Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis,☆☆,,★★,

https://doi.org/10.1067/mjd.2000.109071Get rights and content

Abstract

Background: Onychomycosis is a relatively common condition affecting toenails more than fingernails. It is caused predominantly by dermatophytes. Onychomycosis can cause pain and discomfort and has the potential to be a source of morbidity. Objective: We evaluated the efficacy and safety of ciclopirox nail lacquer solution 8% used to treat onychomycosis of the toe in the United States and in centers worldwide. Methods: Two identically designed, double-blind, vehicle controlled, parallel group multicenter studies were performed in the United States to evaluate the use of ciclopirox nail lacquer to treat mild to moderate toe onychomycosis caused by dermatophytes. In the first study, 223 patients were randomized to treatment (ciclopirox group: 112, vehicle group: 111), and in the second study, 237 subjects were randomized (ciclopirox group: 119, vehicle group: 118). Before randomization, patients were to have clinical features of onychomycosis in at least one great toe with positive light microscopic examination and a positive dermatophyte culture. The test material was applied daily for a period of 48 weeks to all toenails and affected fingernails, covering the entire nail plate and approximately 5 mm of surrounding skin. At baseline, subjects had between 20% to 65% area of target nail involved. Physician's assessments were carried out every 4 weeks, and mycologic evaluation and photographic planimetry using standardized photographs were performed every 12 weeks during the 48 weeks of treatment. In studies conducted outside the United States, patients were also to have clinical, microscopic, and culture evidence of onychomycosis. However, these studies included some patients infected with nondermatophyte organisms (eg, Candida species), and the area of nail involvement was generally greater than observed in the US studies. Treatment regimens also varied in the non-US studies with lacquer applications that were sometimes less frequent than the once daily treatment used in the US studies (eg, alternate day or twice weekly). In addition, the typical duration of treatment was 6 months in the non-US studies as compared with 48 weeks in the United States. Outcome measures were similar to those used in the US trials, although a non-photographic planimetric method was used to quantify disease extent. Results: Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer 8% topical solution is significantly more effective than placebo in the treatment of onychomycosis caused by Trichophyton rubrum, and of mild to moderate toe onychomycosis without lunula involvement. At the end of the 48-week treatment period, the mycologic cure rate (negative culture and negative light microscopy) in study I was 29% vs 11% in the ciclopirox and vehicle groups, respectively. Similarly, the mycologic cure rate for study II was 36% vs 9%, respectively. In the non-US studies, the mycologic cure rates ranged from 46.7% to 85.7%. In addition, ciclopirox nail lacquer has demonstrated a broad spectrum of activity with efficacy against Candida species and some nondermatophytes in non-US studies. Ciclopirox nail lacquer is considered extremely safe regarding causally related treatment emergent adverse-effects (TEAEs), with most TEAEs transient and localized to the site of action (eg, erythema and application site reaction). In the US studies, TEAEs were generally mild and cleared while the patient continued to use the nail lacquer. Conclusions: Studies conducted worldwide demonstrate the efficacy of ciclopirox nail lacquer for the treatment of finger and toe onychomycosis. Both controlled and open-label studies confirm the excellent safety profile of this topical therapy. Thus, the nail lacquer provides a treatment choice with a favorable benefit-to-risk ratio. With its novel mechanism of action and its topical route of administration, ciclopirox nail lacquer offers an innovative approach to the treatment of this often difficult-to-manage disease. (J Am Acad Dermatol 2000;43:S70-80.)

Section snippets

Study design

Baseline evaluation included recording information such as demographic data, medical history, duration of onychomycosis, and the presence or absence of chronic tinea pedis. A physical examination was conducted; clinical laboratory and mycologic sampling was carried out, ensuring that the eligibility criteria were met. Each eligible subject was randomly assigned to receive either the active treatment or matching vehicle for 48 weeks. Subjects reported to the clinic for evaluations by the

Study patients

In the first study (Study 312), a total of 223 individuals were randomized to treatment and were included in the ITT analysis (ciclopirox group: 112, vehicle group: 111). Of the patients randomized to treatment, 89 (79.5%) and 84 (75.7%) completed the study for the active and vehicle group, respectively. Similarly, 237 subjects were randomized to treatment in study II (Study 313) and were included in the ITT analysis (ciclopirox: 119 subjects, vehicle: 118). Of the patients randomized to

Non-US trials conducted to determine the efficacy and safety of ciclopirox nail lacquer

Thirteen trials that have been conducted outside of the United States using ciclopirox nail lacquer to treat onychomycosis of fingers and toes are summarized in Table IV.

. Summary of some non-US studies where ciclopirox nail lacquer has been used to treat onychomycosis

Empty CellEmpty CellEmpty CellEmpty CellEmpty CellEmpty CellEfficacy outcomes
Study locationType of studyTreatment regimenToenails/fingernailsCausative organismsAdverse eventsMycologic cureClinical cureClinical response
FinlandRandomized double-blindEvery 2nd day application × 3-6 months.

Discussion

Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer is significantly more effective than placebo (vehicle) in the treatment of mild to moderate toe onychomycosis without lunula involvement, caused by T rubrum. These studies establish the efficacy of the nail lacquer for the treatment of onychomycosis in the great toe, which is usually difficult to treat because of disease extent, high rates of reinfection, and slow nail growth rates. In addition, the efficacy of

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    This article is part of a supplement sponsored by Aventis.

    ☆☆

    Dr Baran and Dr Fleckman have been consultants for Aventis.

    Dr Gupta has been a consultant for Aventis, Janssen, Novartis, and Pfizer.

    ★★

    Reprint requests: Aditya K. Gupta, MD, FRCP(C), 490 Wonderland Road South, Ste 6, London, Ontario Canada N6K 1L6.

    J Am Acad Dermatol 2000;43:S70-80.

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