nnd-502 and Tinea-Pedis

Luliconazole is an imidazole antifungal agent with a unique chemical structure. In this article, we summarize the in vitro data, animal studies and clinical trial data relating to the use of topical luliconazole cream 1% in the treatment of tinea pedis. Preclinical studies have demonstrated potent activity against dermatophytes. Luliconazole has strong fungicidal activity against Trichophyton spp., similar to that seen with terbinafine. Evidence from clinical trials in tinea pedis have shown once-daily application of luliconazole cream 1% for 14 days to be effective and well tolerated.

Topics: Administration, Cutaneous; Animals; Antifungal Agents; Clinical Trials as Topic; Drug Administration Schedule; Drug Evaluation, Preclinical; Humans; Imidazoles; Tinea Pedis; Treatment Outcome

Approximately 20-25% of the population worldwide is affected by superficial cutaneous mycoses (SCM). SCM are cutaneous fungal infections with a wide array of systemic and topical treatment options. However, successful therapeutic outcomes are limited by patient non-adherence, medication side effects, potential drug interactions, antifungal resistance and disease recurrence. Advances in formulation technology have allowed for the development of more effective and safer therapies. In this article we will review several new and emerging pharmacotherapeutics for onychomycosis and tinea pedis.

Topics: Allylamine; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Education, Medical, Continuing; Humans; Imidazoles; Itraconazole; Onychomycosis; Tinea Pedis; Triazoles

Interdigital tinea pedis is one of the most common clinical presentations of dermatophytosis.. This phase 3 study evaluated the safety and efficacy of luliconazole cream 1% in patients with tinea pedis.. A total of 321 male and female patients aged ≥12 years with tinea pedis and eligible for modified intent-to-treat analysis were randomized 1:1 to receive luliconazole cream 1% (n=159) or vehicle (n=162) once daily for 14 days. Efficacy was evaluated at days 28 and 42 (i.e., days 14 and 28 posttreatment) based on clinical signs (erythema, scaling, pruritus) and mycology (KOH, fungal culture). The primary outcome was complete clearance at day 42. Safety evaluations included adverse events and laboratory assessments.. Complete clearance at day 42 was achieved in 26.4% (28/106) of patients treated with luliconazole cream 1% compared with 1.9% (2/103) of patients treated with vehicle (P< 0.001). Similar safety profiles were obtained for luliconazole cream 1% and vehicle.. This study was conducted in a relatively small population under controlled clinical trial conditions.. Luliconazole cream 1% applied once daily for 14 days is well tolerated and more effective than vehicle in patients with tinea pedis.

Topics: Administration, Topical; Adult; Antifungal Agents; Double-Blind Method; Female; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Time Factors; Tinea Pedis; Treatment Outcome; Young Adult

Tinea pedis (TP) typically is treated with topical antifungal agents. Luliconazole, a novel imidazole drug, is shown to be as or more effective in vitro and in vivo than bifonazole, terbinafine, and lanoconazole. Two treatment durations with luliconazole cream 1% were evaluated for treatment of TP. Participants with interdigital TP were randomized (N= 147) and treated with either luliconazole or its vehicle for either 2 or 4 weeks. The primary efficacy end point was the proportion of participants achieving complete clearance 2 weeks following completion of treatment. In the 2-week active treatment group, complete clearance was achieved in 26.8% (11/41) of participants versus 9. 1% (2/22) in the 2-week vehicle group at 2-weeks posttreatment. In the 4-week active treatment group, 45.7% (16/35) achieved complete clearance versus 10.0% (2/20) in the 4-week vehicle group at 2-weeks posttreatment. Twenty-three adverse events (AEs) were reported; most were mild (56.5% [13/23]) to moderate (26. 1% [6/23]) in severity. All reported AEs were determined to be unrelated (78.3% [18/23]) or unlikely related (21.7% [5/23]) to the study medication. The results of this study indicate that luliconazole cream 1% applied once daily for either 2 or 4 weeks is safe and effective for treatment of TP. More importantly, the antifungal effects of luliconazole persist for several weeks, resulting in increased rates of mycological cure.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Antifungal Agents; Child; Double-Blind Method; Female; Humans; Imidazoles; Male; Middle Aged; Severity of Illness Index; Time Factors; Tinea Pedis; Treatment Outcome; Young Adult

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

The viability of pathogenic fungi in the scale was investigated during topical administration of 1% luliconazole (LLCZ). Thirteen tinea pedis patients found to be positive on KOH examination were assessed by mycological examinations and quantitative real-time polymerase chain reaction (PCR) targeted internal transcribed spacer (ITS) in ribosomal RNA gene at the initial visit and after 2 and 4 weeks of treatment. Assays showed that the average copy number of ITS DNA had significantly decreased to 22.9% at 2 weeks and 4.8% at 4 weeks compared with the initial visit. LLCZ topical treatment could defeat almost pathogenic dermatophytes in the scales within 4 weeks.

Topics: Administration, Topical; Aged; Aged, 80 and over; Antifungal Agents; Arthrodermataceae; DNA, Intergenic; Female; Humans; Imidazoles; Male; Microbial Viability; Middle Aged; Tinea Pedis; Treatment Outcome

To compare drug concentrations in the stratum corneum following daily application of luliconazole and terbinafine cream in a guinea pig tinea pedis model.. Luliconazole 1% cream or terbinafine 1% cream were topically applied once daily to hind limbs of guinea pigs for 14 days. Drug concentration in stratum corneum of plantar skin was measured by HPLC-UV on days 1, 3, 7, 10, and 14. Separately, creams were applied daily for 5 days to the hind limbs of guinea pigs and skin drug release determined. In addition, drug retention in the stratum corneum was assessed by infecting guinea pigs with Trichophyton mentagrophytes, 14 and 21 days after a single application of luliconazole or terbinafine creams.. Luliconazole stratum corneum concentrations were higher than those of terbinafine throughout the study. Concentrations of luliconazole and terbinafine were 71.6μg/g and 36.6μg/g, respectively, after a single application (P<.05), reaching steady state after 10 days. Cumulative release of luliconazole from the stratum corneum was 4.5 times greater than with terbinafine. Unlike terbinafine, no fungal invasion of the stratum corneum was seen 14 days post-treatment with luliconazole.. Drug concentrations of luliconazole in the stratum corneum and subsequent release are greater than those achieved with terbinafine and may contribute to clinical efficacy. Luliconazole may also provide greater protection against disease recurrence.

Topics: Animals; Antifungal Agents; Disease Models, Animal; Epidermis; Guinea Pigs; Imidazoles; Male; Tinea Pedis

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

Topics: Antifungal Agents; Drug Approval; Humans; Imidazoles; Randomized Controlled Trials as Topic; Tinea Pedis

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

Topics: Allergens; Antifungal Agents; Dermatitis, Allergic Contact; Diagnosis, Differential; Female; Foot Dermatoses; Humans; Imidazoles; Middle Aged; Patch Tests; Tinea Pedis

Topics: Animals; Antifungal Agents; Guinea Pigs; Humans; Imidazoles; Malassezia; Tinea Pedis; Trichophyton

We examined the therapeutic effect of a 1% cream preparation of NND-502, a novel topical antifungal agent, in a guinea pig tinea pedis model produced by infecting the plantar skin of guinea pigs with Trichophyton mentagrophytes. Animals developing tinea pedis were divided into two groups: an untreated control group and a treated group. In the latter group, after confirming infection had been established, the infected animals were topically treated with the NND-502 cream once daily for one week. The animals were reared in a clean environment free from exposure to exogenous dermatophytes. At one week (5 weeks post-infection), 6 weeks (10 weeks post-infection) and 16 weeks (20 weeks post-infection) after completion of the treatment, plantar skin samples were taken from a certain number of both groups of animals. The results demonstrated that all of the animals in the untreated control group and none of those in the treated group were culture-positive in this animal model of tinea pedis. The topical treatment with NND-502 achieved a mycological cure. Thus NND-502 can be considered a promising candidate as a new anti-dermatophytic agent for topical use.

Topics: Administration, Topical; Animals; Antifungal Agents; Culture Media; Disease Models, Animal; Female; Guinea Pigs; Imidazoles; Skin; Tinea Pedis; Treatment Outcome; Trichophyton

In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole antimycotic agent, were compared with those of two existing antifungal agents, lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal activity against Trichophyton spp.; its MIC was 1 to 4 times lower than that of lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in polyethylene glycol 400) was more effective than that with a 0.5% solution of either lanoconazole or terbinafine for eradicating fungi from the infected feet. When the duration of treatment was shortened to 3 days, a topical 1% solution of NND-502 achieved a complete mycological cure, while topical 1% solutions of lanoconazole and terbinafine did not.

Topics: Animals; Antifungal Agents; Arthrodermataceae; Dermatomycoses; Guinea Pigs; Imidazoles; Microbial Sensitivity Tests; Tinea Pedis