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Original Report| Volume 12, ISSUE 2, P185-193, February 2011

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

DOI:https://doi.org/10.1016/j.jpain.2010.06.012
A Randomized, Placebo-Controlled Phase 3 Trial (Study SB-767905/012) of Alvimopan for Opioid-Induced Bowel Dysfunction in Patients With Non-Cancer Pain
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      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 < .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

      These results demonstrate the potential for a PAM-OR antagonist to improve the symptoms of OIC without antagonizing opioid analgesia.

      Key words

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      Article info

      Publication history

      Accepted: June 19, 2010
      Received in revised form: April 23, 2010
      Received: October 9, 2009

      Footnotes

      Supported by GlaxoSmithKline (GSK). Funding for medical editorial assistance for this manuscript was provided by Adolor Corporation, Exton, Pennsylvania, and GlaxoSmithKline, Philadelphia, Pennsylvania.

      Identification

      DOI: https://doi.org/10.1016/j.jpain.2010.06.012

      Copyright

      © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

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