Study Evaluating Subcutaneous Methylnaltrexone For Treatment Of Opioid-Induced Constipation In Patients With Advanced Illness

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of methylnaltrexone administered as subcutaneous injections in subjects who have opioid-induced constipation and an advanced illness. The hypothesis is that methylnaltrexone will be safe and effective in relieving opioid-induced constipation in these subjects.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study Of A Fixed Dose Of Subcutaneous Methylnaltrexone In Adults With Advanced Illness And Opioid-Induced Constipation: Efficacy, Safety, And Additional Health Outcomes

Conditions
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Opioid-Induced Constipation

Intervention / Treatment
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* Drug: Methylnaltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is an adult 18 years of age or older Has a diagnosis of advanced illness (ie, a terminal illness such as incurable cancer or other end-stage disease) Has a life expectancy of at least 1 month. Is receiving opioids on a regular schedule (not just as-needed or rescue doses) for the control of pain or discomfort for at least 2 weeks before the first dose of study drug. Has constipation that is caused by opioid medications. Exclusion Criteria: Has a known or suspected allergy to methylnaltrexone or other similar compounds (e.g. naltrexone or naloxone). Has a known or suspected mechanical gastrointestinal obstruction. Has any potential nonopioid cause of bowel dysfunction that might be a major contributor to the constipation. Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study. Receiving opioid antagonist or partial antagonist products.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylnaltrexone<br>Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses). Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; or 0.4 mL (8 mg) every other day if weight between 38 and <62 kg. Subjects with impaired kidney function received reduced doses according to instructions in the Relistor prescribing information. | Drug: Methylnaltrexone<br> <br> * Other names: Relistor;|
| Placebo Comparator: Placebo<br>Placebo subcutaneously every other day for 14 days (ie, 7 doses). Subjects received 0.6 mL every other day if weight ≥ 62kg; or 0.4 mL every other day if weight between 38 and < 62 kg. Subjects with impaired kidney function received reduced volumes of placebo solution to match the volumes used in the experimental group. | Drug: Placebo<br> <br> * Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses | This outcome measures the proportion of subjects who had a rescue-free laxation (ie, bowel movement) within 4 hours after at least 2 of the first 4 doses of study drug. A rescue free laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Rescue-free Laxation (Following the First Dose of Study Drug). | This outcome measures the time from first dose of study drug to the first rescue-free laxation (ie, bowel movement). A rescue free laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation. | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid-induced constipation