Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01004393
• Other study ID #: VCC 0911
• Secondary ID: VCC 0911
• Status: Completed
• Phase: Phase 2
• First received: October 28, 2009
• Last updated: December 29, 2015
• Start date: October 2009
• Est. completion date: December 2013

Study information

• Verified date: December 2015
• Source: University of Vermont
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Constipation
• Neoplasms
• Opioid-Related Disorders

Intervention

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

Locations

Country	Name	City	State
United States	Fletcher Allen Health Care	Burlington	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
University of Vermont

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone		4 hours after the dose of subcutaneous methylnaltrexone	No
Secondary	Laxation After Administration of Subcutaneous Methylnaltrexone		24 and 48 hours after the dose of subcutaneous methylnaltrexone	No
Secondary	Time to Laxation After Administration of Subcutaneous Methylnaltrexone		48 hours after the dose of subcutaneous methylnaltrexone	No
Secondary	Overall Pain Scores (0-10; 0=no Pain, 10=Worst Pain) After Administration of Subcutaneous Methylnaltrexone		48 hours after the dose of subcutaneous methylnaltrexone	Yes
Secondary	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		48 hours after the dose of subcutaneous methylnaltrexone	Yes
Secondary	Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone		48 hours after the dose of subcutaneous methylnaltrexone	No
Secondary	Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone		48 hours after the dose of subcutaneous methylnaltrexone	Yes
Secondary	Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone		48 hours after the dose of subcutaneous methylnaltrexone	No