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Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

Primary Purpose

Neoplasms, Constipation, Opioid-Related Disorders

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Methylnaltrexone bromide

About this trial

This is an interventional supportive care trial for Neoplasms focused on measuring Methylnaltrexone, Constipation, Narcotic Antagonists, Analgesics, Opioid, Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fletcher Allen Health Care

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Methylnaltrexone bromide

Arm Description

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.

Outcomes

Primary Outcome Measures

Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone

Secondary Outcome Measures

Laxation After Administration of Subcutaneous Methylnaltrexone

Time to Laxation After Administration of Subcutaneous Methylnaltrexone

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

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

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

Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone

Full Information

NCT ID

NCT01004393

First Posted

October 28, 2009

Last Updated

December 29, 2015

Sponsor

University of Vermont

1. Study Identification

Unique Protocol Identification Number

NCT01004393

Brief Title

Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Vermont

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neoplasms, Constipation, Opioid-Related Disorders

Keywords

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

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Methylnaltrexone bromide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Methylnaltrexone bromide

Other Intervention Name(s)

Relistor

Intervention Description

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

Primary Outcome Measure Information:

Title

Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone

Time Frame

4 hours after the dose of subcutaneous methylnaltrexone

Secondary Outcome Measure Information:

Title

Laxation After Administration of Subcutaneous Methylnaltrexone

Time Frame

24 and 48 hours after the dose of subcutaneous methylnaltrexone

Title

Time to Laxation After Administration of Subcutaneous Methylnaltrexone

Time Frame