Efinaconazole Solution in the Treatment of Toenail Onychomycosis: A Phase 2, Multicenter, Randomized, Double-Blind Study

February 2013 | Volume 12 | Issue 2 | Original Article | 186 | Copyright © 2013

Eduardo H. Tschen MD,a Alicia D. Bucko DO,a Norihide Oizumi MS, Hideki Kawabata MS,Jason T. Olin PhD, and Radhakrishnan Pillai PhD

aAcademic Dermatology Associates, Albuquerque, NM bKaken Pharmaceutical Co Ltd, Kyoto, Japan cKaken Pharmaceutical Co Ltd, Tokyo, Japan dValeant Pharmaceuticals North America LLC, Bridgewater, NJ eDow

Abstract

Background: Onychomycosis is a common nail infection that is difficult to treat successfully. The prevalence increases with age and is associated with diabetes. Oral treatments are limited by drug interactions and potential hepatotoxicity; topical treatments, by modest efficacy.
Objective: We investigated the efficacy and safety of a solution using a novel topical triazole antifungal, efinaconazole, in distal lateral subungual onychomycosis (DLSO). Methods: Multicenter, randomized, double-blind, vehicle-controlled phase 2 study in mild to moderate toenail DLSO (n=135). Subjects randomized (2:2:2:1 ratio) to receive efinaconazole 10% solution (with or without semiocclusion), efinaconazole 5% solution, or vehicle, once daily for 36 weeks, with one 4-week posttreatment follow-up (week 40). Efficacy assessments included complete cure, mycologic cure, clinical efficacy, and other assessments of overall treatment effectiveness. No efficacy variables were designated as primary.
Results: At follow-up, complete cure was numerically higher in all active groups (16%-26%) compared with vehicle (9%). Mycologic cure rates with efinaconazole 10% semiocclusion, efinaconazole 10%, and efinaconazole 5% were 83%, 87%, and 87%, respectively. Efinaconazole 10% (with or without semiocclusion) demonstrated significantly greater clinical efficacy and treatment effectiveness when compared with vehicle (P=.0088 and .0064; .0056 and .0085, respectively, for both efinaconazole 10% groups). Adverse events were generally similar and mild. Local-site reactions were restricted to few subjects and did not differ meaningfully from those produced by vehicle.
Conclusions: This study provided evidence that once-daily efinaconazole 10% solution (with or without semiocclusion) applied topically for 36 weeks was more effective than vehicle in treating DLSO and was well tolerated. Based on these results, efinaconazole 10% solution was chosen for the phase 3 development program.

J Drugs Dermatol. 2013;12(2):186-192.

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INTRODUCTION

Onychomycosis is a progressive fungal infection of the nail bed, matrix, or plate that may lead to destruction and deformity of the toenails or fingernails.1,2 It is a common nail disorder, especially in older adults.1,3 Onychomycosis is associated with significant patient distress and major disability and pain, which may negatively affect a person’s well-being and self-esteem.4-7 Toenail onychomycosis frequently involves several nails8 and is particularly challenging to treat because of the slow nail growth and difficulties in delivering the drug to the site of infection in sufficient quantities to eradicate the pathogens.9,10

Currently, oral antifungal treatment has been generally required because of greater efficacy. Itraconazole and terbinafine, the only oral therapies approved by the US Food and Drug Administration (FDA), have reported complete cure rates of 14% and 38%, respectively.11,12 Yet their use may be limited in some patients by: (a) drug interactions, especially in elderly patients, where onychomycosis is most common and concomitant medications are frequently prescribed; (b) other safety concerns (eg, liver toxicity, neutropenia, and transient taste disturbance); and (c) the potential need for laboratory monitoring.13,14

A topical treatment for onychomycosis may be preferable to both physician and patient if it reduces the likelihood of systemic side effects and the requirement for laboratory monitoring. However, it would need to demonstrate comparable or complementary efficacy to oral therapy. Ciclopirox nail lacquer (the only topical product approved by the FDA) has demonstrated modest efficacy in onychomycosis, with reported complete cure rates from 5.5% to 8.5%,15 and requires frequent nail debridement. Difficulties in formulating a drug to penetrate through the nail plate and reach the infection in the nail bed in sufficient quantities to be effective have affected the development of topical treatments.16-18

This phase 2 study investigated the safety and efficacy of efinaconazole solution (IDP-108), a new topical triazole antifungal


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