Randomized, Double-Blind Trial of Oral Methylnaltrexone for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain.

Abstract

BACKGROUND:

Subcutaneous methylnaltrexone, a peripherally acting μ-opioid receptor antagonist, improves opioid-induced constipation (OIC) in patients with chronic noncancer pain. An oral methylnaltrexone formulation has been developed.

METHODS:

In this phase 3, double-blind trial, adults with chronic noncancer pain receiving opioid doses of ≥ 50 mg/day oral morphine equivalents with OIC were randomly assigned to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily (QD) for 4 weeks followed by as-needed dosing for 8 weeks. Patients who had ≥ 3 rescue-free bowel movements (RFBMs)/week, with an increase of ≥ 1 RFBM/week from baseline for ≥ 3 of 4 weeks during the QD period, were responders.

RESULTS:

Overall, 803 patients were included in the analyses. A significantly greater percentage of patients had an increase in mean percentage of dosing days resulting in an RFBM within 4 hours of dosing during weeks 1 through 4 (QD period; primary endpoint) with methylnaltrexone (300 mg/day [24.6%; P = 0.002] and 450 mg/day [27.4%; P < 0.0001]) vs. placebo (18.2%). The percentage of responders (49.3% for 300 mg [P = 0.03] and 51.5% for 450 mg [P = 0.005] vs. 38.3% with placebo) and change from baseline in mean number of weekly RFBMs (difference vs. placebo, 0.5 for 300 mg [P = 0.03] and 0.5 for 450 mg [P = 0.02]) was significantly greater with methylnaltrexone 300 and 450 mg/day vs. placebo during the QD period. All dosages of oral methylnaltrexone were well tolerated.

CONCLUSIONS:

Oral methylnaltrexone was efficacious and well tolerated for OIC in patients with chronic noncancer pain, particularly the 450-mg dose.

• Authors: Richard Rauck, Neal E Slatkin, Nancy Stambler, Joseph R Harper, Robert J Israel
• Journal: Pain practice : the official journal of World Institute of Pain (Pain Pract) Vol. 17 Issue 6 Pg. 820-828 (07 2017) ISSN: 1533-2500 [Electronic] United States
• PMID: 27860208 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2016 The Authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

Chemical References

• Analgesics, Opioid
• Narcotic Antagonists
• Quaternary Ammonium Compounds
• Receptors, Opioid, mu
• methylnaltrexone
• Naltrexone

Topics

• Administration, Oral
• Adult
• Aged
• Analgesics, Opioid (adverse effects, therapeutic use)
• Chronic Pain (drug therapy, epidemiology)
• Constipation (chemically induced, drug therapy, epidemiology)
• Double-Blind Method
• Female
• Humans
• Injections, Subcutaneous
• Male
• Middle Aged
• Naltrexone (administration & dosage, analogs & derivatives)
• Narcotic Antagonists (administration & dosage)
• Quaternary Ammonium Compounds (administration & dosage)
• Receptors, Opioid, mu (antagonists & inhibitors)
• Treatment Outcome