title: Abuse Potential Study of ALO-02 (Extended-Release Oxycodone Surrounding Sequestered Naltrexone) Compared with Immediate-Release Oxycodone Administered Orally to Nondependent Recreational Opioid Users.
abstract: To evaluate the abuse potential of ALO-02, an abuse-deterrent formulation comprising pellets of extended-release oxycodone hydrochloride surrounding sequestered naltrexone hydrochloride.
  
  
  
  Randomized, double-blind, placebo-/active-controlled, 6-way crossover study, with naloxone challenge, drug discrimination, and treatment phases.
  
  
  
  Nondependent, recreational opioid users.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Global Product Development, Global Innovative Pharma - Neuroscience & Pain, Pfizer Inc, Durham, NC, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Setnik
authors.affiliation: Global Product Development, Global Innovative Pharma - Clinical Sciences, Pfizer Inc, Durham, NC, USA.
authors.forename: Almasa
authors.initials: A
authors.lastname: Bass
authors.affiliation: Global Product Development, Global Innovative Pharma - Clinical Sciences, Pfizer Inc, Groton, CT, USA.
authors.forename: Candace
authors.initials: C
authors.lastname: Bramson
authors.affiliation: Early Phase, INC Research LLC, Toronto, Ontario, Canada.
authors.forename: Naama
authors.initials: N
authors.lastname: Levy-Cooperman
authors.affiliation: Global Product Development, Global Innovative Pharma - Clinical Pharmacology, Pfizer Inc, New York, NY, USA.
authors.forename: Bimal
authors.initials: B
authors.lastname: Malhotra
authors.affiliation: Global Product Development, Global Innovative Pharma - Statistics, Pfizer Inc., Collegeville, PA, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Matschke
authors.affiliation: Early Phase, INC Research LLC, Toronto, Ontario, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geoffroy
authors.affiliation: Global Product Development, Global Innovative Pharma - Neuroscience & Pain, Pfizer Inc, Durham, NC, USA.|Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.affiliation: Global Product Development, Global Innovative Pharma - Neuroscience & Pain, Pfizer Inc, Durham, NC, USA.
authors.forename: Gernot
authors.initials: G
authors.lastname: Wolfram
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D013287:Illicit Drugs / Q000097:blood; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000097:blood; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000097:blood; D009293:Opioid-Related Disorders / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D010098:Oxycodone / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013287:Illicit Drugs; D009292:Narcotic Antagonists; D009270:Naloxone; D010098:Oxycodone
keywords: ALO-02; Abuse Deterrent; Abuse Potential; Opioids; Oxycodone