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

• Published in: Pain medicine (Malden, Mass.) Vol. 17; no. 6; pp. 1112 - 1130
• Main Authors: Webster, Lynn R., Kopecky, Ernest A., Smith, Michael D., Fleming, Alison B.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2016
• Subjects: Administration, Intranasal; Adult; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacokinetics; Clinical trials; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Double-blind studies; Drug abuse; Drug discrimination; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders - prevention & control; Opioids; OPIOIDS, SUBSTANCE ABUSE & ADDICTIONS SECTION; Oxycodone; Oxycodone - administration & dosage; Oxycodone - pharmacokinetics; Pharmacodynamics; Pharmacokinetics; Young Adult; Extended-Release Opioid; Intranasal; DETERx; Oxycodone; Pharmacodynamic; Abuse-Liability; Abuse-Deterrent; Pharmacokinetic
• ISSN: 1526-2375; 1526-4637
• DOI: 10.1093/pm/pnv020

Abstract Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. 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. Results. 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. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested.