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

July 2015 | Volume 14 | Issue 7 | Original Article | 686 | Copyright © July 2015

Amit Verma DrPH MPH, Babajide Olayinka MSc, Alan B. Fleischer Jr. MD

Merz North America, Inc., Raleigh, NC

Abstract
BACKGROUND: Tinea pedis is the most common superficial fungal infection. Naftifine hydrochloride is a topical antifungal of the allylamine class, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects. Clinical data on topical antifungal therapy using naftifine for tinea pedis in a pediatric population is limited.
OBJECTIVE: To assess trends in efficacy, tolerability, safety, and to quantify the pharmacokinetics (PK) of topical naftifine hydrochloride gel 2% in pediatric subjects with tinea pedis.
METHODS: Twenty-eight subjects (22 pediatric and 6 adult controls) were enrolled and treated in the study. Approximately 2 grams of naftifine hydrochloride gel 2% was applied to each foot (4 grams total) for subjects with tinea pedis. Pharmacokinetic blood and urine samples were collected at various time points throughout the study. Efficacy was assessed based on potassium hydroxide, dermatophyte culture, and signs and symptom results at days 7, 14, and 28. Adverse event information was collected routinely.
RESULTS: The rate and extent of systemic exposure among the pediatric and adult control subjects was low. Adverse events were minimal and were not related to treatment. Positive results were observed as early as day 7; however the proportion of subjects achieving success generally increased over time through day 28 in both treatment groups.
CONCLUSIONS: Naftifine hydrochloride gel 2% was found to be well tolerated and safe. Trends in clinical benefit were observed throughout the treatment period; however, continued improvement in efficacy rates were observed during the post-treatment period.

J Drugs Dermatol. 2015;14(7):686-691.

INTRODUCTION

Fungal infections caused by dermatophytes, yeasts, and molds occur globally, affecting millions of people. Although the infection can result from contact with an infected animal, soil, or fomites, most infections are caused by dermatophytes spread through contact with an infected person, or by self-infection by transfer from another body part.1, 2 A fungal infection involving the foot, referred to as tinea pedis, affects up to 15% of the United States population and is estimated to be the second most common skin condition, behind acne. Additionally, approximately half of those infected suffer from reoccurring outbreaks.2-5 Tinea pedis is more common in adolescents and adult males; however, women and children may come into contact with an infected person or surrounding environments of a contagious nature.6, 7
The three main types of dermatophytes isolated as the primary cause of tinea pedis are Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. 5 Trichophyton rubrum accounts for approximately three-fourths of all superficial fungal diseases in a representative sample of the US population.2, 5 Specifically to tinea pedis, Trichophyton rubrum accounts for two-thirds of the cases of tinea pedis.2, 5
Both topical and oral regimens are prescribed for the treatment of tinea infections. Generally, a topical application of an antifungal agent is the most common recommendation by a healthcare provider for the treatment of tinea pedis; however, in some cases oral treatments are warranted.8 Although oral regimens are an option for treatment, due to the increased risk of undesirable systemic affects, topical treatments tend to be an effective alternative. A commonly prescribed topical treatment for tinea pedis is a two-week once daily application of naftifine hydrochloride gel 2%.
Naftifine hydrochloride is a broad-spectrum antifungal agent of the allylamine class and has been shown to demonstrate better efficacy rates and shorter treatment durations than the azole class.9-11 Additionally, naftifine hydrochloride has been shown to demonstrate potent fungicidal and fungistatic activity as well as clinically significant anti-inflammatory and anti-bacterial effects.12-16 In clinical trials, naftifine hydrochloride gel 2% has been shown to be efficacious and in most cases post-treatment improvements have been observed up to four weeks after treatment cessation.17-19 One possible explanation for this continued post-treatment improvement is bioavailable drug remaining in the deeper layers of the