title: Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (Oxecta™) tablets in nondependent recreational opioid users.
abstract: OBJECTIVE
  To evaluate the pharmacodynamic effects (subjective and physiologic) of a new formulation of immediate release oxycodone HCl (IRO-A; Oxecta™) tablets compared with immediate release oxycodone HCl (IRO; Roxicodone®) tablets when crushed and administered intranasally to nondependent recreational opioid users.
  
  
  METHODS
  Single-center, single-dose, randomized, double-blind, active-controlled two-way crossover study.
  
  
  METHODS
  Inpatient Clinical Pharmacology Unit, Toronto, Canada.
  
  
  METHODS
  Nondependent, recreational opioid users aged 18-55 years.
  
  
  METHODS
  Subjects able to discriminate intranasally administered crushed IRO from placebo were randomized to receive 15 mg crushed IRO-A and crushed IRO in crossover fashion in treatment phase.
  
  
  METHODS
  Primary subjective endpoints were maximum effect (E(max)) for Drug Liking and effect at 8 hours (E(8h)) postdose for Take Drug Again and Overall Drug Liking. All were assessed using bipolar 0-100 visual analog scale (VAS; 50 points = neutral). Secondary pharmacodynamic endpoints included other VAS endpoints, pupillometry, and subject-rated scales for nasal effects.
  
  
  RESULTS
  Forty subjects were randomized to treatment; 39 were evaluable, one subject was excluded for postdose vomiting. Subjects were mostly male (80 percent) and White (75 percent). Least squares mean Drug Liking VAS E(max) (70.8 vs 93.5), Overall Drug Liking E(8h) (47.8 vs 87.4), and Take Drug Again E(8h) (45.9 vs 91.3) were significantly lower for crushed IRO-A vs IRO (all p < 0.0001). A significant sequence effect was found, but lower liking of IRO-A was observed for both treatment sequence groups. Pupillary responses between treatments were similar overall, but differences were noted for some endpoints/time points. Adverse events common to opioids were observed with both treatments. Subjects experienced more nasal-related symptoms with IRO-A.
  
  
  CONCLUSIONS
  Crushed IRO-A tablets demonstrated lower scores on "drug liking," "overall drug liking," and "take drug again" than crushed IRO when administered intranasally to nondependent recreational opioid users.
authors.affiliation: INC Research, Toronto, Ontario, Canada.
authors.forename: Kerri A
authors.initials: KA
authors.lastname: Schoedel
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rolleri
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Faulknor
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Pixton
authors.forename: Nancy
authors.initials: N
authors.lastname: Chen
authors.forename: Almasa
authors.initials: A
authors.lastname: Bass
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.forename: Edward
authors.initials: E
authors.lastname: Sellers
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage*; D011680:Pupil / Q000187:drug effects; D013607:Tablets
chemical_list: D000701:Analgesics, Opioid; D013287:Illicit Drugs; D013607:Tablets; D010098:Oxycodone