The balance between the
pain relief provided by
opioid analgesics and the side effects caused by such agents is of particular significance to patients who take
opioids for the long-term relief of non-
cancer pain. The spectrum of signs and symptoms affecting the gastrointestinal (GI) tract associated with
opioid use is known as
opioid-induced bowel dysfunction.
Alvimopan is an orally administered, systemically available, peripherally acting
mu-opioid receptor (PAM-OR) antagonist, approved in the US for the management of postoperative
ileus in patients undergoing bowel resection (short-term, in-hospital use only).
Alvimopan was under clinical development for long-term treatment of
opioid-induced constipation (OIC) but this program has been discontinued. This double-blind, placebo-controlled trial, part of the former OIC development program, enrolled patients (N = 485) receiving
opioids for non-
cancer pain. Patients 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 who experienced ≥ 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. There were greater proportions of SBM responders in both
alvimopan treatment groups (63% in both groups) compared with placebo (56%), although these differences were not statistically significant. Secondary efficacy analyses indicated that
alvimopan was numerically superior to placebo in improving
opioid-induced bowel dysfunction symptoms and patients' global assessment of
opioid-induced bowel dysfunction, and reduced the requirement for rescue laxatives. Active treatment was well tolerated and
alvimopan did not antagonize
opioid analgesia.
PERSPECTIVE: Although the primary endpoint was not met in this study, the magnitude of
alvimopan-induced improvements versus baseline, together with previous study results, suggest that a PAM-OR antagonist has the potential to improve OIC.