Long-Term Safety and Efficacy of Subcutaneous Methylnaltrexone in Patients with Opioid-Induced Constipation and Chronic Noncancer Pain: A Phase 3, Open-Label Trial

Abstract

OBJECTIVE: Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, alleviates opioid-induced constipation. Understanding its long-term safety and efficacy profile in patients with chronic noncancer pain is warranted given the persistence of opioid-induced constipation. METHODS.: In this phase 3, multicenter, open-label trial, adults with chronic noncancer pain (N = 1034) received subcutaneous methylnaltrexone 12 mg once daily for 48 weeks. RESULTS: The most common adverse events were gastrointestinal related (e.g., abdominal pain, diarrhea, nausea) and were mild to moderate in intensity. Only 15.2% of patients discontinued because of an adverse event. Serious cardiac-related adverse events occurred in nine patients. Of the seven instances of major adverse coronary events reported, three were adjudicated after external review; all instances occurred in patients with cardiovascular risk factors. Methylnaltrexone elicited a bowel movement within four hours in 34.1% of the injections throughout the 48-week treatment period. CONCLUSIONS: Change from baseline in mean weekly bowel movement rate, Bowel Movement Straining Scale score, Bristol Stool Scale score, and mean percentage of patients with complete evacuation from baseline to week 48 were significantly improved ( P < 0.001 for all). Long-term subcutaneous methylnaltrexone was well tolerated, with no new safety concerns, and provided consistent opioid-induced constipation relief in patients with chronic noncancer pain.