title: Comparison of subjective effects of extended-release versus immediate-release oxycodone/acetaminophen tablets in healthy nondependent recreational users of prescription opioids: a randomized trial.
abstract: BACKGROUND
  Prescription opioids have substantial abuse potential. This study compared the positive subjective drug effects of a newly developed extended-release (ER) oxycodone (OC)/acetaminophen (acetyl-para-aminophenol [APAP]) formulation with those of immediate-release (IR) OC/APAP.
  
  
  METHODS
  This randomized, double-blind, active- and placebo-controlled, 7-way crossover study enrolled healthy volunteers who were recreational prescription opioid users. The protocol was approved by an institutional review board and all participants provided written informed consent. Participants received single doses of intact ER and IR OC/APAP 15/650 mg, intact ER and IR OC/APAP 30/1300 mg, crushed ER and IR OC/APAP 30/1300 mg, and placebo. Peak subjective effects (Emax), time to Emax, and area under the drug-effect curves for drug liking, drug high, and good drug effects were measured using visual analogue scales. Least squares means with 95% confidence interval were compared using analysis of variance.
  
  
  RESULTS
  Among completers (N = 55), intact ER OC/APAP produced delayed and lower peak effects versus IR OC/APAP. Comparing intact tablets, the drug liking Emax (least squares means [95% confidence interval]) was significantly lower for OC/APAP 30/1300 mg (76.4 [72.8 to 80.0]) than for IR OC/APAP 30/1300 mg (85.6 [81.9 to 89.2]; difference, -9.2 [-13.1 to -5.2]; P < 0.001). Similar results were observed for intact ER and IR OC/APAP (15 mg/650 mg). Crushing ER OC/APAP 30/1300 mg further delayed these effects compared with the same dose of crushed IR OC/APAP and intact ER OC/APAP.
  
  
  CONCLUSIONS
  Extended-release OC/APAP produced lower subjective drug effects than IR OC/APAP. Crushing ER OC/APAP further delayed onset of subjective effects compared with intact ER OC/APAP. The ER OC/APAP may be less attractive for abuse than IR OC/APAP.
  
  
  BACKGROUND
  This phase 1 study conducted in the United States was not registered.
authors.affiliation: Senior Principal Pharmacokinetic Scientist, PRA Healthsciences, Salt Lake City, UT.
authors.forename: Terri
authors.initials: T
authors.lastname: Morton
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kostenbader
authors.forename: Jeannie
authors.initials: J
authors.lastname: Montgomery
authors.forename: Krishna
authors.initials: K
authors.lastname: Devarakonda
authors.forename: Thomas
authors.initials: T
authors.lastname: Barrett
authors.forename: Lynn
authors.initials: L
authors.lastname: Webster
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage*; D013607:Tablets; D055815:Young Adult
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D013607:Tablets; C514822:oxycodone-acetaminophen; D000082:Acetaminophen; D010098:Oxycodone