An Open-Label, Multi-Center, Multiple-Application Pharmacokinetic Study of Naftifine HCl Gel 2% in Pediatric Subjects With Tinea Pedis

the plasma concentration curve within the first 24 hours; 2) C_max: the highest observed concentration following a single dose administration; 3) AUC_{Τ, ss}: area under the plasma concentration curve within a dosing interval at steady state; 4) C_{max, ss}: maximum observed plasma concentration at steady state; 5) t_max: time to concentration maximum after single dose; 6) t_{max, ss:} time to concentration maximum at steady state; 7) C_trough: trough plasma concentration; 8) t_trough,max: time to maximal trough plasma concentration; 9) C_{trough, max}: maximum observed trough plasma concentration; 10) Ae_0-24: partial amount of unchanged drug excreted into urine within the first 24 hours after single dose; 11) f_e: fraction of administered drug excreted into the urine after a single dose and during a dosing interval at steady state; 12) CL_R: renal clearance after single dose and multiple doses; 13) Ae_{Τ, ss}: amount of unchanged drug excreted into urine during a dosing interval at steady state.

Efficacy measurements included mycology laboratory analysis for the presence of dermatophytes (KOH scraping assessment and fungal culture) and scoring of clinical signs and symptoms (erythema, scaling, and pruritus) severity on a four point scale (0=absent, 1=mild, 2=moderate, 3=marked).

The following efficacy outcomes are based on clinical and mycology data evaluated: complete cure (negative mycology results [KOH and culture] and complete absence [score of 0 for each] of erythema, scaling, and pruritus); mycological (negative KOH and culture results); treatment effectiveness (mycological cure and erythema, scaling, and pruritus scores of 0 or 1); clinical cure (erythema, scaling, and pruritus scores of 0); and clinical success (erythema, scaling, and pruritus scores of 0 or 1). All of the aforementioned endpoint evaluations were performed at day 7 (1-week into treatment), day 14 (end of treatment), and day 28 (2-weeks post-treatment).

Safety assessments included adverse events (AEs), clinical laboratory values, and physical examination findings.

This study was not intended to be confirmatory in nature. Therefore, the sample size is not based on statistical power calculations. It was planned to screen 35 subjects in order to have 28 subjects enrolled to obtain 22 PK evaluable subjects for treatment with naftifine hydrochloride gel 2%. This sample size was determined to be sufficient to address the PK objectives of the study and to be able to detect differences in pharmacokinetics between the pediatric and adult control subjects if they are existent without exposing too large of a number of subjects to undue risk and discomfort. As a result, the planned distribution of subjects needed for a robust pharmacokinetic analysis was 18 PK evaluable pediatric subjects and 4 PK evaluable adult control subjects. The adult cohort is smaller than the pediatric cohort because they served as controls and PK data of adults is already available from former naftifine studies (Data on file, Merz Pharmaceuticals, LLC).

The time courses of the plasma and urine concentrations of naftifine hydrochloride gel 2% was analyzed by non-compartmental analysis. PK variables was described by statistical characteristics (number of observations, arithmetic mean, standard deviation (SD), arithmetic coefficient of variation, geometric mean, and geometric coefficient of variation, median, minimum and maximum) per treatment group and per age group (pediatric and adult).

All efficacy endpoints were described by statistical characteristics for categorical data (n [%]). In addition, a two-sided 90% CI for percentages was computed using the exact method.

Incidences of adverse events during the study period were tabulated and summarized descriptively for both treatment groups. Incidences were calculated for treatment emergent adverse events (TEAEs) on the system organ class level and on the preferred term level and presented by treatment (ie, total and in percent, by intensity and by relationship). Adverse events were also summarized by age cohort.

A total of 28 subjects were enrolled and treated (22 pediatric and 6 adult subjects). Twenty-one of the 22 pediatric subjects and 4 of the 6 adult subjects completed the study; however, all 22 pediatric