The Efficacy and Safety of Efinaconazole 10% Solution for Treatment of Mild to Moderate Onychomycosis: A Pooled Analysis of Two Phase 3 Randomized Trials
July 2014 | Volume 13 | Issue 7 | Original Article | 815 | Copyright © July 2014
Aditya K. Gupta MD PhD FRCPC,a,b Boni E. Elewski MD,c Jeffrey L. Sugarman MD PhD,d
Chikara Ieda,e Hideki Kawabata MS,e Robert Kang PhD,f Radhakrishnan Pillai PhD,g
Jason T. Olin PhD,f and Shinichi Watanabe MD PhDh
aDepartment of Medicine, University of Toronto, Toronto, Canada
bMediprobe Research Inc. London, Canada
cDepartment of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL
dDepartment of Dermatology, University of California, San Francisco, CA
eKaken Pharmaceutical Co Ltd, Tokyo, Japan
fValeant Pharmaceuticals North America LLC, Bridgewater, NJ
gDow Pharmaceutical Sciences Inc., Petaluma, CA
hDepartment of Dermatology, Teikyo University School of Medicine, Tokyo, Japan
Abstract
BACKGROUND: Onychomycosis is a fungal infection of the nail apparatus that can be challenging to treat due to the modest efficacy of
existing antifungal therapies and a high rate of relapse and recurrence.
OBJECTIVES: To investigate the efficacy and safety of efinaconazole 10% solution in pooled Phase III clinical trial participants with mild
to moderate onychomycosis.
METHODS: Phase III clinical trials data from NCT01008033 and NCT01007708 were pooled. Efficacy analysis for the primary and secondary
outcome variables was conducted using the mITT population and analysed using Cochran-Mantel-Haenszel tests. Subgroup analysis
was conducted for prognostic factors that may affect drug efficacy. Safety analysis was conducted on all recipients of a single drug dose.
RESULTS: Efinaconazole 10% nail solution was superior to vehicle for all primary and secondary outcome measures assessed. Complete
cure was 18.5% vs 4.7%
P<0.001 [mITT] and mycological cure was 56.3% vs 16.6%,
P<0.001 [mITT]. Complete or almost complete
cure and treatment success were achieved in 27.7% and 47.2% compared to 7.9% and 18.2% with vehicle, respectively (
P<0.001
[mITT]). In all subgroups, efinaconazole 10% solution had statistically higher cures rates compared to vehicle. Higher complete cure
rates were observed in women and individuals with mild disease (≤33% involvement), but not in any other subgroup assessed. Treatment
associated adverse events in the efinaconazole 10% solution group were similar to vehicle and limited to local site reactions (2%).
CONCLUSIONS: The findings from this pooled analysis suggest that efinaconazole 10% solution may become the preferred topical agent
for mild to moderate onychomycosis.
J Drugs Dermatol. 2014;13(7):815-820.
INTRODUCTION
Efinaconazole 10% solution is an antifungal drug that recently
completed parallel Phase III clinical trials for the
treatment of distal and lateral subungual onychomycosis
(DLSO).1 Efinaconazole is a triazole derivative that inhibits ergosterol
biosynthesis with a high in vitro efficacy.2,3 It has been
formulated in a topical solution specifically designed for the
treatment of onychomycosis. The initial report on the parallel
Phase III trials confirmed that efinaconazole 10% solution is an
effective and safe option for the topical treatment of DLSO.1 It
received Health Canada approval on October 2, 2013.
Efinaconazole 10% solution was formulated to address the challenges
of treating onychomycosis. The current oral therapies
have moderate efficacy,4–6 but they are associated with systemic
adverse events and drug interactions.7–9 Onychomycosis has an
increased prevalence in males,10 the elderly,11 diabetics,12 individuals
with poor peripheral perfusion,13 and immunocompromised
patients.14 These patients often undergo polypharmacy, putting
them at increased risk for adverse events, which excludes a subset
of the population who are the most vulnerable to complications
like diabetic foot syndrome and systemic infections.15–17 Topical
therapy may be preferred, as it decreases the systemic exposure
of the drug; however, current topical options have not proven as
effective as oral drugs due to issues of penetrance through the
nail plate.18 The formulation of efinaconazole 10% solution was developed
specifically to increase uptake of the drug.
