Background: Biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen\n(APAP) 7.5/325-mg tablets are formulated with gastroretentive ER drug delivery technology that has been\nassociated with clinically meaningful food effects in other approved products. Two phase 1 studies evaluated\npotential effects of food on single-dose pharmacokinetics of IR/ER HB/APAP tablets.\nMethods: These were single-center, open-label, randomized, single-dose, 3-period crossover studies in healthy\nvolunteers (aged 18ââ?¬â??55 years). IR/ER HB/APAP was administered as a single 2-tablet dose (study 1) or 3-tablet dose\n(study 2) under fed (high- and low-fat) and fasted conditions. Area under the plasma concentration-time curve\nfrom 0 h to time t (AUC0ââ?¬â??t) and from time 0 extrapolated to infinity (AUC0ââ?¬â??inf) and maximum observed plasma\nconcentration (Cmax) of hydrocodone and APAP under fed versus fasted conditions were compared using analysis\nof variance. A 90 % confidence interval of the geometric least squares mean ratio fully contained within 80 to\n125 % indicated no treatment difference. Safety and tolerability were assessed.\nResults: Forty of 48 participants in study 1 and 21 of 30 in study 2 completed all treatments. In both studies, under\nfed (high- or low-fat meal) versus fasted conditions, 90 % CIs for AUC0ââ?¬â??t and AUC0ââ?¬â??inf for both hydrocodone and\nAPAP were entirely contained within the bioequivalent range (80ââ?¬â??125 %), indicating that high- and low-fat meals\ndid not affect the extent of exposure. In both studies, a high-fat meal did not affect the Cmax for hydrocodone.\nHydrocodone Cmax was not affected by a low-fat meal in study 1 but increased by approximately 19 % in study 2.\nA high-fat meal decreased APAP Cmax by approximately 20 % (study 1) and 13 % (study 2); a low-fat meal\ndecreased APAP Cmax by 22 % (study 1) and 21 % (study 2). Approximately 50 % of participants in both studies\nreported ââ?°Â¥1 treatment-emergent adverse event (TEAE), with no notable difference based on food intake. There\nwere no serious or severe AEs. The most common TEAEs were nausea, vomiting, and dizziness.\n(Continued on next page) (Continued from previous page)\nConclusions: Pharmacokinetic and safety findings were similar regardless of food intake. TEAEs were consistent\nwith those reported with low-dose combination opioids. IR/ER HB/APAP can be administered without regard\nto food.
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