Evaluation of Ciclopirox in the Clinical Progression of Onychomycosis: A Phase IV, Multicenter, Single-Arm Study

The primary objective of this Phase IV, multicenter, single-arm clinical trial is to evaluate the **clinical evolution** in patients with **onychomycosis** treated with DexULac® over a period of 48 weeks. This objective is clinically relevant as it aims to assess the effectiveness of the treatment in managing the severity of nail fungal infections, which can significantly impact patient quality of life and nail health.

Secondary objectives include:

• Evaluating the evolution of quality of life in patients with onychomycosis treated with DexULac® during 48 weeks of treatment.
• Assessing the clinical success in patients with onychomycosis treated with DexULac® over a period of 48 weeks.
• Evaluating the clinical improvement in patients with onychomycosis treated with DexULac® over a period of 48 weeks.
• Determining the time required to achieve clinical success in patients with onychomycosis treated with DexULac® over a period of 48 weeks.
• Evaluating the mycological cure using Polymerase Chain Reaction (PCR) in patients with onychomycosis treated with DexULac® during a period of 48 weeks.
• Assessing the evolution of the patient's perception regarding nail alterations during the 48 weeks of treatment with DexULac®.
• Evaluating the safety profile of treatment with DexULac® for 48 weeks.

The clinical trial involves participants diagnosed with **onychomycosis**, specifically mild to moderate distal onychomycosis due to dermatophyte fungi, with nail involvement between 10% and 40%. The study population includes adult men and women aged between 18 and 75 years. Participants must have been diagnosed with onychomycosis within the last six months. Both male and female subjects are included, and the trial does not involve a vulnerable population. Women of childbearing potential are required to have a negative urine pregnancy test and must agree to use effective contraception from 14 days before the first administration until 4 weeks after the last administration of the investigational medication. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase IV**, multicenter, single-arm study designed to evaluate the effect of DexULac, a **medicated nail lacquer** containing **ciclopirox**, on the evolution of the severity of **onychomycosis** and the quality of life in patients. The trial aims to assess the clinical evolution in patients with onychomycosis treated with DexULac over a period of 48 weeks. The study will involve adult men and women aged 18 to 75 years who have been diagnosed with mild to moderate distal onychomycosis due to dermatophyte fungi, with nail involvement between 10% and 40% at the time of inclusion. The trial will exclude any participants who do not meet these criteria.

The trial will commence with a screening visit to confirm eligibility, during which informed consent will be obtained, and baseline assessments will be conducted. The primary endpoint will be the mean change in the Onychomycosis Severity Index (OSI) from baseline to 12, 24, 36, 48, and 52 weeks. Secondary endpoints include the evaluation of the quality of life through the Dermatology Life Quality Index (DLQI) and the assessment of clinical success and improvement based on the reduction in the affected nail area. The safety profile of DexULac will be monitored by recording adverse events throughout the study duration.

Participants will attend regular follow-up visits at 12, 24, 36, 48, and 52 weeks to monitor progress and assess both primary and secondary endpoints. The end-of-study visit will occur at 52 weeks or within 4 weeks after the last treatment visit if clinical success is achieved earlier. The expected length of participant involvement is up to 52 weeks, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or the occurrence of adverse events that necessitate discontinuation. The trial is estimated to conclude by May 31, 2027, with recruitment starting on April 30, 2025.

The clinical trial involves the use of **DexULac** 80 mg/g, a **medicated nail lacquer** specifically formulated for the treatment of **onychomycosis**. The active ingredient in this formulation is **ciclopirox**, a chemical substance known for its antifungal properties. The lacquer is applied topically to the affected nails. The recommended dosage is a maximum of 80 mg/g per day, with the treatment period extending up to 48 weeks. The lacquer is manufactured by Laboratorio Reig Jofre, S.A., and is not a pediatric formulation. The application of the lacquer is intended to be consistent and regular, ensuring optimal therapeutic outcomes.

In this single-arm clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the efficacy and safety of **DexULac** in improving the severity of onychomycosis and enhancing the quality of life in patients. Participant compliance with the treatment regimen is monitored throughout the study to ensure adherence to the dosing schedule and to assess the clinical evolution of the condition over the 48-week period.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves evaluating the clinical evolution of **onychomycosis** by measuring the mean change in the Onychomycosis Severity Index (OSI) from baseline to weeks 12, 24, 36, 48, and 52. Secondary endpoints include assessing the evolution of patients' quality of life using the Dermatology Life Quality Index (DLQI), with measurements taken from baseline to weeks 12, 36, 48, and 52. The DLQI will be conducted at all study visits until clinical success is achieved or after the follow-up period, which concludes within four weeks post-treatment, with a maximum duration of 52 weeks.

Additional secondary endpoints include evaluating clinical success based on the percentage of patients with a reduction in the diseased nail area to less than 10% of the total area of the first toe, assessed through photographic images at weeks 12, 24, 36, 48, and 52. Clinical improvement is similarly evaluated by the percentage of patients showing at least a 20% decrease in the affected nail area. The time required to achieve clinical success, defined as a reduction in the diseased nail area to less than 10%, will also be measured. Mycological cure will be assessed by the negativization rate of the PCR test within four weeks after the end of treatment, analyzing the presence of dermatophyte fungi. The patient's perception of nail alterations will be evaluated through a subjective questionnaire at weeks 12, 36, 48, and 52. The safety profile of DexULac® treatment will be monitored by recording the total number and frequency of Adverse Events (AEs), serious AEs (SAEs), and Adverse Reactions (ARs) from baseline to 48 weeks, including the severity and causality of each event.