subjects and 5 of the 6 adult subjects (resulting from missing data) were analyzed for PK. Efficacy data was available for all 22 pediatric
subjects. All 28 subjects dosed were analyzed for safety.
Among pediatric subjects enrolled, the majority were male (82%), Black or African American (73%), and with a mean (SD) age of 14.7 (1.7) years. For the adult subjects, the majority were male (67%), most were Black or African American (50%) or White (33%) and had a mean (SD) age was 31.7 (11.2) years (Table 1).
Pharmacokinetics – Plasma
Exposure to naftifine increased over the 2-week treatment period
with the use of naftifine hydrochloride gel 2%: for pediatric subjects, geometric mean AUC0-24 (CV%) was 15890.1 pg*h/mL (211.6%) on day 1 and AUCΤ,ss was 60038.5 pg*h/mL (131.1%) on day 14; for adult control subjects, geometric mean AUC0-24 was 17213.9 pg*h/mL (88.1%) on day 1 and AUCΤ,ss was 72849.8 pg*h/mL (71.1%) on day 14. Maximum plasma concentration also increased over the treatment period for both the pediatric
and adult subjects. In pediatric subjects, the median time
to maximum plasma concentration (tmax) was 23.8 hours with a range of 1-24 hours after single application on day 1 and 23.8 hours with a range of 4-24 hours on day 14. In the adult control subjects, the median tmax (range) was 12.0 hours (8-24 hours) after a single application on day 1 and 5.0 hours (4-6 hours) on day 14 (Table 2).
After naftifine hydrochloride gel 2% maximal use administration (2 grams on each foot), plasma concentrations of naftifine from day 1 (single dose) through day 14 (multiple dose, steady state) in pediatric subjects were similar to those observed in adult subjects. The median time to maximum trough concentration (ttrough,max) of naftifine was twice as long in pediatric subjects (14.0 days, range, 2-21 days; all subjects had ttrough,max between 2 and 15, inclusive, with the exception of one subject for whom there may have been a sample error on day 21) compared with adult subjects (7.0 days, range: 2-13 days; Table 2). Additionally, the geometric mean of maximum naftifine concentration at trough (Ctrough,max) for pediatric and adult control subjects is presented in Table 2. Day 14 plasma concentrations were higher and less variable than day 1 plasma concentrations in both pediatric and adult control subjects. Naftifine continued to be detected in the plasma in most subjects at day 28, when the geometric mean (CV%) was 347.382 pg/mL (80.6%) in the pediatric group and 563.135 pg/mL (91.3%) in the adult control group.
Pharmacokinetics – Urine
In pediatric subjects, mean Ae0-24 (range) increased from 380.9 ng (0-1135.4 ng) on day 1 to 823.0 ng (0-2202.3 ng) on day 14;
