upon definition of the disease state, treatment regimen, and treatment course. Due to the chronicity and possible co-presentation of onychomycosis, systemic therapy is often recommended for this disease state. Oral antifungals may not be accessible for all patients due to risk vs benefit when factoring in co-morbidities and drug–drug interactions. Considering
systemic therapy issues and the lack of data from large trials demonstrating safety and efficacy in the topical management of this clinical presentation, an unmet need has been created for a topical antifungal agent that can treat moccasin tinea pedis.
In a review of the literature, the first trial to investigate moccasin-type (along with interdigital tinea pedis) is the naftifine HCl gel 2% phase III clinical study. A member of the allylamine class, naftifine exhibits fungicidal, anti-inflammatory, and anti-bacterial properties.3-6 In vitro, naftifine exhibits fungicidal activity against the dermatophytes and many Candida species.
It stops fungal growth by inhibiting squalene epoxidase in the ergosterol synthesis pathway, which ultimately increases
cell membrane fragility and permeability. The mycological and clinical cure rates for naftifine in the treatment of tinea are superior or equivalent to those of terbinafine, econazole, and tolnaftate.7 In 2011, Parish et al showed that naftifine 2% cream (Naftin 2% cream, Merz) used once daily for two weeks in the management of interdigital tinea pedis had efficacy responses equivalent to naftifine 1% cream which was traditionally used for four weeks for the same infection.8 Naftifine 2% gel (Naftin
2% gel, Merz) was approved for the same dosing regimen as the 2% cream. The 2% gel was studied in a clinical trial that enrolled patients who had interdigital or both interdigital and moccasin-type tinea pedis.9
The overall study design was a two six-week, double-blind, randomized, vehicle-controlled, multi-center, parallel-group for this phase III clinical trial examining the safety and efficacy of naftifine HCl 2% gel for interdigital and moccasin tinea pedis. Subjects were placed into the interdigital-type only or the interdigital
with moccasin-type infection group. In order to focus on the moccasin-type only, a post-hoc analysis was completed to evaluate the safety and efficacy of a 2-week, once daily course of naftifine gel 2% versus vehicle for this sub-type.10
Over 40 sites were utilized in this study that enrolled male and female subjects aged 12–70 years old. A baseline clinical
presentation of moderate erythema, moderate scaling, mild pruritus, and positive KOH/mycology culture on one or both feet. Patients were not enrolled if they had uncontrolled diabetes,
plantar psoriasis, incapacitating tinea pedis, or atopic dermatitis.
As this is a fungal infection that is clinically symptomatic, investigators recorded two measurements to determine efficacy:
mycological analysis and clinical signs and symptoms. Mycological analysis was reported after two weeks of use and at week 6 (four weeks post-treatment). Clinical assessment measured the amount of erythema, scaling, and pruritus on a four-point scale (0=absent, 1=mild, 2=moderate, 3=marked) at those same time points. The primary efficacy endpoint of complete cure was defined as negative mycology (KOH/culture)
and a “0†score of erythema, scaling, and pruritus. In addition to complete cure, mycologic cure, treatment effectiveness,
clinical cure, and clinical success were also reported (Table 1). Safety assessments consisting of adverse events (AE’s), laboratory testing, and physical exam, were completed at defined visits.
A total of 1715 subjects were randomized, 1174 who had interdigital tinea pedis with or without moccasin-type and positive KOH and mycology culture at baseline were analyzed
for efficacy. Subjects included applied the study drug or vehicle once daily for two weeks to affected areas. The study subjects were then followed for four weeks after discontinuation
of the study drug. Those in the interdigital plus moccasin group applied the product both in the interspaces and the entire plantar foot. Of the 1174 subjects, 674 had interdigital tinea only while 500 had both moccasin and interdigital-type presentation. In the 500 moccasin/interdigital
group, only 380 subjects satisfied the inclusion criteria to qualify for data analysis. The 380 subjects comprise the post-hoc analysis.
