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Steady-State Pharmacokinetics of MNK-795, an Extended-Release Oxycodone and Acetaminophen Combination Analgesic: Results from 2 Active Comparator Studies

Krishna Devarakonda, Terri Morton, Michael Giuliani, Kenneth Kostenbader and Thomas Barrett

Two single-center, open-label, randomized, phase 1, multiple-dose studies (N=48 each) evaluated the steadystate pharmacokinetics and tolerability of MNK-795, a bilayer product with both immediate-release (IR) and extendedrelease (ER) components of oxycodone (OC) and acetaminophen (APAP; OC/APAP ER). Study 1 compared 1- and 2-tablet doses of OC/APAP ER (7.5 mg/325 mg; 15 mg/650 mg) administered every 12 hours and 1 tablet of IR OC/ APAP (7.5 mg/325 mg) administered every 6 hours over 4.5 days. Study 2 compared OC/APAP ER administered as 2 tablets (15 mg/650 mg) every 12 hours with IR oxycodone (15 mg), IR tramadol/APAP (37.5 mg/325 mg), and IR OC/APAP (7.5 mg/325 mg), each administered as 1 tablet every 6 hours over 4.5 days. In both studies, steady-state, dose-normalized, AUC0-12h, Cavg, and Cmin for oxycodone were similar between OC/APAP ER and each comparator; however, the degree of fluctuation and swing in oxycodone concentrations were greater with the more frequently dosed IR formulations. Acetaminophen concentrations reached similar peak levels to the IR products, but with OC/ APAP ER acetaminophen concentrations tapered to levels that were below those observed with the IR comparators by 7 hours after the last dose. The most commonly observed adverse events included nausea, vomiting, dizziness, and pruritus