The Efficacy and Safety of Tavaborole, a Novel, Boron-Based Pharmaceutical Agent: Phase 2 Studies Conducted for the Topical Treatment of Toenail Onychomycosis

September 2014 | Volume 13 | Issue 9 | Original Article | 1124 | Copyright © 2014

Mirna E. Toledo-Bahena MD,a Alicia Bucko DO JD,b Jorge Ocampo-Candiani MD,c Maira E. Herz-Ruelas MD,c
Terry M. Jones MD,d Michael T. Jarratt MD,e Richard A. Pollak DPM MS,f Lee T. Zane MDg

aInstituto Mexicano de Investigación Clínica, Roma Norte, Cuauhtémoc, Distrito Federal, Mexico
bAcademic Dermatology Associates, Albuquerque, NM
cDepartment of Dermatology, University Hospital José Eleuterio González, Universidad Autónoma de Nuevo León (UANL), Monterrey,
NL, Mexico
dJ&S Studies, Inc., College Station, TX
eDermResearch, Inc., Austin, TX
fEndeavor Clinical Trials, San Antonio, TX
gAnacor Pharmaceuticals, Inc., Palo Alto, CA

Abstract

OBJECTIVE: To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes.
METHODS: One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.5%, 5.0%, or 7.5%. Patient cohort 3 of study 2 received open-label tavaborole 5.0% once daily for 360 days. All three studies assessed day 180 treatment success, defined as complete or partial clinical evidence of clear nail growth plus negative fungal culture.
RESULTS: A total of 336 patients were included in the intent-to-treat (ITT) or modified ITT populations and efficacy analyses across the 3 studies. In study 1, treatment success rates at day 180 were higher with tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (27%, 26%, and 32% vs 14%, respectively; slope P=0.030). In cohort 3 of study 2, 7% of patients achieved treatment success with tavaborole 5.0% at day 360. Negative culture rates at day 180 in study 1 were numerically higher for tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (slope P=0.046). Application-site reactions of general irritation, erythema, scaling, and stinging/burning were most common with tavaborole 7.5%, were generally mild to moderate, and resolved with treatment discontinuation and/or a reduction in dosing frequency. No systemic safety concerns were observed.
CONCLUSION: Tavaborole solution demonstrated favorable efficacy and safety in phase 2 clinical studies. Based on these findings, tavaborole topical solution, 5% was further investigated in larger, more definitive phase 3 studies. Results from these completed phase 3 studies will provide additional evidence regarding the safety and efficacy of tavaborole in the treatment of toenail onychomycosis.

J Drugs Dermatol. 2014;13(9):1124-1132.

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INTRODUCTION

Onychomycosis is a fungal infection of the nail unit caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes in greater than 90% of cases,1 and most often affects the toenails.2 This fungal infection affects between 3% to 18% of adults, with prevalence increasing with age,1,2 and is marked clinically by the presence of white/yellow or orange/brown patches or streaks in or beneath the nail plate, subungual hyperkeratosis and debris, and nail plate thickening. If untreated, the infection often progresses and may lead to discomfort and pain; in patients with comorbid conditions such as diabetes, human immunodeficiency virus (HIV), vascular disease, or renal disease, there is heightened risk of secondary complications including skin ulceration and systemic infection.3 Recurrence of onychomycosis is common, and may be related to environmental, occupational, and genetic factors, or certain clinical features of the initial infection.4-6

Current treatment options for distal subungual onychomycosis include oral agents, topical treatments, a combination of systemic and topical therapies, and laser procedures. Terbinafine and itraconazole are oral antifungal agents approved by the United States Food and Drug Administration (US FDA) for the treatment of onychomycosis7,8; terbinafine is the most frequently prescribed oral antifungal for onychomycosis in the US and Canada. Although fluconazole and posaconazole are not approved for the treatment of onychomycosis by the

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