Source: Health Products Regulatory Authority (IE) Revision Year: 2018 Publisher: Polichem S.A., 50, Val Fleuri, L-1526 Luxembourg, Luxembourg
Pharmacotherapeutic group: Antifungals for dermatological use; Other antifungals for topical use
ATC code: D01AE14
Onytec nail lacquer is an original, patented formulation of ciclopirox based on hydroxypropyl chitosan for delivery of the active ingredient to nails.
Onytec nail lacquer has a topic, anti-mycotic action. The active ingredient is ciclopirox (pyridone derivative). In vitro, ciclopirox has been shown to be both fungicidal and fungistatic as well as having sporicidal activity. Ciclopirox has activity against a broad spectrum of dermatophytes, yeasts, moulds and other fungi. For most dermatophytes (Trichophyton species, Microsporum species, Epidermophyton species) and yeasts (Candida albicans, other Candida species) the MIC falls within the range of 0.9 to 3.9 μg/ml.
Table of susceptibility (strains relevant to illness):
| Dermatophytes | Trichophyton rubrum Trichophyton mentagrophytes Trichophyton spp Microsporum canis Epidermophyton floccosum |
| Yeasts | Candida albicans Candida parapsilosis |
| Moulds | Scopulariopsis brevicaulis Aspergillus spp Fusarium solani |
Onytec nail lacquer has been investigated in a long term clinical study in 467 patients with onychomycosis, compared to placebo and a commercially available formulation of ciclopirox 8% nail lacquer. All treatments were applied every day for 48 weeks to the infected nails. The patients were followed up for a further period of 12 weeks. All the efficacy assessments were done on a target great toenail.
Table of the results at the end of follow-up (week 60):
| End-point | Onytec nail lacquer | Placebo | EU Reference product |
|---|---|---|---|
| complete "cure"* | 12.7% | 1.3% | 5.8% |
| "responders"# | 28.7% | 14.7% | 17.3% |
| "improvement"§ | 46.5% | 34.7% | 39.7% |
| Decrease of diseased nail¥ | 36.3% | 16.2% | 21.8% |
* Conversion to negative of both KOH microscopy and fungal culture, and 100% healthy appearing target great toenail.
# Conversion to negative of both KOH microscopy and fungal culture, and decrease of diseased nail area to ≤10% (including zero) of total as assessed by the blinded Evaluator.
§ Patients with at least 20% decrease of diseased nail area, as assessed by the blinded Evaluator, at the end of treatment versus baseline and conversion to negative KOH and culture.
¥ Decrease of diseased nail area to ≤10% of total as assessed by the blinded Evaluator.
Onytec nail lacquer showed a better efficacy compared to placebo and to reference ciclopirox. A better effect was evidenced on the primary endpoint “cure” rate and on the key secondary endpoint “responder” rate, being 119% higher than the reference for cure rate (statistically significant, p<0.05) and 66% higher for responder rate (statistically significant, p<0.05). In the clinical study no drug-related systemic adverse event was recorded.
Tolerability at the application site was continuously monitored throughout the treatment period. Signs and symptoms recorded were 2.8% and 7.8%, respectively, in the Onytec group; 8.6% signs and 16% symptoms were recorded in the reference group and 7.2% signs and 12.4% symptoms were recorded in placebo group. The most frequent sign recorded was erythema (2.8% in the Onytec group and 8.6% in the reference group). The most frequent symptom was burning (2.8% in the Onytec group and 10.7% in the reference group).
A further second randomized long-term clinical study was conducted on 137 onychomycotic patients. It was a randomized, two arms, 48-week study, comparing Onytec nail lacquer daily applied with a marketed formulation of 5% amorolfine nail lacquer on acrylate basis given twice a week.
All the efficacy variables (study endpoints) were evaluated on a target great toenail.
The study has attained its primary objective, i.e. Onytec nail lacquer, after 12 weeks of treatment, was not inferior to amorolfine 5% in the culture conversion to negative: conversion to negative of culture 78.3% for Onytec nail lacquer vs. 64.7% amorolfine 5% nail lacquer, meaning a difference of 13.6% between the treatments (95% confidence interval [-1.4; 28.5]).
At weeks 48 the percentages of patients with complete cure rate, treatment success/responder rate and mycological cure in the Onytec group, were consistently higher than in the reference group:
Table: results at the end of treatment (week 48):
| End-points | Onytec nail lacquer | 5% amorolfine nail lacquer | Difference (%) | 95% confidence interval for the difference |
|---|---|---|---|---|
| Complete cure rate* | 35.0% | 11.7% | 23.3** | 8.8; 37.9 |
| Treatment success# | 58.3% | 26.7% | 31.7** | 14.9; 48.4 |
| Mycological cure$ | 100% | 81.7% | 18.3** | 8.5; 28.1 |
* conversion to negative of both KOH microscopy and fungal culture, and 100% healthy target great toenail, as assessed by the blinded evaluator
# conversion to negative of both KOH microscopy and fungal culture, and decrease of diseased nail area to ≤10% of total as assessed by the blinded evaluator
$ conversion to negative of both KOH microscopy and fungal culture
** p<0.001
In this clinical study, too, no drug-related systemic adverse event was recorded.
Onytec nail lacquer was well tolerated in terms of local and general adverse reactions. Signs of irritation were only found in 2.06% of the Onytec nail lacquer group at the skin surrounding the treated nails.
Onytec nail lacquer has demonstrated good penetration properties through keratin. By achieving fungicidal concentrations at the site of infection, the active substance leads to irreversible binding to the fungal cell wall and this causes inhibition of the uptake of components needed for cellular synthesis and of the respiratory chain.
A very small amount of ciclopirox is absorbed systemically (<2% of the applied dose and the blood levels in a long term study were 0.904 ng/ml (n=163) and 1.144 ng/ml (n=149) after 6 and 12 months of treatment, respectively. This shows that the drug exerts its activity particularly at the local level and the risk of possible interference with the normal body functions is negligible.
Preclinical data up to a daily oral dose of 10 mg ciclopirox/kg revealed no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenic potential. In reproduction studies in rats and rabbits no embryo-/fetotoxicity or teratogenicity was found. At the oral dose of 5 mg/kg, a reduced fertility index in the rat was observed. There was no evidence for peri- or postnatal toxicity, however possible long term effects on progeny have not been investigated. Onytec nail lacquer exhibited no irritation in studies on local tolerance in rabbits and guinea pigs.
The chitosan derivative contained in the formulation is free of tropomiosine and did not exhibit allergenic potential in patients with shellfish allergy.
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