nnd-502 and Tinea

We evaluated the efficacy and safety of luliconazole cream 1% in the treatment of dermatophytoses. According to our meta-analysis, short-term treatment of luliconazole cream 1% can result in the complete clearance of dermatophytoses. It showed that 1% luliconazole was more effective than controlled drugs or vehicle (week 4: odds ratio = 1.46, 95% confidence interval = 1.12-1.91), and no more adverse events occurred in the 1% luliconazole group (week 4: odds ratio = 1.01, 95% confidence interval = 0.71-1.44). This effect strengthens the evidence for luliconazole cream 1% being more effective than vehicle, 1% terbinafine, 1% bifonazole, and 0.1% or 0.5% luliconazole.

Topics: Humans; Imidazoles; Randomized Controlled Trials as Topic; Skin Cream; Tinea

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.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Imidazoles; Japan; Male; Microscopy; Middle Aged; Onychomycosis; Pharmaceutical Solutions; Tinea; Treatment Outcome; Trichophyton; Young Adult

Tinea cruris, a pruritic superficial fungal infection of the groin, is the second most common clinical presentation for dermatophytosis.. This phase 3 study evaluated the safety and efficacy of topical luliconazole cream 1% in patients with tinea cruris.. 483 patients were enrolled and 256 male and female patients aged ≥12 years with clinically evident tinea cruris and eligible for modified intent-to-treat analysis were randomized 2:1 to receive luliconazole cream 1% (n=165) or vehicle (n=91) once daily for 7 days. Efficacy was evaluated at baseline and at days 7, 14, 21, and 28 based on mycology (potassium hydroxide, fungal culture) and clinical signs (erythema, scaling, pruritus). The primary outcome was complete clearance at day 28 (21 days posttreatment). Safety evaluations included adverse events and laboratory assessments.. Complete clearance was obtained in 21.2% (35/165) of patients treated with luliconazole cream 1% compared with 4.4% (4/91) treated with vehicle (P<0.001). The safety profile of luliconazole cream 1% was similar to vehicle.. The study was conducted under controlled conditions in a relatively small population.. Luliconazole cream 1% applied once daily for 7 days is more effective than vehicle and well tolerated in patients with tinea cruris.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Double-Blind Method; Female; Fungi; Humans; Imidazoles; Male; Microbial Sensitivity Tests; Middle Aged; Ointments; Tinea; Treatment Outcome; Young Adult

An efficacious period of two topical antifungal drugs was compared in a Trichophyton mentagrophytes-infected onychomycosis model in guinea pigs treated with antifungal drugs prior to infection. Luliconazole 5% (LLCZ) and efinaconazole 10% (EFCZ) test solutions were applied to the animals' nails once daily for 2 weeks followed by a nontreatment period of 2, 4, and 8 weeks. After each nontreatment period, the nails were artificially infected by the fungus. Drug efficacy was quantitatively evaluated by qPCR and histopathological examination of the nails collected following a 4-week post-infection period. The fungal infection was confirmed in the untreated group. Both LLCZ and EFCZ prevented fungal infection in the treated groups with the nontreatment period of 2 weeks. After the nontreatment period of 4 weeks, no infection was observed in the LLCZ-treated group; however, infection into the nail surface and fungal invasion into the nail bed were observed in the EFCZ-treated group. After the nontreatment period of 8 weeks, fungi were found in the nail surface and nail bed in some nails treated with EFCZ; however, no infection was observed in the nail bed of the LLCZ-treated group. The results suggest that LLCZ possesses longer-lasting antifungal effect in nails of the guinea pigs than EFCZ, and that this animal model could be useful for translational research between preclinical and clinical studies to evaluate the pharmacological efficacy of antifungal drugs to treat onychomycosis. This experimentally shown longer-lasting preventive effects of LLCZ could also decrease the likelihoods of onychomycosis recurrence clinically.

Topics: Administration, Topical; Animals; Antifungal Agents; Disease Models, Animal; Guinea Pigs; Imidazoles; Male; Specific Pathogen-Free Organisms; Tinea; Triazoles; Trichophyton

Dermatophytes are a group of keratinophilic fungi that invade and infect the keratinized tissues and cause dermatophytosis. We investigated effectiveness of novel triazole (luliconazole and lanaconazole) in comparison with available antifungal agents against dermatophyte species isolated from patients with tinea pedis.. A total of 60 dermatophytes species were isolated from the patients with tinea pedis. Identification of species was done by DNA sequencing of the ITS1-5.8S rDNA-ITS2 rDNA region. In vitro antifungal susceptibility testing with luliconazole and lanaconazole and available antifungal agent was done in accordance with the Clinical and Laboratory Standards Institute, M38-A2 document.. In all investigated isolates, luliconazole had the lowest minimum inhibitory concentration (MIC) (MIC range=0.0005-0.004μg/mL), while fluconazole (MIC range=0.4-64μg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008μg/mL), followed by lanoconazole (0.003μg/mL), terbinafine (0.019μg/mL), itraconazole (0.085 μg/mL), ketoconazole (0.089μg/mL), econazole (0.097μg/mL), griseofulvin (0.351 μg/mL), voriconazole (0.583μg/mL) and fluconazole (11.58μg/mL).. The novel triazoles showed potent activity against dermatophytes and promising candidates for the treatment of tinea pedis caused by Trichophyton and Epidermophyton species. However, further studies are warranted to determine the clinical implications of these investigations.

Topics: Antifungal Agents; Arthrodermataceae; Dermatomycoses; Fluconazole; Griseofulvin; Humans; Imidazoles; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Terbinafine; Tinea; Tinea Pedis; Triazoles; Trichophyton; Voriconazole

Tinea are superficial fungal infections caused by dermatophytes. Luliconazole exhibits highest antifungal activity against Trichophyton spp. which are major causative agents of dermatophytosis. However, luliconazole suffers from drawbacks such as less skin retention, low aqueous solubility and poor skin penetration. To overcome the limitations of luliconazole, nanostructured lipid carriers (NLCs) were formulated. NLCs are better permeation enhancers as they increase skin occlusion and hydration. The selection of various lipids and surfactants was based on the solubility of luliconazole in these components. Luliconazole NLC dispersion was prepared by hot melt emulsification technique followed by probe sonication. The dispersion was incorporated into a gel composed of Sepineo P 600 under magnetic stirring. in vitro antifungal studies were carried out with optimized luliconazole NLC gel, marketed luliconazole cream and control (luliconazole in gel base) against pathogenic Trichophyton rubrum. Ex-vivo diffusion study demonstrated that NLCs incorporated into gel exhibited greater retention on skin. In-vivo skin irritancy study showed no signs of erythema or edema post 24, 48, and 72 h at site of application. In comparison with marketed cream and based on the zone of inhibition diameters, NLC formulation was found to be very effective against Trichophyton rubrum.

Topics: Arthrodermataceae; Humans; Imidazoles; Lipids; Skin; Tinea

A 26-year-old female homemaker presented with an approximately 2-month history of an erythematous lesion with agminated seropapules in the right popliteal fossa associated with scales and crusts. The lesion was initially treated as contact dermatitis, but there was no improvement. KOH examination revealed filamentous fungi. The fungal culture was positive, and the morphological characteristics were identical to those of Trichophyton mentagrophytes complex. The fungus was identified as T. erinacei based on genetic analysis. This is the second case report of human tinea corporis due to this fungus in Japan.

Topics: Adult; Animals; Antifungal Agents; Female; Genotype; Hedgehogs; Humans; Imidazoles; Itraconazole; Japan; Pets; Pulse Therapy, Drug; Tinea; Treatment Outcome; Trichophyton; Zoonoses

We cultured 15 isolates of Trichophyton rubrum and one isolate of Trichophyton mentagrophytes from an 82-year-old male tinea patient with multiple lesions. To determine whether feet lesions were the source of dermatophytes of other tinea lesions, we extracted total cellular DNA from the T. rubrum isolates（13 from feet, two from right waist and buttock）. PCR targeting the non-transcribed spacer（NTS）region of ribosomal RNA gene was performed. Molecular polymorphisms were detected by length variation of amplicons.Four molecular types were found among the 15 isolates. The predominant type, which we previously named Type III, comprised seven isolates cultured from both feet and from left waist and buttock. This was followed by Type VI, five isolates; Type V, two isolates; and Type IV, one isolate. Apart from type III, which was cultured from both feet, isolates were cultured from one foot only. The patient was successfully treated for all types with a six-month course of oral terbinafine and topical luliconazole. The molecular typing supported the notion that tinea pedis was the source of tinea corporis in the patient.

Topics: Administration, Oral; Administration, Topical; Aged, 80 and over; Buttocks; DNA, Fungal; Foot; Humans; Imidazoles; Male; Naphthalenes; Polymerase Chain Reaction; Polymorphism, Genetic; RNA, Ribosomal; Skin; Terbinafine; Tinea; Treatment Outcome; Trichophyton

Onychomycosis and tinea pedis are common fungal infections affecting the nails and feet, respectively. Two newly approved topical agents for onychomycosis are efinaconazole and tavaborole, both of which have demonstrated respectable cure rates in clinical studies. For tinea pedis, naftifine 2% and luliconazole 1% are new agents, both administered for relatively short courses, that may foster greater adherence Semin Cutan Med Surg 35(supp6):S110-S113.

Topics: Administration, Cutaneous; Antifungal Agents; Humans; Imidazoles; Onychomycosis; Recurrence; Tinea; Tinea Pedis; Triazoles

Scales from lesional skin of 12 patients with tinea pedis were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to gain an insight into the spatial and morphological changes of dermatophytes after application of a clinical dosage of topical luliconazole 1% cream (Lulicon® cream 1%). In all cases, Trichophyton rubrum was identified. The scales from the lesions collected before and after topical luliconazole application were fixed with glutaraldehyde and subjected to SEM and TEM. For SEM, fixed specimens were first placed in 1N-KOH and then post-fixed and observed. SEM showed a swollen appearance of fungal hyphae as an early change, and then shrinkage of them showing a flattened and twisted appearance as a later change. TEM showed cell wall alterations with initial development of and accumulation of a granular structure in the outermost layer and subsequent amorphous and electron-lucent change of the thickened inner part of the cell wall. This is the first report of dramatic morphological changes of T. rubrum before and after topical luliconazole application in vivo demonstrated by SEM and TEM. We hypothesize that luliconazole has double acting points, on the plasma membrane and cell wall, of dermatophyte hyphae.

Topics: Antifungal Agents; Humans; Hyphae; Imidazoles; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Specimen Handling; Tinea; Trichophyton

Luliconazole is a novel topical antifungal imidazole with broad-spectrum and potent antifungal activity. The drug is under clinical development in the United States for management of dermatophytosis with a short-term treatment regimen. The present study was undertaken to investigate the clinical benefit of short-term therapy with luliconazole cream in guinea pig models of tinea corporis and tinea pedis induced with Trichophyton mentagrophytes. The dose-dependent therapeutic efficacy of topical luliconazole cream (0.02 to 1%), measured by macroscopic improvement of skin lesions and by fungal eradication as determined by a culture assay, was demonstrated using a tinea corporis model. The improvement in skin lesions seen with luliconazole cream was observed even at a concentration of 0.02%, and its efficacy at 0.1% was equal to that of 1% bifonazole cream. The efficacy of short-term therapy with 1% luliconazole cream, which is used for clinical management, was investigated using the tinea corporis model (4- and 8-day treatment regimens) and the tinea pedis model (7- and 14-day treatment regimens). The 1% luliconazole cream completely eradicated the fungus in half or less of the treatment time required for 1% terbinafine cream and 1% bifonazole cream, as determined by a culture assay for both models. These results clearly indicate that 1% luliconazole cream is sufficiently potent for short-term treatment for dermatophytosis compared to existing drugs. Luliconazole is expected to be useful in the clinical management of dermatophytosis.

Topics: Animals; Antifungal Agents; Guinea Pigs; Imidazoles; Tinea; Tinea Pedis