title: Dose equivalence of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone: a randomized, double-blind trial incorporating a measure of assay sensitivity.
abstract: Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent. This trial evaluated dose equivalence using a measure of assay sensitivity. Patients were converted to open-label IR hydromorphone, underwent dose titration, and those on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of: 1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy was measured using breakthrough medication use, pain, sleep, and global assessments. Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable effects on all measures. Although the prespecified primary analysis of the difference in total daily dose of breakthrough medication between the full-dose ER and half-dose ER groups was not significant, more patients in the half-dose ER group required an increase in breakthrough medication (P = .026) and the half-dose ER group both increased the number of breakthrough doses (P = .026) and had greater percent change in the total daily dose of breakthrough medication (P = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone at the same daily dose provides equivalent analgesia.
  
  
  CONCLUSIONS
  In a randomized, double-blind trial, the same total daily dose of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had comparable effects. Detection of different effects between blinded dose levels was used as a measure of assay sensitivity. The measure of assay sensitivity can enhance the interpretation of dose equivalence or noninferiority trials.
authors.affiliation: Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY 10003, USA. rcruciani@chpnet.org
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Cruciani
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Katz
authors.forename: Russell K
authors.initials: RK
authors.lastname: Portenoy
mesh_terms: D000328:Adult; D000368:Aged; D000698:Analgesia / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D059390:Breakthrough Pain / Q000188:drug therapy* / Q000517:prevention & control; D059350:Chronic Pain / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D018579:Patient Selection
chemical_list: D000701:Analgesics, Opioid; D004091:Hydromorphone