生物学的同等性とバイオアベイラビリティのジャーナル

概要

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

Bimal Malhotra, Kyle Matschke, Candace Bramson, Qiang Wang and Joanne Salageanu

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.