title: Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational opioid users.
abstract: ALO-02, comprising pellets of extended-release oxycodone surrounding sequestered naltrexone, is intended to deter abuse.
  
  
  
  Determine the abuse potential of intravenous oxycodone combined with naltrexone, which represents simulated crushed ALO-02 in solution, compared with intravenous oxycodone in nondependent, recreational opioid users.
  
  
  
  A randomized, double-blind, placebo-controlled, three-way crossover study with naloxone challenge, drug discrimination, and treatment phases. Intravenous treatments included oxycodone hydrochloride 20 mg, oxycodone hydrochloride 20 mg plus naltrexone hydrochloride 2.4 mg (simulated crushed ALO-02 20 mg/2.4 mg), or placebo (0.9% sodium chloride for injection). Primary end points were peak effects (Emax) and area under the effects curve within 2 h postdose (AUE0-2h) on drug liking and high visual analog scales.
  
  
  
  Thirty-three participants were randomized into treatment phase, and 29 completed all treatments. Study validity was confirmed with statistically significant differences in Emaxfor drug liking and high (p < 0.0001) between intravenous oxycodone and placebo. Intravenous simulated crushed ALO-02 resulted in significantly lower scores than oxycodone on drug liking (Emax: 58.2 vs. 92.4; AUE0-2h: 104.3 vs. 152.4) and high (Emax: 17.2 vs. 93.1; AUE0-2h: 12.0 vs. 133.6), respectively (p < 0.0001, all comparisons). More participants experienced adverse events after intravenous oxycodone (n = 27 [90%]) versus intravenous simulated crushed ALO-02 (n = 4 [12.5%]) or placebo (n = 2 [6.5%]).
  
  
  
  Intravenous administration of simulated crushed ALO-02 resulted in significantly lower abuse potential, as assessed by subjective ratings of drug liking and high, than intravenous oxycodone in nondependent, recreational opioid users. This suggests that injection of ALO-02 may not be as desirable to recreational opioid users compared with oxycodone taken for nonmedical reasons.
authors.affiliation: a PRA Health Sciences , Salt Lake City , UT , USA.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Backonja
authors.affiliation: a PRA Health Sciences , Salt Lake City , UT , USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
authors.affiliation: b Pfizer Inc , Durham , NC , USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Setnik
authors.affiliation: b Pfizer Inc , Durham , NC , USA.
authors.forename: Almasa
authors.initials: A
authors.lastname: Bass
authors.affiliation: b Pfizer Inc , Durham , NC , USA.|c Department of Medicine , Duke University Medical Center , Durham , NC , USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.affiliation: d Pfizer Inc, Collegeville , PA , USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Matschke
authors.affiliation: e Pfizer Inc , New York , NY , USA.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Malhotra
authors.affiliation: b Pfizer Inc , Durham , NC , USA.
authors.forename: Gernot
authors.initials: G
authors.lastname: Wolfram
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004192:Discrimination, Psychological / Q000187:drug effects; 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* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D010098:Oxycodone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D012054:Reinforcement, Psychology; D015819:Substance Abuse, Intravenous / Q000523:psychology*; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; C000608978:oxycodone naltrexone combination; D009271:Naltrexone; D010098:Oxycodone
keywords: Abuse potential; drug liking; intravenous; naltrexone; opioids; oxycodone