Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials

BACKGROUND: Biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) 7.5/325-mg tablets are formulated with gastroretentive ER drug delivery technology that has been associated with clinically meaningful food effects in other approved products. Two phase 1 studies evaluated potential effects of food on single-dose pharmacokinetics of IR/ER HB/APAP tablets. METHODS: These were single-center, open-label, randomized, single-dose, 3-period crossover studies in healthy volunteers (aged 18–55 years). IR/ER HB/APAP was administered as a single 2-tablet dose (study 1) or 3-tablet dose (study 2) under fed (high- and low-fat) and fasted conditions. Area under the plasma concentration-time curve from 0 h to time t (AUC(0–t)) and from time 0 extrapolated to infinity (AUC(0–inf)) and maximum observed plasma concentration (C(max)) of hydrocodone and APAP under fed versus fasted conditions were compared using analysis of variance. A 90 % confidence interval of the geometric least squares mean ratio fully contained within 80 to 125 % indicated no treatment difference. Safety and tolerability were assessed. RESULTS: Forty of 48 participants in study 1 and 21 of 30 in study 2 completed all treatments. In both studies, under fed (high- or low-fat meal) versus fasted conditions, 90 % CIs for AUC(0–t) and AUC(0–inf) for both hydrocodone and APAP were entirely contained within the bioequivalent range (80–125 %), indicating that high- and low-fat meals did not affect the extent of exposure. In both studies, a high-fat meal did not affect the C(max) for hydrocodone. Hydrocodone C(max) was not affected by a low-fat meal in study 1 but increased by approximately 19 % in study 2. A high-fat meal decreased APAP C(max) by approximately 20 % (study 1) and 13 % (study 2); a low-fat meal decreased APAP C(max) by 22 % (study 1) and 21 % (study 2). Approximately 50 % of participants in both studies reported ≥1 treatment-emergent adverse event (TEAE), with no notable difference based on food intake. There were no serious or severe AEs. The most common TEAEs were nausea, vomiting, and dizziness. CONCLUSIONS: Pharmacokinetic and safety findings were similar regardless of food intake. TEAEs were consistent with those reported with low-dose combination opioids. IR/ER HB/APAP can be administered without regard to food. TRIAL REGISTRATION: ClinicalTrials.gov NCT02561650 and NCT02561741. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-015-0032-y) contains supplementary material, which is available to authorized users.