Abuse Potential Study of ALO-02 (Extended-Release Oxycodone Surrounding Sequestered Naltrexone) Compared with Immediate-Release Oxycodone Administered Orally to Nondependent Recreational Opioid Users

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-/active-controlled, 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 (E(max)) and area-under-the-effect-curve from 0 to 2 hours (AUE(0-2h)). Other pharmacodynamic, pharmacokinetic and safety assessments were included. Results. Drug Liking and High (E(max)) for crushed oxycodone IR 40 mg were significantly higher compared with placebo, confirming study validity (P < 0.0001). Drug Liking and High (E(max,) AUE(0-2h)) for crushed ALO-02 (40 mg/4.8 mg and 60 mg/7.2 mg) were significantly lower compared to corresponding doses of crushed oxycodone IR (40 and 60 mg; P < 0.0001). Likewise, Drug Liking and High (E(max) and AUE(0-2h)) for intact ALO-02 60 mg/7.2 mg were significantly lower compared with crushed oxycodone IR 60 mg (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.