title: Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study.
abstract: BACKGROUND
  Tapentadol is a novel, centrally acting analgesic with mu-opioid receptor agonist and norepinephrine reuptake inhibitor activity.
  
  
  OBJECTIVE
  to evaluate the efficacy and safety of Tapentadol extended release (ER) compared with oxycodone controlled release (CR) for management of moderate to severe chronic osteoarthritis-related knee pain.
  
  
  METHODS
  this was a randomized, double-blind, active- and placebo-controlled, parallel-arm, multicentre, phase III study during which patients received Tapentadol ER, oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period. The study was carried out at sites in Australia, Canada, New Zealand and the US. A total of 1030 patients with chronic osteoarthritis-related knee pain were randomized to receive Tapentadol ER 100-250 mg twice daily, oxycodone HCl CR 20-50 mg twice daily or placebo. Primary endpoints (as determined prior to initiation of the study) were the changes from baseline in average daily pain intensity (rated by patients on an 11-point numerical rating scale) over the last week of maintenance and over the entire 12-week maintenance period; last observation carried forward was used to impute missing values after early treatment discontinuation.
  
  
  RESULTS
  efficacy and safety were evaluated for 1023 patients. Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95% CI], -0.7 [-1.04, -0.33]), and throughout the maintenance period (-0.7 [-1.00, -0.33]). Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95% CI], -0.3 [-0.67, -0.00]) but not at week 12 (-0.3 [-0.68, 0.02]). A significantly higher percentage of patients achieved > or =50% improvement in pain intensity in the Tapentadol ER group (32.0% [110/344]) compared with the placebo group (24.3% [82/337]; p = 0.027), indicating a clinically significant improvement in pain intensity, while a significantly lower percentage of patients achieved > or =50% improvement in pain intensity in the oxycodone CR group (17.3% [59/342]; p = 0.023 vs placebo). In the placebo, Tapentadol ER and oxycodone CR groups, respectively, 61.1% (206/337), 75.9% (261/344) and 87.4% (299/342) of patients reported at least one treatment-emergent adverse event (TEAE); incidences of gastrointestinal-related TEAEs were 26.1% (88/337), 43.0% (148/344) and 67.3% (230/342).
  
  
  CONCLUSIONS
  treatment with Tapentadol ER 100-250 mg twice daily or oxycodone HCl CR 20-50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain, with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with Tapentadol ER than with oxycodone CR.
authors.affiliation: Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Afilalo
authors.forename: Mila S
authors.initials: MS
authors.lastname: Etropolski
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kuperwasser
authors.forename: Kathy
authors.initials: K
authors.lastname: Kelly
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Ilse
authors.initials: I
authors.lastname: Van Hove
authors.forename: Achim
authors.initials: A
authors.lastname: Steup
authors.forename: Bernd
authors.initials: B
authors.lastname: Lange
authors.forename: Christine
authors.initials: C
authors.lastname: Rauschkolb
authors.forename: Juergen
authors.initials: J
authors.lastname: Haeussler
mesh_terms: D000368:Aged; D000700:Analgesics / Q000008:administration & dosage*; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy*; D010636:Phenols / Q000008:administration & dosage* / Q000009:adverse effects; D000077432:Tapentadol
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D010636:Phenols; D010098:Oxycodone; D000077432:Tapentadol