title: Results of a double-blind, placebo-controlled, fixed-dose assessment of once-daily OROS® hydromorphone ER in patients with moderate to severe pain associated with chronic osteoarthritis.
abstract: OBJECTIVE
  Opioids are recommended for patients with moderate to severe pain due to osteoarthritis (OA), who do not receive adequate analgesia from nonopioid treatment. The objective of this study was to evaluate the efficacy and safety of OROS hydromorphone extended-release (ER) compared with placebo in patients with moderate to severe pain associated with OA.
  
  
  METHODS
  This was a randomized, placebo-controlled, double-blind, fixed-dose study. Patients received placebo or fixed-dose OROS hydromorphone ER (8 or 16 mg). The primary efficacy measure was pain intensity score (11-point Numeric Rating Scale) at Maintenance Week 12, analyzed with baseline observation carried forward (BOCF) imputation for missing data.
  
  
  RESULTS
  This study did not meet the primary efficacy measure using the BOCF imputation. Study discontinuation was high (52%). When analyzed using last observation carried forward (LOCF) imputation, the prespecified alternate method, OROS hydromorphone ER 16 mg provided significantly better analgesia than placebo (P = 0.0009). Treatment was associated with significant improvements in patient global assessment (P = 0.01), the overall Western Ontario and McMaster Osteoarthritis Index (WOMAC) (P = 0.0003), and its subscales: pain (P = 0.0001), stiffness (P = 0.0023), and physical function (P = 0.0006). Gastrointestinal adverse events, such as constipation and nausea, were common among patients receiving OROS hydromorphone ER.
  
  
  CONCLUSIONS
  OROS hydromorphone ER failed to achieve statistical significance for the primary endpoint using the prespecified imputation method (BOCF), likely due to the high discontinuation rate associated with the fixed-dose design. When data were analyzed according to an alternate method of imputation (LOCF), OROS hydromorphone ER demonstrated statistically significant improvements in pain, stiffness, and physical function.
authors.affiliation: Anesthesiology Pain Management, The Carolinas Pain Institute, Winston-Salem, NC 27103, USA. rrauck@ccrpain.com
authors.forename: Richard
authors.initials: R
authors.lastname: Rauck
authors.forename: Ronald
authors.initials: R
authors.lastname: Rapoport
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019370:Observation; D010003:Osteoarthritis / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000175:diagnosis / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D004091:Hydromorphone