Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational opioid users

ABSTRACT

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 (E_max) and area under the effects curve within 2 h postdose (AUE_0-2h) 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 E_max 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 (E_max: 58.2 vs. 92.4; AUE_0-2h: 104.3 vs. 152.4) and high (E_max: 17.2 vs. 93.1; AUE_0-2h: 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.

KEYWORDS:

• Abuse potential
• intravenous
• drug liking
• opioids
• oxycodone
• naltrexone

Supplemental

Supplemental data for this article can be accessed on the publisher’s website.

Funding

This study was sponsored by Pfizer. Medical writing support was provided by Vardit Dror, PhD, and Diane Hoffman, PhD, of Engage Scientific Solutions and was funded by Pfizer.

Declaration of interest

Bass A, Matschke K, Malhotra BK, and Wolfram G are full-time employees of Pfizer and hold stock options and/or shares. Setnik B and Sommerville KW were Pfizer employees when the study was conducted and held stock options at that time. Setnik B is currently affiliated with INC Research, Raleigh, NC. Sommerville KW is currently affiliated with GW Pharmaceuticals, Durham, NC. Webster L is a full-time employee of PRA Health Sciences (formerly CRI/Lifetree) and discloses honoraria and travel expenses for consultation and advisory board participation for the following companies: AstraZeneca, Cara Therapeutics, CVS Caremark, Charleston Labs, Collegium Pharmaceuticals, Inspirion Pharmaceuticals, Insys Therapeutics, Kaleo, Mallinckrodt Pharmaceuticals, Marathon Pharmaceuticals, Merck, Orexo Pharmaceuticals, Pfizer, Proove Biosciences, Signature Therapeutics, Teva, Trevena, and Zogenix. Backonja M is a full-time employee of PRA Health Sciences.

Additional information

Funding

This study was sponsored by Pfizer. Medical writing support was provided by Vardit Dror, PhD, and Diane Hoffman, PhD, of Engage Scientific Solutions and was funded by Pfizer.