title: A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone.
abstract: Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein "DETERx").
  
  
  
  Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study.
  
  
  
  Clinical research site.
  
  
  
  There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods.
  
  
  
  The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx-administered as either a crushed intranasal (IN) or an intact oral (PO) preparation-with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control.
  
  
  
  For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated.
  
  
  
  Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested.
authors.affiliation: *Early Development Services, Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah, USA; WebsterLynn@prahs.com.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
authors.affiliation: Clinical Development and.
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Kopecky
authors.affiliation: *Early Development Services, Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah, USA;
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Product Development, Collegium Pharmaceutical Inc., Canton, Massachusetts, USA.
authors.forename: Alison B
authors.initials: AB
authors.lastname: Fleming
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D010098:Oxycodone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010098:Oxycodone
keywords: Abuse-Deterrent; Abuse-Liability; DETERx; Extended-Release Opioid; Intranasal; Oxycodone; Pharmacodynamic; Pharmacokinetic
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