Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Steven Ades, University of Vermont
ClinicalTrials.gov Identifier:
NCT01004393
First received: October 28, 2009
Last updated: December 29, 2015
Last verified: December 2015
  Purpose
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 Intervention Phase
Neoplasms
Constipation
Opioid-Related Disorders
Drug: Methylnaltrexone bromide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 4 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Laxation After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 24 and 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]
  • Time to Laxation After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]
  • Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: Yes ]
  • Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: October 2009
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004393

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

Responsible Party: Steven Ades, Associate Professor, University of Vermont
ClinicalTrials.gov Identifier: NCT01004393     History of Changes
Other Study ID Numbers: VCC 0911  VCC 0911 
Study First Received: October 28, 2009
Results First Received: June 14, 2015
Last Updated: December 29, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by 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
Naltrexone
Methylnaltrexone
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anticonvulsants
Narcotic Antagonists

ClinicalTrials.gov processed this record on August 22, 2016