Maribavir Is Bioequivalent in Fed and Fasted Healthy Subjects

Background: Maribavir (MBV) is an orally bioavailable antiviral drug with a novel mechanism of action against human cytomegalovirus (CMV) and a favorable tolerability profile. MBV is rapidly and well absorbed following oral administration with peak plasma concentrations generally achieved between 1.0 and 3.0 h post dose. In single-dose studies in healthy (50–1600 mg) and HIV-infected (100–1600 mg) subjects, the pharmacokinetics (PK) of MBV are approximately linear. This study was designed to determine the effect of co-administration of a moderately high-fat meal on the pharmacokinetics of MBV. Methods: This study was an open-label, randomized, crossover design performed at one investigational site. The study population included 15 men and 15 women and had a mean age of 29 years (range, 21–40 years). Eighteen subjects (60%) were black and 12 (40%) were white. Subjects received a single 400-mg dose of MBV administered as 2 × 200-mg tablets either after an overnight fast or within 5 minutes after completion of a standard, moderately high-fat breakfast. Treatments were separated by a 7- to 14-day washout interval. A full pharmacokinetic (PK) evaluation was performed over the 24 hours following each treatment. Standard safety monitoring was performed. Results: Oral MBV 400 mg was generally well tolerated when administered under either fasting or fed conditions. The most frequently reported treatment-emergent event was taste disturbance which occurred in 14/29 (48%) subjects. Mean (SD) PK parameters for MBV under fasting and fed conditions are shown below with results from ANOVA.Tabled 1FastingWith FoodRatio of Geometric Means (90%CI)Tmax(h)1.57 (0.68)2.47 (0.87)Different∗For Tmax, the p-value for testing for treatment effects was <0.0001 for MBV administered with food versus fasting conditions.Cmax(mcg/mL)16.7 (5.4)11.7 (2.4)0.722 (0.656, 0.793)AUC(0-t)(mcg∗h/mL)101 (36.4)86.3 (29.1)0.860 (0.802, 0.922)AUC(0-inf)(mcg∗h/mL)106 (42.0)91.5 (33.9)0.864 (0.804, 0.929)∗ For Tmax, the p-value for testing for treatment effects was <0.0001 for MBV administered with food versus fasting conditions. Open table in a new tab Time to MBV Cmax was delayed by administration after a high fat meal (Tmax 2.5 hours vs. 1.6 hours under fasting conditions). Although there is a decrease in AUC when MBV is administered with food, AUC values are considered equivalent as the 90% CIs are within the 0.80 to 1.25 range. Based on the ratio of geometric means of the two treatments, Cmax is 28% lower for MBV administered with food compared with fasting conditions (p<0.0001). Conclusions: A moderately high-fat meal was shown to have a modest effect on Cmax of MBV and to delay Tmax by about 1 hour but does not substantially alter the total exposure to MBV. These findings suggest that MBV can be taken without regard to food.