title: Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory crossover study.
abstract: BACKGROUND
  Recently, a new oral prolonged-release formulation of morphine sulfate for once-daily dosing has been developed based on an injection-molded matrix (abuse-deterrent, prolonged-release erodible matrix [ADPREM]).
  
  
  OBJECTIVE
  The objective of this double-blind, randomized, exploratory crossover study was to assess the efficacy and safety of once-daily ADPREM compared with twice-daily controlled-release morphine (CRM; MST ContinusNapp Pharmaceuticals, Cambridge, UK).
  
  
  METHODS
  Thirty-eight adult cancer pain patients participated in the study, which consisted of a run-in period for stabilization and two consecutive fixed-dose treatment periods of two weeks' duration each. Rescue medication, immediate-release morphine sulfate, was available during the entire study for treatment of breakthrough pain (BTP).
  
  
  RESULTS
  There was no difference between the treatments in use of rescue medication. The medians of the average number of rescue doses per day were 1.0 and 0.7 during the ADPREM and CRM treatment periods, respectively, with an estimated median difference of 0.07 dose/day (95% confidence interval: -0.21, 0.29). Likewise, no differences between treatments were found for the number of BTP episodes per day or morning and evening ratings of pain intensity (current, average, minimum, and maximum). Median assessment of the drugs was "good" for both treatments, and neither of the treatments was preferred. Steady-state trough concentrations of morphine and its metabolites in plasma before morning dosing were similar after either treatment period. The adverse events were as expected in an opioid-treated cancer population and showed no differences between ADPREM and CRM.
  
  
  CONCLUSIONS
  In this study, dosing with ADPREM at intervals of 24 hours was therapeutically equivalent to CRM dosed at intervals of 12 hours.
authors.affiliation: SRA International, Merced, California, USA.
authors.forename: Derry
authors.initials: D
authors.lastname: Ridgway
authors.forename: Maciej
authors.initials: M
authors.lastname: Sopata
authors.forename: Arvydas
authors.initials: A
authors.lastname: Burneckis
authors.forename: Lillian
authors.initials: L
authors.lastname: Jespersen
authors.forename: Christine
authors.initials: C
authors.lastname: Andersen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009020:Morphine