Tavaborole 5% Topical Solution for the Treatment of Toenail Onychomycosis in Pediatric Patients: Results from a Phase 4 Open-Label Study
February 2019 | Volume 18 | Issue 2 | Original Article | 190 | Copyright © February 2019
Phoebe Rich MD,a Mary Spellman MD,b Vivek Purohit MPharm PhD,c Chuanbo Zang PhD,d and Tim J. Crook MD FFPME
aDermatology, Oregon Health and Science University and Oregon Dermatology and Research Center, Portland, OR bSan Francisco, CA cClinical Pharmacology, Pfizer Inc., Groton, CT dGlobal Biometrics & Data Management, Global Product Development, Pfizer Inc., Collegeville, PA EGlobal Product Development, Pfizer Inc., Tadworth, Surrey, UK
BACKGROUND: This study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of tavaborole in pediatric patients.
Study Design: In this open-label, single-arm study, pediatric patients (aged 6 to less than 17 years) with distal subungual onychomycosis affecting greater than equal to 20% of the target great toenail applied tavaborole once daily to all affected toenails (2 drops/great toenail, 1 drop/other toenail) for 48 weeks. In addition, a maximal-use subgroup (aged 12 to less than 17 years) applied tavaborole to all 10 toenails and less than equal to 2 mm of surrounding skin for the first 28 days.RESULTS: Treatment-emergent adverse events (TEAEs) were reported by 55.6% of patients; the most frequently reported (less than 5% of patients) were nasopharyngitis, contusion, sinusitis, and vomiting. Most TEAEs and local treatment reactions (LTRs) were mild or moderate and considered unrelated to treatment. There was 1 serious AE (severe appendicitis, considered unrelated to treatment) and there were no deaths, discontinuations because of AEs, or dose adjustments because of AEs. The most frequently reported LTRs were erythema and scaling. The incidence of LTRs diminished over time. Tavaborole was absorbed systemically, and plasma concentrations were measurable. The PK parameters determined in this study under maximal-use conditions indicate that steady state was achieved within the study period. For efficacy, 8.5% of patients achieved complete cure (clear nail and negative mycology [negative fungal culture and negative potassium hydroxide wet mount]) at week 52, and 14.9% achieved complete/almost complete cure at week 52 (clear or almost clear nail [less than equal to 5% dystrophic or discolored distal toenail plate] and negative mycology).CONCLUSION: Tavaborole was well tolerated in this pediatric population, and safety, PK, and efficacy profiles were comparable with those in adults.
Trial registration: ClinicalTrials.gov identifier: NCT03405818J Drugs Dermatol. 2019;18(2):190-195.
The estimated prevalence of onychomycosis among the adult population in Europe and North America is 4.3%.1 Although prevalence is lower among pediatric patients,2,3 the burden of disease with onychomycosis is still considerable, and pediatricians and parents are often hesitant to use long-term systemic antifungal treatments that necessitate laboratory monitoring or that are associated with significant adverse effects.4,5Tavaborole topical solution, 5%, (tavaborole) is a novel, boron-based, antifungal pharmaceutical agent approved by the US Food and Drug Administration for the treatment of adult toenail onychomycosis due to the dermatophytes Trichophyton rubrum or Trichophyton mentagrophytes.6 Because of the unique chemical properties of boron, small molecules that contain boron can form stable complexes with protein targets and inhibit enzyme activity, as in this case, with aminoacyl-transfer ribonucleic acid (tRNA) synthetase.7 In 2 phase 3 pivotal trials, tavaborole applied once daily for 48 weeks in adults with toenail onychomycosis had a statistically significant therapeutic effect, compared with vehicle, with favorable benefit:risk balance.8 This open-label study was designed to assess the safety and tolerability of tavaborole for the treatment of toenail onychomycosis in patients 6 to
The study was conducted in compliance with the Declaration of Helsinki and Good Clinical Practice. The clinical study protocol and amendments and the written informed consent form were reviewed and approved by IntegReview ethical review board (Austin, TX). Written informed consent was obtained for each patient before participation in any study-related activities.