A Randomized, Placebo-Controlled Phase 3 Trial (Study SB-767905/012) of Alvimopan for Opioid-Induced Bowel Dysfunction in Patients With Non-Cancer Pain

Abstract Gastrointestinal (GI) side effects are common with opioid medication, and constipation affects ∼40% of patients. Such symptoms considerably impair patients' quality of life. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist approved in the US for short-term, in-hospital management of postoperative ileus in patients undergoing bowel resection. This double-blind, placebo-controlled trial was conducted as part of a recently discontinued clinical program, in which alvimopan was being developed for opioid-induced constipation (OIC). Patients (N = 518) receiving opioids for non-cancer pain were randomized to receive alvimopan .5 mg once daily, alvimopan .5 mg twice daily, or placebo for 12 weeks. The primary efficacy endpoint was the proportion of patients experiencing ≥3 spontaneous bowel movements (SBMs; bowel movements with no laxative use in the previous 24 hours) per week over the treatment period and an average increase from baseline of ≥1 SBM per week. A significantly greater proportion of patients in the alvimopan .5 mg twice-daily group met the primary endpoint compared with placebo (72% versus 48%, P P Perspective These results demonstrate the potential for a PAM-OR antagonist to improve the symptoms of OIC without antagonizing opioid analgesia.