Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double‐blind, randomized phase III study

Abstract

Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.

Efficacy and safety of fosravuconazole L‐lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double‐blind, randomized phase III study

“…Nevertheless, a complete cure rate of 59.4% at week 48 was obtained. Although the above studies were conducted under different protocols, such that simple comparisons are not feasible, the results of our current study suggest higher efficacy of F‐RVCZ for onychomycosis as compared with the complete cure rates achieved in previous clinical studies of drugs for onychomycosis . The subgroup analysis results according to age (<65 or ≥65 years), sex, fungal species and nail involvement ratio at screening (<50% or ≥50%) demonstrated significantly higher efficacy of F‐RVCZ than placebo in all subgroups, suggesting substantial efficacy of F‐RVCZ regardless of baseline patient characteristics.…”

“…Although the above studies were conducted under different protocols, such that simple comparisons are not feasible, the results of our current study suggest higher efficacy of F-RVCZ for onychomycosis as compared with the complete cure rates achieved in previous clinical studies of drugs for onychomycosis. [15][16][17] The subgroup analysis results according to age (<65 or ≥65 years), sex, fungal species and nail involvement ratio at screening (<50% or Blood alkaline phosphatase increased ≥50%) demonstrated significantly higher efficacy of F-RVCZ than placebo in all subgroups, suggesting substantial efficacy of F-RVCZ regardless of baseline patient characteristics. In our current study, the complete cure rate with F-RVCZ gradually increased over time and became significantly different compared with placebo from the time point of week 36 onward.…”

“…They reported that the complete cure rate was 23.4% after 72 weeks of pulse therapy consisting of three cycles of 400 mg/day of itraconazole administrated for 7 days followed by a 21‐day washout, and 45.8% at 72 weeks after initiation of treatment with 250 mg/day of terbinafine continuously administrated for 12 weeks. In phase III studies of efinaconazole and luliconazole, topical drugs indicated for onychomycosis that recently became available in Japan, conducted in patients with mild to moderate onychomycosis with a nail involvement ratio of 20–50%, the complete cure rates after 48 weeks of once‐daily topical administration were 17.8% and 15.2% for efinaconazole (at week 52, data from two different studies) and 14.9% for luliconazole (at week 48) . Given these relatively low rates, demand persisted for the development of an oral antifungal agent with a high cure rate …”

“…In phase III studies of efinaconazole and luliconazole, topical drugs indicated for onychomycosis that recently became available in Japan, conducted in patients with mild to moderate onychomycosis with a nail involvement ratio of 20-50%, the complete cure rates after 48 weeks of oncedaily topical administration were 17.8% and 15.2% for efinaconazole (at week 52, data from two different studies) 16 and 14.9% for luliconazole (at week 48). 17 Given these relatively low rates, demand persisted for the development of an oral antifungal agent with a high cure rate. 2 Our current phase III study of F-RVCZ included patients with onychomycosis, some of whom had a mean nail involvement ratio of 54.51% or more.…”

Topical efinaconazole: A promising therapeutic medication for tinea unguium

“…In 2014, efinaconazole 10% topical solution was approved as a prescription drug by the Pharmaceuticals and Medical Devices Agency of Japan. In 2016, luliconazole 5% nail solution was also approved . These topical medications now serve as a new therapeutic method for preventing adverse reactions such as liver damage and drug–drug interaction in elderly patients as well as in patients with complications and underlying diseases.…”