• Beatrice Setnik, Kerri Schoedel, Cindy Bartlett, Chris Dick, Nasrat Hakim, and Pierre Geoffroy.
• VP Clinical Pharmacology, INC Research, Inc, Raleigh, North Carolina.
• J Opioid Manag. 2017 Nov 1; 13 (6): 449-464.

ObjectiveTo assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone.DesignRandomized, double-blind, double-dummy, active and placebo-controlled, five-way crossover study. Pharmacodynamics, safety, and pharmacokinetics (PKs) were evaluated for up to 36 hours postdose.SettingSingle site in Canada (INC Research Toronto).ParticipantsHealthy male and female nondependent recreational opioid users underwent a naloxone challenge and drug discrimination qualification test.InterventionSingle IN dose of ground ELI-200 (30-mg oxycodone hydrochloride [HCl]/3-mg naltrexone HCl), crushed 30-mg oxycodone HCl IR (Roxicodone®), placebo, fixed placebo, and single oral dose of intact ELI-200 (30mg/3mg).Main Outcome MeasurePeak effect (Emax) for bipolar Drug Liking (0-100 point visual analog scale).ResultsOf the 44 randomized subjects, 37 completed all five treatment periods. All active treatments showed significantly higher (p<0.001) median Drug Liking Emax relative to placebo. Significant reductions (p<0.001) in median Drug Liking [Emax] were observed for IN ELI-200 [56.0] compared to IN oxycodone IR [100.0]. Secondary positive or objective measures (High, Good Drug Effects, Overall Drug Liking, Take Drug Again, and maximum pupil constriction) showed significantly lower Emax for IN ELI-200 (p<0.001) compared to IN oxycodone IR.ConclusionsIN administration of ELI-200 demonstrated significantly decreased effects on subjective and physiologic measures, and greater nasal irritation, compared to IN oxycodone IR. These findings, along with the PK profile of naltrexone, demonstrated that when ELI-200 capsules were ground and administered intranasally, the naltrexone component was rapidly released and conferred meaningful abuse-deterrent properties.

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