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-
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:
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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
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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.
Sponsor
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
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Signs and Symptoms, Digestive
- Narcotic-Related Disorders
- Constipation
- Opioid-Related Disorders
- Opioid-Induced Constipation
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Sensory System Agents
- Narcotic Antagonists
- Anticonvulsants
- Bromides
- Methylnaltrexone
Other Study ID Numbers
- VCC 0911 (Other Identifier: Vermont Cancer Center)
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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