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Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational
Miroslav Backonja1, Lynn R Webster1, Beatrice Setnik2
1a PRA Health Sciences , Salt Lake City , UT , USA.
Background:
ALO-02, comprising pellets of extended-release oxycodone surrounding sequestered naltrexone, is intended to deter abuse.
Objective:
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.
Methods:
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.
Results:
Thirty-three participants were randomized into treatment phase, and 29 completed all treatments. Study validity was confirmed with statistically significant differences in Emax for 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%]).
Conclusion:
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.