title: Intranasal administration of crushed ALO-02 (extended-release oxycodone with sequestered naltrexone): A randomized, controlled abuse-potential study in nondependent recreational opioid users.
abstract: ALO-02 is an abuse-deterrent formulation consisting of capsules filled with pellets of extended-release oxycodone surrounding sequestered naltrexone. This randomized, double-blind, placebo-/active-controlled, 4-way crossover study examined the abuse potential of crushed ALO-02 administered intranasally to healthy, nondependent, recreational opioid users. Following drug discrimination and naloxone challenge, eligible participants (n = 32) entered a 4-way crossover treatment phase: crushed single dose of 1 of 2 placebos, ALO-02 30 mg/3.6 mg (oxycodone/naltrexone) or oxycodone immediate-release (IR) 30 mg. Primary end points were Drug Liking and High, measured on visual analog scales (VAS) summarized as maximum effect (Emax ) and effect occurring over 2 hours postdose (AUE0-2  h ). Crushed ALO-02 resulted in significantly lower scores versus oxycodone IR on Drug Liking (Emax , 60.5 vs 92.8; AUE0-2  h , 105.4 vs 160.0, respectively) and High (Emax , 25.2 vs 86.9; AUE0-2  h , 27.1 vs 136.4, respectively; n = 28; P < .0001). Adverse events occurred most frequently with oxycodone IR, followed by ALO-02, then placebo, and were considered mild and consistent with opioid therapy. Crushed ALO-02 administered intranasally to nondependent recreational opioid users resulted in significantly lower scores on Drug Liking/High VAS and other positive subjective measures versus crushed oxycodone IR, suggesting less abuse potential. Demonstration of actual abuse deterrence in the real world requires further research.
authors.affiliation: Pfizer Inc, Durham, NC, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Setnik
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Candace
authors.initials: C
authors.lastname: Bramson
authors.affiliation: Pfizer Inc, Durham, NC, USA.
authors.forename: Almasa
authors.initials: A
authors.lastname: Bass
authors.affiliation: INC Research, LLC, Toronto, ON, Canada.
authors.forename: Naama
authors.initials: N
authors.lastname: Levy-Cooperman
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Bimal
authors.initials: B
authors.lastname: Malhotra
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Matschke
authors.affiliation: Pfizer Inc, Durham, NC, USA.|Duke University Medical Center, Durham, NC, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.affiliation: Pfizer Inc, Durham, NC, USA.
authors.forename: Gernot
authors.initials: G
authors.lastname: Wolfram
authors.affiliation: INC Research, LLC, Toronto, ON, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geoffroy
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004338:Drug Combinations; D055030:Drug Users / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D017060:Patient Satisfaction; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; C000608978:oxycodone naltrexone combination; D009271:Naltrexone; D010098:Oxycodone
keywords: ALO-02; abuse deterrent; abuse potential; opioids; pharmacodynamic