Ciclopirox Hydroxypropyl Chitosan: Efficacy in Mild-to-Moderate Onychomycosis.

The severity and percentage of nail involvement are usually considered the main prognostic factors for the treatment of onychomycosis. This study investigated the efficacy of P-3051 (ciclopirox [CPX] 8% nail lacquer in hydroxypropyl chitosan technology) in a population subset of the pivotal study, selected according to the criteria used in recent onychomycosis pivotal studies. The original study was a multicenter, randomized, three-arm, placebo-controlled, parallel groups, evaluator-blinded study comparing P-3051 with reference CPX (standard, insoluble 8% CPX nail lacquer) and placebo (P-3051 vehicle) in a 2: 2: 1 ratio, applied once daily for 48 weeks to 467 patients with onychomycosis, followed by a 12-week follow up. The primary endpoint was complete cure (negative mycology and 100% clear nail) at the end of treatment. Among the secondary endpoints, response rate (negative mycology and ≥90% clear nail) and negative culture were chosen as most representative for a clinical setting. A population subset (modified intention-to-treat population, 302 patients) was selected, excluding those with more severe disease (> 50% nail involvement), in line with recent onychomycosis pivotal trials. P-3051 was superior to placebo in all parameters but culture at week 60 and was superior to reference CPX in cure and response rates at week 60. Compared to the overall patient population, efficacy rates in the P-3051 group were higher in the subset excluding patients with nail involvement > 50%. Results increased by 33% (from 5.7 to 7.6%) at week 48 and by 19.0% (from 12.7 to 15.1%) at week 60 for cure rate, by 33% (from 24.0 to 31.9%) and 20% (from 28.7 to 34.5%) for response rate, and by 3% (from 89.1 to 91.6%) and 4.0% (from 79.0 to 82.4%) for culture conversion to negative. This post hoc analysis confirms that the severity of onychomycosis is a prognostic factor for responsiveness to antifungal treatments and that this can significantly affect reported efficacy data. The different inclusion criteria should be taken into account when reviewing the efficacy of antifungal agents from different studies.