Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neoplasms; Constipation; Opioid-Related Disorders	Drug: Methylnaltrexone bromide	Phase 2

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 Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	12 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Supportive Care
Official Title:	Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients
Study Start Date :	October 2009
Actual Primary Completion Date :	December 2013
Actual Study Completion Date :	December 2013

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Drug: 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; Other Name: Relistor

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 4 hours after the dose of subcutaneous methylnaltrexone ]

Secondary Outcome Measures :

1. Laxation After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 24 and 48 hours after the dose of subcutaneous methylnaltrexone ]
2. Time to Laxation After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ]
3. 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 ]
4. 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 ]
5. Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ]
6. Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ]
7. Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

University of Vermont

Investigators

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

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mori M, Ji Y, Kumar S, Ashikaga T, Ades S. Phase II trial of subcutaneous methylnaltrexone in the treatment of severe opioid-induced constipation (OIC) in cancer patients: an exploratory study. Int J Clin Oncol. 2017 Apr;22(2):397-404. doi: 10.1007/s10147-016-1041-6. Epub 2016 Sep 15.

Responsible Party:	Steven Ades, Associate Professor, University of Vermont
ClinicalTrials.gov Identifier:	NCT01004393 History of Changes
Other Study ID Numbers:	VCC 0911; VCC 0911 ( Other Identifier: Vermont Cancer Center )
First Posted:	October 29, 2009
Results First Posted:	February 2, 2016
Last Update Posted:	February 2, 2016
Last Verified:	December 2015

Keywords provided by Steven Ades, University of Vermont:

Methylnaltrexone; Constipation; Narcotic Antagonists; Analgesics, Opioid; Neoplasms

Additional relevant MeSH terms:

Constipation; Opioid-Related Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Analgesics, Opioid; Bromides; Methylnaltrexone	Naltrexone; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anticonvulsants; Narcotic Antagonists