Pharmacokinetic Bioequivalence Studies of an Extended-Release Oxycodone Hydrochloride Tablet in Healthy Japanese Subjects Under Fasting and Fed Conditions Without an Opioid Antagonist

Abstract

Oxycodone is a semisynthetic opioid used for the treatment of moderate to severe pain. Two separate studies were conducted to assess the pharmacokinetic bioequivalence of a newly formulated oxycodone hydrochloride extended-release tablet to a marketed oxycodone product in Japan under fasting and fed conditions. Each study was a randomized, open-label, single-dose, single-center, two-period, two-way crossover study. Healthy male Japanese subjects received the oxycodone 10-mg products under fasting and fed conditions. Blood samples were collected at specified time intervals, and plasma concentrations of oxycodone were analyzed using a validated liquid chromatography tandem mass spectrometry assay method. The pharmacokinetic parameters were determined via non-compartmental analysis. Pharmacokinetic metrics used for bioequivalence assessment were the maximum observed plasma concentration ( C _max) and the area under the concentration–time curve up to the last sampling time (AUC _t ). A total of 24 healthy subjects were enrolled in each study. One subject withdrew after completion of the first sequence under fed conditions. The ratios of geometric least square means for C _max and AUC _t under fasting conditions were 1.1110 (90% confidence interval [CI] 1.0562–1.1687) and 0.9946 (90% CI 0.9670–1.0231), respectively. The ratios of geometric least square means for C _max and AUC _t under fed conditions were 1.1417 (90% CI 1.0959–1.1895) and 1.0135 (90% CI 0.9810–1.0470), respectively. The 90% CIs were within the predefined range (0.80–1.25). Both treatments were well tolerated when taken without an opioid antagonist in healthy Japanese subjects. Pharmacokinetic bioequivalence between test and reference formulations under fasting and fed conditions was concluded in terms of both rate and extent of absorption.