Activity of amorolfine or ciclopirox in combination with terbinafine against pathogenic fungi in onychomycosis-Results of an in vitro investigation.

BACKGROUND: Onychomycoses are difficult-to-treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. OBJECTIVES: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. METHODS: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96-well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. RESULTS: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. CONCLUSIONS: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non-dermatophyte fungus such as S. brevicaulis.

Resistance Profile, Terbinafine Resistance Screening and MALDI-TOF MS Identification of the Emerging Pathogen Trichophyton indotineae.

The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains.

In vitro anti-Pythium insidiosum activity of amorolfine hydrochloride and azithromycin, alone and in combination.

Pythium insidiosum infections have been widely studied in an attempt to develop an effective therapeutic protocol for the treatment of human and animal pythiosis. Several antifungal agents are still prescribed against this oomycete, although they present contradictory results. To evaluate the susceptibility profile and to verify the morphological alterations in P. insidiosum isolates treated with amorolfine hydrochloride and azithromycin, alone or in combination. Susceptibility tests for P. insidiosum isolates (n = 20) against amorolfine hydrochloride (AMR) and azithromycin (AZM) were performed according to Clinical and Laboratory Standards Institutes (CLSI) protocol M38-A2. Combinations of both drugs were evaluated using the checkerboard microdilution method. Additionally, transmission and scanning electron microscopy were performed in order to verify the morphological alterations in P. insidiosum isolates in response to these drugs. All P. insidiosum isolates had a minimum inhibitory concentration (MIC) ranging from 16 to 64 mg/l and 8 to 64 mg/l for amorolfine hydrochloride and azithromycin, respectively. Synergistic interactions between the drugs were not observed, with antagonism in 59.8% of isolates, and indifferent interactions in 36.2%. Electron microscopy showed changes in the surface of P. insidiosum hyphae, disorganization of intracellular organelles, and changes in the plasma membrane and cell wall of oomycetes treated with the drugs. This is the first study to demonstrate in vitro anti-P. insidiosum effect of amorolfine hydrochloride. These results indicate the therapeutic potential of this drug against cutaneous and subcutaneous forms of pythiosis, but further studies are necessary to confirm this potential.

Effect of onychomycosis and treatment on patient-reported quality-of-life outcomes: A systematic review.

BACKGROUND: Onychomycosis is the most common nail disorder, often causing physical, emotional, and aesthetic consequences. The effect of both the condition itself and treatment on quality of life has not been well studied. OBJECTIVE: The objectives of this study were to systematically review the available literature describing the effect of onychomycosis and treatment on quality of life. METHODS: We performed a search of the onychomycosis literature published before April 13, 2020. Articles were included in the review if primary data were presented, patient-reported outcome measures were used, and onychomycosis was specifically examined. RESULTS: Thirty studies were included in the final analysis. Poorest quality-of-life scores were associated with women and fingernail involvement. Quality-of-life scores improved from baseline with all treatment types; there were greater improvements reported with oral treatments compared with topical ones. CONCLUSIONS: This review affirms that onychomycosis significantly influences quality of life, warranting effective treatment. All treatments resulted in quality-of-life improvements; however, studies on oral and topical therapies were of higher quality than those evaluating devices. Increased efforts are needed to understand the effect of the disease and therapy as assessed by validated, nail-specific outcome measures that accurately assess patients' cosmetic, physical, and social difficulties.

Methylene blue-mediated photodynamic therapy may be superior to 5% amorolfine nail lacquer for non-dermatophyte onychomycosis.

BACKGROUND: Methylene blue-mediated photodynamic therapy as an antimicrobial has been reported to improve onychomycosis. OBJECTIVES: To compare the short-term efficacy of methylene blue-mediated photodynamic therapy (MB-PDT) and 5% amorolfine nail lacquer (AMO) for toenail onychomycosis using higher intensity and shorter total treatment period than previously reported. METHODS: Twenty-seven toenails with onychomycosis were randomized to receive either six biweekly sessions of MB-PDT or AMO for twelve weeks. Dermoscopic photography was used for onychomycosis severity index assessment under a dermoscopic inspection (d-OSI) at baseline, weeks 6, 10, 14 and 22 as well as microscopic and microbiological tests. Adverse events were recorded. RESULTS: All subjects completed the study. Causative organisms found were exclusively non-dermatophytes including Fusarium spp., Asperillus spp.,and yeasts. Fifteen toenails received MB-PDT, whilst 12 received AMO. D-OSI showed greater improvement in MB-PDT than in AMO groups at weeks 6, 10, 14 as well as 22, with median changes of -2, -3, -4 (P = .055). and - 3 respectively in the MB-PDT group. The AMO group displayed the median d-OSI change of 0 throughout the study period. Mycological cure rate at 22 weeks in MB-PDT and AMO group was 73.3% and 66.67% (P > .05). Clinical cure rate at 22 weeks in MB-PDT (26.7%) was higher than AMO (16.7%), (P > .05). All patients only felt comfortably warm during the MB-PDT treatment. No major adverse events were found in both groups. CONCLUSIONS: MB-PDT appeared to be more efficacious for non-dermatophyte onychomycosis than AMO particularly in a limited period and moderately severe onychomycosis.

Comparison of a fractional 2940-nm Er:YAG laser and 5% amorolfine lacquer combination therapy versus a 5% amorolfine lacquer monotherapy for the treatment of onychomycosis: a randomized controlled trial.

Onychomycosis is a fungal infection of the nail. The aim of this randomized controlled clinical trial was to compare the efficacy of 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer versus amorolfine monotherapy for treating onychomycosis. In this study, patients with onychomycosis of the great toenail were randomly assigned to a combination therapy group and a monotherapy group. In the combination therapy group, the included toenails were treated with a fractional 2940-nm Er:YAG laser at weeks 1, 2, 3, 4, 8, and 12, combined with a 5% amorolfine lacquer twice a week for 12 weeks, while in the monotherapy group, the included toenails were treated with only a 5% amorolfine lacquer twice a week for 12 weeks. The onychomycosis severity index (OSI) score and the mycological clearance rate (MCR) of the included toenails were assessed at baseline, week 12, and week 24. At weeks 12 and 24, the great toenails with mild and moderate onychomycosis in the combination therapy group showed obvious improvement and a greater decrease in OSI than those in the monotherapy group. At week 24, the toenails with mild and moderate onychomycosis in the combination therapy group also showed a better MCR. For the toenails with severe onychomycosis, little improvement was observed in either group at week 12 or week 24. In conclusion, fractional 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer is more effective than amorolfine monotherapy in short-term improvement of onychomycosis.

Interaction Between Amorolfine and Voriconazole Against Fusarium species.

Fusarium species represent a range of fungal pathogens capable of causing diverse mycotic diseases. Relative to antibacterial drugs, few effective antifungal agents have been developed to date, and all are subject to significant limitations. As such, there is an urgent need to design novel antifungal treatments for infections caused by Fusarium spp. Herein, 15 clinical isolates, including 5 Fusarium oxysporum and 10 Fusarium solani strains, were analyzed to explore the relative inhibitory effects of different combinations of amorolfine (AMO) and voriconazole (VOR) on the growth of these fungal pathogens. These analyses were conducted by measuring minimal inhibitory concentration (MIC) values for these antifungal agents in a broth microdilution assay and by using an in vivo model of Fusarium-infected Galleria mellonella. These experiments revealed that in isolation, AMO and VOR exhibited MIC values ranging from 4 to 16 µg/mL and 2 to 8 µg/mL, respectively. However, these effective MIC values fell to 1-2 µg/mL and 0.5-2 µg/mL, respectively, when AMO and VOR were administered in combination with one another, exhibiting synergistic activity against 73.3% of analyzed Fusarium strains. Subsequent in vivo analyses conducted using the G. mellonella model further confirmed that combination VOR + AMO treatment was associated with significantly improved larval survival following Fusarium spp. infection. Together, these results serve as the first published evidence demonstrating that VOR and AMO exhibit synergistic activity against infections caused by Fusarium spp., indicating that they may represent an effective approach to antifungal disease treatment.

Visualisation of penetration of topical antifungal drug substances through mycosis-infected nails by matrix-assisted laser desorption ionisation mass spectrometry imaging.

BACKGROUND: Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) is a mass spectrometry-based technique, which can be applied for compound-specific imaging of pharmaceuticals in tissues samples. MALDI-MSI technology is widely used to visualise penetration and distribution profile through different tissues but has never been used with nail tissue. OBJECTIVES: This study used MALDI-MSI technology to visualise distribution profile and penetration into ex vivo human mycosis-infected toenails of three antifungal active ingredients amorolfine, ciclopirox and naftifine contained in topical onychomycosis nail treatment preparations, marketed as Loceryl® , Ciclopoli® and Exoderil® . METHODS: Three mycosis-infected toenails were used for each treatment condition. Six and twenty-four hours after one single topical application of antifungal drugs, excess of formulation was removed, nails were cryo-sectioned at a thickness of 20 µm, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analysed by MALDI-MSI. RESULTS: All antifungal actives have been visualised in the nail by MALDI-MSI. Ciclopirox and naftifine molecules showed a highly localised distribution in the uppermost layer of the nail plate. In comparison, amorolfine diffuses through the nail plate to the deep layers already 6 hours after application and keeps diffusing towards the lowest nail layers within 24 hours. CONCLUSIONS: This study shows for the first-time distribution and penetration of certain antifungal actives into human nails using MALDI-MSI analysis. The results showed a more homogeneous distribution of amorolfine to nail and a better penetration through the infected nails than ciclopirox and naftifine.

A pilot, layerwise, ex vivo evaluation of the antifungal efficacy of amorolfine 5% nail lacquer vs other topical antifungal nail formulations in healthy toenails.

BACKGROUND: Studies investigating the penetration of amorolfine through the nail have shown the highest concentration in the uppermost layer and measurable antifungal activity even in the lower layers of the nail. OBJECTIVES: This pilot, ex vivo study compared the penetration of antifungal concentrations of amorolfine 5% nail lacquer in different layers of healthy, human cadaver toenails with that of terbinafine 10% nail solution, ciclopirox 8% nail lacquer and naftifine 1% nail solution. Moreover, the effect of nail filing prior to application on the penetration of amorolfine 5% was assessed. METHODS: Unfiled (n = 3) and filed (n = 3) nails were used for each antimycotic agent and amorolfine 5% nail lacquer, respectively. Twenty-four hours after topical application, the nails were sliced (10 µm), solubilised and added to agar plates seeded with Trichophyton rubrum. Zones of growth inhibition were measured. RESULTS: Only amorolfine penetrated the nails at sufficient concentrations to inhibit growth of T rubrum at different nail depths. In contrast, the comparators did not show antifungal efficacy. Nail filing resulted in larger zones of inhibition for amorolfine compared with those of intact nails. CONCLUSIONS: Unlike its comparators, a single application of amorolfine 5% nail lacquer resulted in antifungal efficacy within the nail plate. Nail filing increased the antifungal efficacy of amorolfine 5% nail lacquer.

Efficacy and tolerability of amorolfine 5% nail lacquer in combination with systemic antifungal agents for onychomycosis: A meta-analysis and systematic review.

The efficacy and safety of amorolfine 5% nail lacquer in combination with systemic antifungal agents in the treatment of the onychomycosis were evaluated. According to our meta-analysis, combination treatment of amorolfine 5% nail lacquer and systemic antifungals can result in higher percentage of complete clearance of onychomycosis. It showed that the experimental combination group was more effective than monotherapy of the systemic antifungals [OR (odds ratio) = 1.97, 95%CI (95% confidence interval) = 1.44-2.69], and no more adverse events happened with the addition of amorolfine 5% nail lacquer (OR = .96, 95%CI = .56-1.63, p = .95). This effect strengthens the fact that amorolfine 5% nail lacquer in combination with systemic antifungal agents was better than the monotherapy of systemic antifungals like itraconazole and terbinafine.

Production of Trichophyton rubrum microspores in large quantities and its application to evaluate amorolfine/azole compound interactions in vitro.

Trichophyton rubrum is the most frequently isolated dermatophyte species in European countries. The lack or poor sporulation of T. rubrum has always been a major complication and a limiting factor when performing antifungal susceptibility testing. Therefore, we describe an in vitro method aiming to enhance sporulation of various T. rubrum isolates in order to perform antifungigrams. A combination of high CO2 tensions and incubation on PDA growth medium revealed to be optimal for sporulation of all tested T. rubrum isolates. This method was further used to examine in vitro the combined effects of amorolfine and azole derivatives against fungal growth using adapted checkerboard microdilution assays and an isobolographic approach of the data, adapted disc diffusion and Etest assays. Non-antagonistic and synergistic effects were observed in these settings with amorolfine combined to each of the tested azole compounds. The optimised culture method appeared to be suitable for T. rubrum isolates for which antifungigrams were especially difficult to obtain because of the lack of sporulation.

Patient-reported outcomes from two randomised studies comparing once-weekly application of amorolfine 5% nail lacquer to other methods of topical treatment in distal and lateral subungual onychomycosis.

Patient adherence is a key consideration in the choice of a topical regimen for the treatment of onychomycosis. The objective of this study was to investigate patient-reported outcomes (treatment utilisation, adherence and satisfaction) in onychomycosis treated with once-weekly amorolfine 5% nail lacquer versus once-daily ciclopirox 8% nail lacquer (Study A) or once-daily urea 40% ointment/bifonazole 1% cream combination regimen (Study B). Study A: Subjects received amorolfine and ciclopirox on opposite feet for 12 weeks. Study B: Subjects received amorolfine and urea/bifonazole on opposite feet for 6-7 weeks. Assessments included subject adherence as per label, treatment preference and questionnaire. Study A: More subjects adhered to amorolfine (85%) than to ciclopirox (60%) (P = .025). Overall, subjects were satisfied (95% vs 100%, respectively) and the treatments were balanced in terms of preference (50% vs 45%) at week 12. Study B: More subjects adhered to amorolfine dosage (81.8%) than to the dosage of the urea/bifonazole combination regimen (59.1%) (P = .096). At the end of study, 85.7% of subjects preferred amorolfine versus 14.3% for urea/bifonazole. Fewer subjects experienced local side effects with amorolfine (4.5%) compared to urea (27.3%) and bifonazole (15%). Amorolfine 5% nail lacquer offers a simple and convenient treatment option, which may result in improved patient adherence and consequently lead to improved efficacy and patient satisfaction.

Short Cationic Antimicrobial Peptides Display Superior Antifungal Activities toward Candidiasis and Onychomycosis in Comparison with Terbinafine and Amorolfine.

Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.

Application of cosmetic nail varnish does not affect the antifungal efficacy of amorolfine 5% nail lacquer in the treatment of distal subungual toenail onychomycosis: results of a randomised active-controlled study and in vitro assays.

As onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer (NL) was affected by a masking, natural-coloured, cosmetic nail varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild-to-moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12-week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL-alone group (n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group (n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails.

Combination therapy for onychomycosis using a fractional 2940-nm Er:YAG laser and 5 % amorolfine lacquer.

Onychomycosis remains difficult to cure by traditional methods. The aim of this study was to evaluate the efficacy of combination therapy with a fractional erbium yttrium aluminum garnet (Er:YAG) laser and 5 % amorolfine lacquer on onychomycosis. Nine patients with bilateral nails affected by distal and lateral subungual onychomycosis were included. The bilateral nails of each patient were divided into two groups. The 20 affected nails on one side of each patient as group 1 were treated with a fractional Er:YAG laser once a week and 5 % amorolfine lacquer twice weekly, while the 20 nails on the symmetrical side of each patient as group 2 were treated with amorolfine lacquer only. The laser treatment was conducted at weeks 1, 2, 3, 4, 8, and 12 in group 1. The clinical improvement, onychomycosis severity index (OSI), maximum linear clear nail growth (MLCNG), and mycological cure rate were evaluated. At week 24, 18 of 20 (90 %) nails in group 1 had achieved obvious clinical responses. The mean OSI score showed a significant decrease (5.24) and the average MLCNG was 3.1 mm in group 1. At week 24, 15 of 20 (75 %) nails achieved a negative mycological examination in group 1, compared with four of 20 (20 %) nails in group 2. The treatments were well-tolerated by most patients. This clinical study suggests that combination therapy of a fractional 2940-nm Er:YAG laser and 5 % amorolfine lacquer is an effective, safe, and convenient treatment method for onychomycosis.

Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections.

Although topical antifungal therapies for treating onychomycosis are available, the cure rate is unsatisfactorily low with a simultaneously high risk of recurrence. One reason might be the formation of dormant fungal cells by the pathogen, known as spores, which can survive in the affected nail keratin, thereby evading the effect of antifungal drugs. In this in vitro study, the ability of amorolfine and four other antimycotics (ciclopirox, bifonazole, terbinafine and fluconazole) to kill microconidia of the dermatophyte Trichophyton rubrum, chlamydospores of the dermatophyte Epidermophyton floccosum and blastospores of the yeast Candida albicans was extensively studied as these fungi occur predominantly in onychomycosis. The effectiveness of all five antimycotics depended on the drug concentration and the incubation time: a concentration of 10-1000 times the minimum inhibitory concentration against growing hyphae cells is needed to exert a sporicidal action. Amorolfine and ciclopirox showed the same sporicidal efficacy and kinetics for all three varieties of spores. Both were more effective than fluconazole and bifonazole against microconidia and chlamydospores as well as slightly more potent against chlamydospores and blastospores than terbinafine after 4 days of incubation and at concentrations of ≥10 µg ml(-1). Finally, sporicidal activity on the tested strains was demonstrated for all five different antimycotics used for onychomycosis treatment.

Comparison of user-friendliness and treatment cost of Loceryl® vs. Ciclopoli®--a patient's perspective.

Topical monotherapy is a valid therapeutic approach in onychomycosis. Due to its lengthy course and its non-reimbursed product status, cost and compliance are important issues and non-pharmacological properties such as over-the-counter price and ease of use should be considered when deciding which product to recommend. We investigated surrogate parameters for patient-friendliness and treatment cost in Germany in a questionnaire-based prospective, comparative, intra-individual, open-label trial of the two common topical antifungal nail lacquers Loceryl(®) (amorolfine 5%) and Ciclopoli(®) (ciclopirox 8%) in eight patients with clinically diagnosed onychomycosis. The 2.5 ml bottle of Loceryl(®) covered a treatment period of 308 days, resulting in treatment costs of €0.10 per day in comparison to the 3.3 ml bottle of Ciclopoli(®), covering 127 days at €0.21 per day, given once-daily application for Ciclopoli(®) and once-weekly application for Loceryl(®) in accordance with regulatory approval. Six out of eight patients favoured the Loceryl(®) treatment regimen. Furthermore, four out of eight patients found Loceryl(®) easier to apply, whereas three preferred Ciclopoli(®). In total, seven out of eight stated a clear preference for Loceryl(®) over Ciclopoli(®). Loceryl(®) therapy is less expensive and less time-consuming. The therapeutic period that can be covered is longer and more patients stated a clear preference for Loceryl(®) in comparison to Ciclopoli(®). The differences are statistically significant, underlining probable clinical relevance.

Amorolfine vs. ciclopirox - lacquers for the treatment of onychomycosis.

Amorolfine 5% and ciclopirox 8% nail lacquers are commonly used in topical treatment of onychomycosis. These formulations may be used alone or in combination with oral antifungal agents. Amorolfine and ciclopirox are valuable therapeutic options, however, their usage in monotherapy should be limited. Proper amorolfine and ciclopirox penetration through the nail plate is provided by transungual drug delivery systems. Although amorolfine and ciclopirox have a different mode of action, they both exhibit a broad antifungal activity. The use of antifungal nail lacquers in combination with oral agents, such as terbinafine and itraconazole, improves efficacy of antifungal therapy.

Efficacy and Safety of Amorolfine Lotion 0.25% w/v Compared to Amorolfine Cream 0.25% w/w in Patients With Superficial Fungal Infections of the Skin: A Multi-center, Randomized, Open-Label, Active-Controlled, Non-inferiority Phase III Clinical Trial.

BACKGROUND: Dermatophytosis, a major cause of superficial fungal infections, requires topical and systemic antifungals. Amorolfine, a morpholine derivative, is a new topical antifungal available in cream and lotion formulations. OBJECTIVE: To evaluate the efficacy and safety of amorolfine lotion 0.25% compared to amorolfine cream 0.25% in patients with dermatophytosis. METHODS: A multi-center randomized, two-arm, active-controlled, parallel, non-inferiority phase III clinical trial involving 284 dermatophytosis patients was conducted, with the test arm using amorolfine lotion and the reference arm using amorolfine cream. The study drugs were applied once daily in the evening for four weeks and patients were followed up for another two weeks. The primary endpoint was clinical cure, while secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Safety and tolerability were assessed. RESULTS: Amongst the enrolled patients, 69.9% and 68.1% of patients had tinea corporis, while 30.1% and 31.9% had tinea cruris. The majority of patients in both groups (99.3% test and 97% reference) achieved a clinical cure at the end of treatment. Mycological cure was achieved by 98.6% and 96.3% respectively. A composite cure was achieved by 98.6% in the test arm versus 96.3% in the reference arm. A total of two AEs were reported in two (1.4%) patients in the test group and three AEs were reported in three (2.1%) patients in the reference group, all of the AEs were mild and resolved within three days without supportive medication. No severe adverse effects were reported in any of the study subjects. CONCLUSION: Amorolfine lotion 0.25% w/v showed a non-inferior clinical, mycological, and composite cure in dermatophytosis patients, was well-tolerated, and had a similar safety profile to amorolfine cream 0.25% w/w.