Relative Bioavailability Study of an Abuse-Deterrent Formulation of Extended-Release Oxycodone with Sequestered Naltrexone (ALO-02) Versus Immediate-Release Oxycodone Tablets in Healthy Volunteers
- *Corresponding Author:
- Bimal K Malhotra
Sr. Director, Clinical Pharmacology, Pfizer Inc
235 East 42nd Street, New York, NY 10017, USA
E-mail: [email protected]
Received Date: August 12, 2014; Accepted Date: October 07, 2014; Published Date: November 01, 2014
Citation: Malhotra B, Matschke K, Bramson C, Wang Q, Salageanu J (2014) Relative Bioavailability Study of an Abuse-Deterrent Formulation of Extended-Release Oxycodone with Sequestered Naltrexone (ALO-02) Versus Immediate-Release Oxycodone Tablets in Healthy Volunteers. J Bioequiv Availab 6: 186-191. doi: 10.4172/jbb.1000202
Copyright: © 2014 Malhotra B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: ALO-02, an opioid formulation intended to deter abuse, comprising capsules filled with pellets of extended-release oxycodone hydrochloride, an opioid, surrounding sequestered naltrexone hydrochloride, an opioid antagonist. This study compared oxycodone pharmacokinetics following ALO-02 (oxycodone/naltrexone 40 mg/4.8 mg) versus immediate-release oxycodone (IRO) tablets (20 mg). Methods: This was an institutional review board–approved, open-label, single-dose, randomized, two-way crossover study in 14 healthy fasted adults (aged 18 to 55 years). Plasma concentrations of oxycodone, naltrexone, and 6-β-naltrexol were determined. Maximum plasma concentration (Cmax), area under the plasma concentrationtime profile from time 0 to infinity (AUCinf) and to the last quantifiable concentration (AUClast), time to Cmax (Tmax), and terminal half-life (t1/2) were determined. Adverse events (AEs) were recorded throughout the study. Results: Median oxycodone Tmax was prolonged (12 versus 1 hours) and mean t1/2 was longer (7.2 versus 4.6 hours) for ALO-02 versus IRO. ALO-02/IRO ratio (90% confidence interval [CI]) of adjusted geometric means for dose-normalized AUCinf was 107.2% (96.7%, 118.8%), with CI contained within equivalence limits of 80%–125%. Dose-normalized ALO-02/IRO Cmax ratio (90% CI) was 33.0% (28.8%, 37.9%). Following ALO-02 administration, plasma naltrexone concentrations were below the limit of quantification (BLQ; 4.00 pg/mL), and 6-β-naltrexol concentrations were BLQ (4.00 pg/mL) in >50% of participants or generally low (<50.0 pg/mL). Most AEs were mild, with nausea and dizziness being most frequent. Conclusion: Pharmacokinetic comparisons indicate equivalent oxycodone bioavailability under fasted conditions. The lower Cmax and longer Tmax and t1/2 observed for ALO-02 versus IRO are consistent with the extended-release profile of ALO-02 formulation. Low naltrexone and 6-β-naltrexol concentrations indicated successful sequestration of naltrexone in ALO-02.