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 < .001). Treatment with
alvimopan twice daily improved a number of other symptoms compared with placebo and reduced the requirement for rescue
laxative use. The
opioid-induced bowel dysfunction Symptoms Improvement Scale (SIS) responder rate was 40.4% in the
alvimopan .5 mg twice daily group, versus 18.6% with placebo (P < .001). In general,
alvimopan .5 mg once daily produced qualitatively similar but numerically smaller responses than twice-daily treatment. Active treatment did not increase the requirement for
opioid medication or increase average
pain intensity scores. Over the 12-week treatment period,
alvimopan appeared to be well tolerated.
PERSPECTIVE: