• Lynn R Webster, Ernest A Kopecky, Michael D Smith, and Alison B Fleming.
• *Early Development Services, Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah, USA; WebsterLynn@prahs.com.
• Pain Med. 2016 Jun 1; 17 (6): 111211301112-30.

ObjectiveEvaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein "DETERx").DesignRandomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study.SettingClinical research site.SubjectsThere were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods.MethodsThe 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.ResultsFor 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.ConclusionsPharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested.© 2015 American Academy of Pain Medicine.

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