• Beatrice Setnik, Almasa Bass, Candace Bramson, Naama Levy-Cooperman, Bimal Malhotra, Kyle Matschke, Pierre Geoffroy, Kenneth W Sommerville, and Gernot Wolfram.
• Global Product Development, Global Innovative Pharma - Neuroscience & Pain, Pfizer Inc, Durham, NC, USA.
• Pain Med. 2017 Jun 1; 18 (6): 1077-1088.

ObjectiveTo evaluate the abuse potential of ALO-02, an abuse-deterrent formulation comprising pellets of extended-release oxycodone hydrochloride surrounding sequestered naltrexone hydrochloride.DesignRandomized, double-blind, placebo-/active-controlled, 6-way crossover study, with naloxone challenge, drug discrimination, and treatment phases.SubjectsNondependent, recreational opioid users.MethodsOral 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.ResultsDrug 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.ConclusionsThe results suggest that ALO-02 (crushed or intact) has lower abuse potential than crushed oxycodone IR when administered orally in nondependent, recreational opioid users.© 2016 American Academy of Pain Medicine.

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