Abuse potential study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) compared with immediate-release oxycodone administered orally to nondependent recreational opioid users

Abstract

Objective. To evaluate the abuse potential of ALO- 02, an abuse-deterrent formulation comprising pellets of extended-release oxycodone hydrochloride surrounding sequestered naltrexone hydrochloride. Design. Randomized, double-blind, placebo-/activecontrolled, 6-way crossover study, with naloxone challenge, drug discrimination, and treatment phases. Subjects. Nondependent, recreational opioid users. Methods. Oral administration of crushed and intact ALO-02, crushed immediate-release (IR) oxycodone, and placebo. Primary endpoints were Drug Liking and High measured on visual analog scales and reported as maximum effect (Emax) and area-under-the-effect-curve from 0 to 2 hours (AUE0-2h). Other pharmacodynamic, pharmacokinetic and safety assessments were included. Results. Drug Liking and High (Emax) for crushed oxycodone IR 40mg were significantly higher compared with placebo, confirming study validity (P < 0.0001). Drug Liking and High (Emax, AUE0-2h) for crushed ALO-02 (40mg/4.8mg and 60 mg/7.2mg) were significantly lower compared to corresponding doses of crushed oxycodone IR (40 and 60mg; P < 0.0001). Likewise, Drug Liking and High (Emax and AUE0-2h) for intact ALO-02 60mg/7.2mg were significantly lower compared with crushed oxycodone IR 60mg (P < 0.0001). Secondary pharmacodynamic endpoints and plasma concentrations of oxycodone and naltrexone were consistent with these results. Fewer participants experienced adverse events (AEs) after ALO-02 (crushed or intact: 71.1-91.9%) compared with crushed oxycodone IR (100%). Most common AEs following crushed ALO-02 and oxycodone IR were euphoric mood, pruritus, somnolence, and dizziness. Conclusions. The results suggest that ALO-02 (crushed or intact) has lower abuse potential than crushed oxycodone IR when administered orally in nondependent, recreational opioid users.