title: A randomized, placebo-controlled phase 3 trial (Study SB-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Swedish Medical Center, Seattle, Washington 98104, USA. gordon.irving@swedish.org
authors.forename: Gordon
authors.initials: G
authors.lastname: Irving
authors.forename: Janos
authors.initials: J
authors.lastname: Pénzes
authors.forename: Brian
authors.initials: B
authors.lastname: Ramjattan
authors.forename: Michael
authors.initials: M
authors.lastname: Cousins
authors.forename: Richard
authors.initials: R
authors.lastname: Rauck
authors.forename: Egilius L H
authors.initials: EL
authors.lastname: Spierings
authors.forename: Christi S
authors.initials: CS
authors.lastname: Kleoudis
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Snidow
authors.forename: Amy
authors.initials: A
authors.lastname: Pierce
authors.forename: John
authors.initials: J
authors.lastname: Wurzelmann
authors.forename: Eric R
authors.initials: ER
authors.lastname: Mortensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; D010919:Placebos; C419502:alvimopan