A Phase 2, Controlled, Dose-Ranging Study of SB208, an Investigational Topical Nitric Oxide-Releasing Drug, for the Treatment of Tinea Pedis

August 2018 | Volume 17 | Issue 8 | Original Article | 888 | Copyright © 2018

Boni E. Elewski MD,a Leon H. Kircik MD,b Nathan Stasko PhD,c Emily De Leon MSCR,c Carolyn Enloe MPH,c Todd Durham PhD,c Tomoko Maeda-Chubachi MDc

aSchool of Medicine, University of Alabama, Birmingham, AL bIcahn School of Medicine at Mount Sinai Medical Center, New York City, NY cNovan, Inc., Morrisville, NC

Abstract

Background: Tinea pedis, or athlete’s foot, is a superficial, skin infection caused by dermatophytes. It is usually topically treated. Nitric oxide is endogenously produced in humans and has a variety of physiologic and antimicrobial properties. SB208 is a novel topical treatment comprising berdazimer sodium (a nitric oxide-storing macromolecule) and a hydrogel. Admixing these two components releases nitric oxide to the application site. Methods: A phase 2, double-blind, randomized trial evaluated the safety and efficacy of 3 doses of SB208 (2%, 4%, and 16%) vs matching vehicle, administered once daily for 14 days, in subjects with culture-confirmed interdigital tinea pedis. The primary efficacy outcome was the proportion of subjects with negative fungal cultures at end of treatment (day 14). Secondary outcomes at days 14 and 42 were the proportion of subjects with mycological cure (negative potassium hydroxide wet mount skin test and culture), clinical cure (reduced signs and symptoms from baseline graded on a 4-point scale). Safety was monitored through physical examinations, adverse events, and hemoglobin and methemoglobin levels. Efficacy outcomes were analyzed using a two-sided Cochran-Mantel-Haenszel test for general association, stratified by site. Results: At day 14, a higher proportion of patients had negative fungal cultures in the pooled SB208-treated group (62%; P=0.04) than the vehicle-treated group (43%). Of SB208 groups, the 4% group had higher incidence of negative fungal cultures vs the vehicle group (67.6% vs 42.9%; P=0.03). At day 42, pooled SB208-treated groups had significantly more mycological cure vs vehicle group (47% vs 31%, respectively; P=0.08), and clinical cure was maintained in 23% of pooled SB208-treated patients vs 14% of vehicle-treated patients. No safety concerns were reported. Adverse events were mild, not serious, and considered unrelated to study medications. Conclusions: Topical SB208 was effective and well tolerated in the treatment of tinea pedis. J Drugs Dermatol. 2018;17(8):888-893.

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INTRODUCTION

The incidence of mycologic diseases is rising, due to the increased use of communal recreational facilities, as well as the increased incidence of individuals who are immunocompromised.1 Tinea pedis, also known as athlete’s foot, is a common, superficial skin infection caused by dermatophytes. The worldwide prevalence of tinea pedis varies from 8% to 42%.2 The causative dermatophytes for tinea pedis are typically Trychophyton rubrum, Trychophyton mentagrophytes, and Epidermophyton floccosum. Tinea pedis manifests most often as an interdigital eruption, but may also present as a hyperkeratotic or vesiculobullous eruption. Frequently, tinea pedis is comorbid with tinea unguium (onychomycosis) and tinea cruris.Topical antifungal medications are first-line treatments for dermatomycoses,3 except in severe cases or in cases affecting the nail, ie, onychomycosis, when a systemic antifungal may be necessary. Topical antifungal agents used for superficial infections include allylamines (eg, terbinafine, naftifine) and azoles (including imidazoles, eg, luliconazole), hydroxypyridones (eg, ciclopirox olamine), thiocarbamates (eg, tolnaftate) and benzylamines (eg, butenafine). [El-Gohary 2014; Sahoo & Mahajan 2016] These treatments have highly variable rates of end-of-treatment and sustained mycologic cure.1,4 Therefore, more effective treatments with sustained efficacy are needed for tinea pedis.Nitric oxide is a free radical gas endogenously produced in humans essential in a variety of physiologic, pathologic, and homeostatic processes. It also has well described antimicrobial activities.5,6 Berdazimer sodium is an investigational, topical, nitric-oxide-containing agent with a novel mechanism of action. It has broad-spectrum antifungal activity and is unlikely to promote microbial resistance.7

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