Safety and Tolerability of Luliconazole Solution 10-Percent in Patients with Moderate to Severe Distal Subungual Onychomycosis

Jones, Terry M.; Tavakkol, Amir

doi:10.1128/aac.02370-12

Cited by 38 publications

(25 citation statements)

References 14 publications

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“…5,17,28,29 Skin irritation indices have been reported to be within the range specified for a safe product. 5 No toxicity issues have been reported in guinea pig model studies of tinea pedis induced with T. mentagrophytes.…”

Section: Safety and Tolerabilitymentioning

confidence: 96%

“…17 In this study, luliconazole showed very low systemic absorption and excellent local tolerability with no evidence of laboratory abnormalities or subject discontinuation, 33 with plasma concentrations near or below the lower limit of quantification (0.05 ng ml À1 ). 17 In contrast, median nail concentration of luliconazole 7 days after the last application was 35 mg g À1 ; 17 thousands of times greater than the MIC90 of T. rubrum and T. mentagrophytes (0.001 lg ml À1 ). 4 Very low levels of luliconazole were measurable in plasma up to 7 days after the last application, indicating that the nail plate may serve as a reservoir allowing its slow release into the nail bed.…”

Section: Clinical Experience In Onychomycosismentioning

confidence: 97%

See 1 more Smart Citation

Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis

Scher

Nakamura²,

Tavakkol³

2014

Mycoses

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Luliconazole is a novel, broad-spectrum, imidazole antifungal under development in the USA as a treatment for dermatophytic skin and nail infections. In vitro, luliconazole is one of the most potent antifungal agents against filamentous fungi including dermatophytes. Luliconazole has been formulated in a 10% solution with unique molecular properties, which allow it to penetrate the nail plate and rapidly achieve fungicidal levels in the nail unit. These properties make luliconazole a potent compound in the treatment of onychomycosis. This article reviews the development of luliconazole solution, 10% its molecular properties, preclinical and clinical data and its future perspectives for the treatment of fungal infections.

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Section: Safety and Tolerabilitymentioning

confidence: 96%

Section: Clinical Experience In Onychomycosismentioning

confidence: 97%

Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis

Scher

Nakamura²,

Tavakkol³

2014

Mycoses

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“…Luliconazole is a novel imidazole currently under development. Pharmacokinetic and safety results from phase 1 studies in patients with onychomycosis have demonstrated high concentrations of luliconazole within the nail plates of the great toe and have shown that this agent is well tolerated when administered as a 10% solution (7). In vitro studies with a limited number of isolates have also reported potent activity of this agent against dermatophytes and other causative agents of dermatophytosis, including onychomycosis (8)(9)(10).…”

mentioning

confidence: 99%

Luliconazole Demonstrates Potent In Vitro Activity against Dermatophytes Recovered from Patients with Onychomycosis

Wiederhold

Fothergill

McCarthy

et al. 2014

Antimicrob Agents Chemother

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The in vitro activities of luliconazole, amorolfine, ciclopirox, and terbinafine were determined against 320 dermatophyte isolates from large toenails of onychomycosis patients enrolled into an ongoing phase 2b/3 clinical study. The geometric mean MIC for luliconazole was 0.00022 g/ml against all isolates, compared to 0.0194 to 0.3107 g/ml for the three other agents. The in vitro potency of luliconazole was maintained regardless of the dermatophyte species.O nychomycosis (tinea unguium) is a fungal infection of the nail bed and or plate and is associated with significant morbidity (1). Besides causing cosmetic concerns, this mycosis can result in pain or discomfort, acute bacterial cellulitis associated with spread of infection to the skin, and social stigma (2, 3). The prevalence of onychomycosis is estimated to be between 2 and 14%, with a rate of 13.8% reported in North America (1, 4). Risk factors for infection include increasing age, male gender, dystrophic nails, tinea pedis, and poor peripheral circulation (1, 3, 4). These infections are caused primarily by dermatophytes, including Trichophyton rubrum and T. mentagrophytes, and to a lesser extent by other dermatophytes (e.g., Epidermophyton floccosum), Candida species, and nondermatophytic molds (e.g., Acremonium, Fusarium, and Scopulariopsis species) (5, 6). Luliconazole is a novel imidazole currently under development. Pharmacokinetic and safety results from phase 1 studies in patients with onychomycosis have demonstrated high concentrations of luliconazole within the nail plates of the great toe and have shown that this agent is well tolerated when administered as a 10% solution (7). In vitro studies with a limited number of isolates have also reported potent activity of this agent against dermatophytes and other causative agents of dermatophytosis, including onychomycosis (8-10). Results from animal models and small clinical studies have also suggested in vivo efficacy against dermatophytosis (11-13). Our objective was to measure the in vitro activity of luliconazole against dermatophytes isolated at screening from toenails in an ongoing phase 2b/3 study of patients with mild to moderate toenail onychomycosis (www.clinicaltrials.gov, identifier NCT01431820). In addition, the in vitro activities of amorolfine, ciclopirox, and terbinafine, three products approved and most often used for treatment of onychomycosis in the United States and the European Union, were also determined.Three hundred twenty dermatophytes obtained from patients with confirmed toenail onychomycosis (positive KOH and culture and clinical diagnosis) during screening were used in this study. This included 308 Trichophyton rubrum and 10 T. mentagrophytes isolates and one each of Trichophyton tonsurans and Epidermophyton floccosum. All isolates were clinical strains that had been freshly subcultured and not previously frozen. Stock solutions of amorolfine, ciclopirox, terbinafine, and luliconazole were prepared in dimethyl sulfoxide (DMSO) and further diluted in RPMI 1640 buffered to a...

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“…Other formulations with terbinafi ne that are undergoing phase II trials include MOB-015 and TMI-358. Luliconazole has completed phase I and IIa testing for treatment of moderate to severe distal subungual onychomycosis with positive results (Jones and Tavakkol 2013 ). Refer to Table 21.1 for a comprehensive list of new topical antifungal treatment options for onychomycosis.…”

Section: Topical Treatmentmentioning

confidence: 99%

Dermatophyte Infections

Tosti¹,

Shaurya²,

Piraccini³

2015

European Handbook of Dermatological Treatments

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Safety and Tolerability of Luliconazole Solution 10-Percent in Patients with Moderate to Severe Distal Subungual Onychomycosis

Cited by 38 publications

References 14 publications

Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis

Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis

Luliconazole Demonstrates Potent In Vitro Activity against Dermatophytes Recovered from Patients with Onychomycosis

Dermatophyte Infections

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