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Intranasal abuse potential of an abuse-deterrent oxycodone formulation compared to oxycodone immediate release and placebo in nondependent, recreational opioid users

Beatrice Setnik, PhD, Kerri Schoedel, PhD, Cindy Bartlett, MMath, Chris Dick, MS, MBA, Nasrat Hakim, MS, LLM, Pierre Geoffroy, MDCM, MSc, FCFP, DABAM

Abstract


Objective: To assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone.

Design: Randomized, 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.

Setting: Single site in Canada (INC Research Toronto).

Participants: Healthy male and female nondependent recreational opioid users underwent a naloxone challenge and drug discrimination qualification test.

Intervention: Single 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 (30 mg/3 mg).

Main Outcome Measure: Peak effect (E max) for bipolar Drug Liking (0-100 point visual analog scale).

Results: Of the 44 randomized subjects, 37 completed all five treatment periods. All active treatments showed significantly higher (p < 0.001) median Drug Liking E max relative to placebo. Significant reductions (p < 0.001) in median Drug Liking [E max ] 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 E max for IN ELI-200 (p < 0.001) compared to IN oxycodone IR.

Conclusions: IN 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.


Keywords


abuse-deterrent formulations, abuse liability, oxycodone, opioid abuse, opioid antagonist

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References


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DOI: http://dx.doi.org/10.5055/jom.2017.0421

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