Study to Evaluate the Efficacy and Safety of P-3058 Nail Solution in the Treatment of Onychomycosis

Study Overview
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Brief Summary
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The aim of this phase III study is to establish the efficacy and safety of P-3058 (terbinafine 10% nail solution) topically administered once weekly in patients with onychomycosis in comparison to the Vehicle in a double-blind fashion. The overall treatment period will be of 48 weeks.

Detailed Description
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The study will consist of a screening phase, a treatment phase of 48 weeks and a 12-week follow-up. Patients affected by mild to-moderate distal lateral subungual onychomycosis (DLSO) on a target great toenail will be included in the study. Clinical as well as mycology assessments will be performed throughout the whole study. Safety will be monitored by recording any adverse event and evaluating local tolerability.

Official Title
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A Multicenter, Randomized, Double-blind, Parallel, Vehicle-controlled Study to Evaluate the Efficacy and Safety of P-3058 10% Nail Solution in the Treatment of Onychomycosis

Conditions
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Onychomycosis of Toenail

Intervention / Treatment
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* Drug: P-3058 (terbinafine hydrochloride 10%)
* Drug: Vehicle of P-3058


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent before starting any study related procedures. Patients aged 12 and older of any race. Males or females. Outpatients. Clinically diagnosed mild-to-moderate distal lateral subungual onychomycosis (DLSO) of at least one great toenail (the target nail) at the Screening visit (V1). Patients with onychomycosis involving ≥ 20% to ≤ 50% of the area of the target great toenail. Patients with a positive KOH examination. Patients with positive culture for dermatophyte(s). Evidence of target great toenail growth reported by the patient defined as at least monthly nail clipping. Exclusion Criteria: Woman who is pregnant, nursing an infant, or planning a pregnancy during the study period. Patients with history of allergic reactions to terbinafine or its excipients. Use of any investigational drug/device or participation in a previous clinical trial within four weeks prior to Screening visit (V1). Patients using nail polish or other nail cosmetic product on the concerned nails from at least 24 hours prior to Screening visit (V1) until the end of the study. Use of systemic antifungal drugs in the 24 weeks prior to Screening visit (V1) or non-responsive to systemic antifungal therapy for onychomycosis. Nail application of topical antifungal drugs or device in the 4 weeks prior to Screening visit (V1). Presence of any nail infections other than dermatophyte. Presence of onychodystrophy that could interfere with clinical assessments. Presence of yellow spikes on the target nail. Presence of dermatophytoma on the target nail. Presence of nail thickness exceeding 2 mm. Patients with proximal subungual involvement (marker of immunosuppressed patient). Patients with severe plantar or moccasin tinea pedis (defined by blistering, pustules or inability to ambulate). Patients with nail abnormalities due to conditions like psoriasis, lichen planus, immune dysfunction, collagen-vascular diseases, peripheral vascular disease. Patients with life expectancy less than 2 years. Chemotherapy, immunosuppressive therapy in the 12 weeks prior to Screening visit (V1). Systemic corticosteroids, antimetabolites and immune-stimulants therapy in the 4 weeks prior to Screening visit (V1). HIV infection or any other immunodeficiency. Alcohol or substance abuse. Patients/parents (or legal guardian) unable to understand the procedures and purposes of the study. Any other condition that, in the opinion of the Investigator, would prevent the subject from effectively participating in the study, place the subject at risk or effect the assessment of efficacy and safety of the study medication.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Vehicle-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-3058<br> | Drug: P-3058 (terbinafine hydrochloride 10%)<br>* Patients will apply the P-3058 nail solution once weekly in a double blind fashion. The overall treatment phase is of 48 weeks.<br>|
| Placebo Comparator: Vehicle<br> | Drug: Vehicle of P-3058<br>* Patients will apply the Vehicle of P-3058 once weekly in a double blind fashion. The overall treatment phase is of 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete cure at Week 60 | Defined as composite of negative KOH microscopy and negative culture for dermatophytes and no residual clinical involvement (nail totally clear) of the target nail. | Baseline - Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate at Week 60 | Defined as negative Potassium Hydroxide (KOH) microscopy and negative culture for dermatophytes and ≤ 10% residual involvement of the target toenail) | Baseline - Week 60 | 
| Mycological cure rate at Week 60 | Defined as negative Potassium Hydroxide (KOH) microscopy and negative culture for dermatophytes of the target nail. | Baseline - Week 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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terbinafine nail solution, nail fungal infection, topical antifungal drug