Abstract
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.
Key words
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Article info
Publication history
Accepted:
June 15,
2010
Received in revised form:
April 23,
2010
Received:
October 8,
2009
Footnotes
This study (SB-767905/013) was funded by GlaxoSmithKline (GSK). Funding for medical editorial assistance for this manuscript was provided by Adolor Corporation, Exton, Pennsylvania, and GSK, Philadelphia, Pennsylvania.
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
