Randomized, Double‐Blind Trial of Oral Methylnaltrexone for the Treatment of Opioid‐Induced Constipation in Patients with Chronic Noncancer Pain. Issue 6 (10th February 2017)

• Record Type: Journal Article
• Authors: Rauck, Richard; Slatkin, Neal E.; Stambler, Nancy; Harper, Joseph R.; Israel, Robert J.
• Is Part Of: Pain practice. Volume 17:Issue 6(2017:Jul.)
• Page Start: 820
• Page End: 828
• Publication Date: 2017-02-10
• Subjects: methylnaltrexone -- noncancer pain -- oral -- opioid‐induced constipation -- Relistor -- μ‐opioid receptor antagonist; Pain -- Treatment -- Periodicals; 616.0472
• DOI: 10.1111/papr.12535
• Languages: English
• ISSNs: 1530-7085

Abstract

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.