Single- and multiple-dose study to evaluate pharmacokinetics, safety and tolerability in healthy volunteers: A comparison of extended-release oxycodone with sequestered naltrexone 40mg twice daily to oxycontin 40mg twice daily and extended-release oxycodone with sequestered naltrexone 80mg once daily

摘要

ALO-02 capsules (ALO-02) contain pellets that consist of extended-release oxycodone that surrounds sequestered naltrexone. The primary objective was to characterize the pharmacokinetics (PK) of oxycodone following single- and multiple-dose oral administration of ALO-02 40mg BID in healthy volunteers. Secondary objectives were to characterize (1) the PK of oxycodone following single- and multiple-dose administration of a comparator OxyContin (OXY-ER) 40mg BID as well as an alternate regimen of ALO-02 80mg QD, and (2) the safety and tolerability assessments. Healthy volunteers received three treatments on a background of oral naltrexone (50mg). Noncompartmental PK parameters were calculated for oxycodone. All 12 subjects were male with a mean age (SD, range) of 44.6 years (7.6, 25-55). Single-dose PK results for ALO-02 indicate that median peak plasma oxycodone concentrations were reached by 12hours compared to 4hours for OXY-ER. Compared to OXY-ER, mean dose-normalized, single-dose Cmax values were approximately 27% and 23% lower for ALO-02 40mg BID and ALO-02 80mg QD treatments, respectively. Following multiple doses all treatments reached steady state by 3 days. At steady state, oxycodone peak-to-trough fluctuation was significantly lower for ALO-02 BID versus OXY-ER. Adverse events were consistent with opioid therapy. ALO-02 40mg BID treatment provided a PK profile appropriate for around-the-clock treatment of chronic pain.