Symptoms and General Pathology

All Conditions

Substance Related Disorders

Behaviors and Mental Disorders

Constipation

Opioid-Related Disorders

Opioid-Induced Constipation

Signs and Symptoms, Digestive

Narcotic-Related Disorders

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Analgesics

All Drugs and Chemicals

Anticonvulsants

Central Nervous System Depressants

Narcotic Antagonists

Bromides

Analgesics, Opioid

Methylnaltrexone

Narcotics

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

Methylnaltrexone bromide

Steven Ades, MD

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.

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.

Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

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

University of Vermont

Associate Professor

Methylnaltrexone bromide: 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

Age, Continuous

Sex: Female, Male

Masanori Mori, MD

Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone

Rescue-free Laxation within 24 hours (n=12)

Laxation within 48 hours (n=12)

Laxation After Administration of Subcutaneous Methylnaltrexone

Mean time to rescue-free laxation ≤4 hours (n=11)

Mean time to rescue-free laxation ≤24 hours (n=11)

Mean time to laxation ≤48 hours (n=11)

Time to Laxation After Administration of Subcutaneous Methylnaltrexone

Average pain (0-4 hours) (n=12)

Average pain (4-24 hours) (n=12)

Average pain (24-48 hours) (n=12)

Overall Pain Scores (0-10; 0=no Pain, 10=Worst Pain) After Administration of Subcutaneous Methylnaltrexone

0-4 hours (n=12)

4-24 hours (n=12)

24-48 hours (n=11)

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

Frequency of ≥ 1 laxation (0-4 hours) (n=12)

Frequency of ≥ 1 laxation (4-24 hours) (n=12)

Frequency of ≥ 1 laxation (24-48 hours) (n=11)

Consistency (slight-very hard) (0-4 hours) (n=12)

Consistency (slight-very hard) (4-24 hours) (n=12)

Consistency (slight-very hard)(24-48 hours) (n=11)

Difficulty (severe-very severe) (0-4 hours) (n=12)

Difficulty (severe-very severe)(4-24 hours) (n=12)

Difficulty (severe-very severe)(24-48hours) (n=11)

Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone

Severity (severe-very severe) (0-4 hours) (n=12)

Severity (severe-very severe) (4-24 hours) (n=12)

Severity (severe-very severe) (24-48 hours) (n=11)

Distress (severe-very severe) (0-4 hours) (n=12)

Distress (severe-very severe) (4-24 hours) (n=12)

Distress (severe-very severe) (24-48 hours) (n=11)

Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone

Satisfied-very satisfied (0-4 hours) (n=12)

Satisfied-very satisfied (4-24 hours) (n=12)

Satisfied-very satisfied (24-48 hours) (n=11)

Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone

Overall Study

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Participants will receive methylnaltrexone bromide (MNTX) 450 mg (3 tablets of 150 mg each) QD orally. If the initial interim analysis suggests a lack of efficacy, subsequent participants will receive 450 mg MNTX twice daily (BID) or three times daily (TID). Treatment will continue until participant's death or early withdrawal from study or study completion at Day 168.

Participants will receive placebo matching to MNTX until participant's death or early withdrawal from study or study completion at Day 168.

Methylnaltrexone bromide will be administered per dose and schedule specified in the respective arm.

Placebo matching to methylnaltrexone bromide will be administered as mentioned in the respective arm.

Placebo

John Lahey

This is an adaptive design study. During the first phase of the study, participants will be randomized in 2:1 ratio to receive either MNTX 450 milligrams (mg) once daily (QD) or placebo. An interim analysis will be performed for futility and at that point a higher dosage regimen may be utilized for the active treatment group if the futility criteria are met. For the second stage of the study, interim analyses will be conducted for futility and sample size reassessment.

A Study of Methylnaltrexone Bromide (MNTX) in Participants With Advanced Pancreatic Cancer

A Phase II/III Adaptive Study to Evaluate the Safety and Efficacy of Oral Methylnaltrexone Bromide Tablets in Subjects With Advanced Pancreatic Cancer

Bausch Health Americas, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Methylnaltrexone for Opioid-induced Constipation in Cancer Patients	NCT01004393	Neoplasms Constipation Opioid-Related ...	Methylnaltrexon...	18 Years -	University of Vermont
A Study of Methylnaltrexone Bromide (MNTX) in Participants With Advanced Pancreatic Cancer	NCT04083651	Pancreatic Canc...	Methylnaltrexon... Placebo	18 Years -	Bausch Health Americas, Inc.
A Study of Methylnaltrexone Bromide (MNTX) in Participants With Advanced Pancreatic Cancer	NCT04083651	Pancreatic Canc...	Methylnaltrexon... Placebo	18 Years -	Bausch Health Americas, Inc.
Methylnaltrexone for Opioid-induced Constipation in Cancer Patients	NCT01004393	Neoplasms Constipation Opioid-Related ...	Methylnaltrexon...	18 Years -	University of Vermont

Spots Global Cancer Trial Database for methylnaltrexone bromide