title: Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives.
abstract: OBJECTIVE
  The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated in patients with moderate-to-severe chronic cancer-related or non-cancer pain. All patients had opioid-induced constipation (OIC) which persisted despite substantial laxative therapy.
  
  
  METHODS
  This pooled analysis included 75 patients with OIC at study entry that was refractory to at least two laxatives with different modes of action. Patients completed randomized, double-blind treatment with OXN PR 20-120 mg/day for either 12 weeks (OXN 9001: non-cancer pain study) or 4 weeks (OXN 2001: cancer-related pain study). Analgesia and bowel function were assessed using the Brief Pain Inventory Short Form and Bowel Function Index (BFI), respectively. Use of laxative medication and safety were assessed throughout the studies.
  
  
  BACKGROUND
  NCT00513656, EudraCT 2005-002398-57, EudraCT 2005-003510-15.
  
  
  RESULTS
  Statistically and clinically significant improvements in bowel function were observed following double-blind treatment with OXN PR. Mean (SD) reduction in BFI score was 21.2 (28.8) and comparable in patients with cancer-related (19.0 [28.9]) and non-cancer pain (23.3.[29.0]; P ≤ 0.0002). Furthermore, the proportion of patients with a BFI score within normal range (≤28.8) increased from 9.5% at screening to 43.1% at Day 15 of OXN PR. While all patients used ≥2 laxatives of different classes at screening, during study treatment 36% stopped using laxatives (P < 0.001). OXN PR provided effective analgesia, evidenced by stable pain scores during study treatment, and there were no unanticipated adverse events.
  
  
  CONCLUSIONS
  OXN PR significantly improved bowel function and reduced the use of laxatives in patients with OIC, previously unresponsive to at least two different classes of laxatives. OXN also provided effective analgesia for patients with moderate-to-severe cancer-related pain and non-cancer-related pain.
authors.affiliation: Mundipharma Pharmaceuticals BV, Medical Department , Hoevelaken , The Netherlands.
authors.forename: Gineke
authors.initials: G
authors.lastname: Koopmans
authors.forename: Karen
authors.initials: K
authors.lastname: Simpson
authors.forename: Javier
authors.initials: J
authors.lastname: De Andrés
authors.forename: Eberhard Albert
authors.initials: EA
authors.lastname: Lux
authors.forename: Michel
authors.initials: M
authors.lastname: Wagemans
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Van Megen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D003672:Defecation; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D054368:Laxatives / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications; D010098:Oxycodone / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D054368:Laxatives; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone
keywords: Chronic pain; Constipation; Laxatives; Naloxone; Opioid analgesic; Oxycodone