Pain medicine (Malden, Mass.) · 2017
Abuse Potential Study of ALO-02 (Extended-Release Oxycodone Surrounding Sequestered Naltrexone) Compared with Immediate-Release Oxycodone Administered Orally to Nondependent Recreational Opioid Users.
Сравнительное исследованиеСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Setnik Beatrice, Bass Almasa, Bramson Candace, Levy-Cooperman Naama, Malhotra Bimal, Matschke Kyle, Geoffroy Pierre, Sommerville Kenneth W, Wolfram Gernot
Аннотация
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.
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.