A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy. STUDY DESIGN: Women (n = 519) were randomized (4:1) to receive alvimopan 12 mg (n = 413) or placebo (n = 106) > or = 2 hours before the operation then twice daily for 7 days (hospital and home). Adverse events were monitored up to 30 days after the last dose of study drug was administered. Efficacy was assessed for 7 postoperative days. RESULTS: Overall, the most common adverse events were nausea, vomiting, and constipation; < 5% of patients discontinued use because of adverse events. Alvimopan significantly accelerated the time to first bowel movement (hazard ratio, 2.33; P <.001). Average time to first bowel movement was reduced by 22 hours, with more frequent bowel movement and better bowel movement quality found in the treatment cohort. CONCLUSION: Alvimopan has a safety profile that is similar to that of placebo and provides significantly improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy.