A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Human Abuse Potential Study of Oxycodone ARIR, a Novel, Immediate-Release, Abuse-Deterrent Formulation

• Published in: Pain medicine (Malden, Mass.) Vol. 20; no. 4; pp. 747 - 757
• Main Authors: Webster, Lynn R, Iverson, Matthew, Pantaleon, Carmela, Smith, Michael D, Kinzler, Eric R, Aigner, Stefan
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2019
• Subjects: Central nervous system depressants; Comparative analysis; Double-blind studies; Drug abuse; Evidence-based medicine; Intranasal administration; Narcotics; Opioid abuse; Opioids; OPIOIDS & SUBSTANCE USE DISORDERS SECTION; Oxycodone; Pharmaceutical industry; Pharmacodynamics; Pharmacokinetics; Public health; Public health movements; United States; New Jersey; Opioid; Drug Liking; Intranasal; Oxycodone; Abuse-Deterrent
• ISSN: 1526-2375; 1526-4637
• DOI: 10.1093/pm/pny043

Abstract Objective Prescription opioid abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral abuse. Design This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. Outcome Measures Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. Results Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. Conclusions These data indicate that oxycodone ARIR has the potential to reduce abuse via the intranasal route.