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

Abstract

ALO-02 consists of capsules filled with pellets that contain extended-release oxycodone hydrochloride surrounding sequestered naltrexone hydrochloride and is designed to deter abuse. The abuse potential of ALO-02 was compared to immediate-release (IR) oxycodone in a randomized, double-blind, double-dummy, placebo- and active-controlled, 6-way crossover study in non-dependent, recreational opioid users, with naloxone challenge, drug discrimination, and treatment phases. Treatments (≥5 days apart) included placebo, intact and crushed ALO-02 60-mg, crushed IR oxycodone 60-mg, crushed ALO-02 40-mg, and crushed IR oxycodone 40-mg. Drug liking and high visual analog scale (VAS) ratings were primary endpoints with maximum effects (Emax) and effects within 2 hours post-dose (AUE0-2h) as measures of interest. Of the 41 participants [88% male, 81% white, mean age 38 years (21-54)] randomized into treatment phase, 32 received all treatments. Emax for drug liking, high, and take drug again VAS between IR oxycodone 40-mg and placebo were statistically different, confirming study validity. Drug liking Emax for crushed ALO-02 40-mg (70.2) was significantly lower versus IR oxycodone 40-mg (85.5), and for crushed (74.5) and intact (59.3) ALO-02 60-mg versus oxycodone IR 60-mg (89.8; p<0.0001 for comparisons). AUE0-2h for drug liking, as well as Emax and AUE0-2 for high, were also significantly lower for the ALO-02 doses versus corresponding IR oxycodone doses (p<0.0001). These measures for both endpoints were significantly greater for both doses of crushed ALO-02 versus placebo. Fewer subjects experienced adverse events (AEs) after crushed ALO-02 60-mg (91.9%), intact ALO-02 60-mg (71.1%), and crushed ALO-02 40-mg (80.6%) compared with crushed oxycodone IR (40-mg and 60-mg: 100%). The most common AEs with crushed ALO-02 and oxycodone IR were euphoric mood, somnolence, pruritus, and dizziness. These results support that oral ALO-02 (crushed or intact) in non-dependent, recreational opioid users has significantly lower abuse potential than crushed IR oxycodone. Sponsored by Pfizer Inc.