To Evaluate Hallux Terbinafine Subungual Gel (HSG) in the Treatment of Onychomycosis

Study Overview
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Brief Summary
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The key objective is to establish the efficacy, safety, tolerability, and pharmacokinetics of investigational drug Hallux Terbinafine Subungual Gel (HSG) administered over 44 weeks to patients with distal-lateral subungual onychomycosis (DLSO).

Detailed Description
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Primary Efficacy: To identify patients achieving Complete Cure in the target toenail at Week 52. Secondary Efficacy: To identify patients that have achieved 1) Clinical Cure, 2) Mycological Cure, and/or 3) Positive Response in the target toenail at Week 52. Plasma Pharmacokinetics: To characterize concentrations of terbinafine and major metabolite in a subpopulation of patients over the study period. Nail Pharmacokinetics: To characterize concentrations of terbinafine and major metabolite in distal nail clippings in patients over the study period. HSG Safety and Tolerability Profile: To establish from plasma pharmacokinetics, related adverse events, treatment site reactions, pain, clinically significant changes in medical condition and/or medications, and clinically significant changes in liver function, serum chemistry, urinalysis, and complete blood count over the study period. Subungual Topical Procedure: To establish the ease and durability of once monthly and once bi-monthly HSG subungual topical treatments, the Investigator will record at selected time points 1) nail measurements indicating progressive clearing, 2) the ease and depth of each topical administration, 3) the investigational drug volume administered each treatment, and 4) patient tolerability.

Official Title
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An Open Label Phase 2a Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Hallux Terbinafine Subungual Gel Administered to the Toenail Bed of Patients With Distal-Lateral Subungual Onychomycosis

Conditions
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Onychomycosis of Toenail

Intervention / Treatment
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* Drug: Hallux Terbinafine Subungual Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and females 18 - 75 years of age inclusive Patients with DLSO of at least one great toe Patients with DLSO in the target toe confirmed by positive KOH and positive fungal culture for dermatophytes Willingness to abstain from pedicures, nail clipping, or application of nail polish or nail cosmetics to their toenails over the study period Exclusion Criteria: History of any significant chronic fungal disease other than onychomycosis or an immunocompromised condition Any previous surgery to or abnormalities of the target toe that in the investigator's opinion could prevent the toenail surface area from clearing even if eradication of the DLSO infection is achieved Participation in another clinical study of an investigational drug or device within 3 months of screening No administration of oral terbinafine or another oral antifungal within 6 months of screening No topical antifungal used for onychomycosis or a dermatophyte infection (i.e. tinea pedis) within 3 months of screening No uncontrolled diabetes mellitus No severe psoriasis or severe atopic dermatitis Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSG<br>Hallux terbinafine subungual gel | Drug: Hallux Terbinafine Subungual Gel<br>* Hallux Terbinafine Subungual Gel (HSG) administered every 1 to 2 months over 44 weeks.<br>* Other names: HSG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Cure at Week 52 in the Target Toe | Complete Cure is defined as 1) 100% healthy, clear nail, and 2) negative mycology. Healthy, clear nail is absent any disease involvement attributable to DLSO and is determined by Investigator Global Assessment (IGA). Negative mycology is defined as zero visualization of septate hyphae by KOH microscopy (negative KOH) combined with a fungal culture negative for causal dermatophytes (negative fungal culture). | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure in the Target Toe | 100% healthy, clear nail | Week 52 | 
| Mycological Cure in the Target Toe | Negative KOH, negative fungal culture | Week 52 | 
| Positive Response in the Target Toe | ≥ 80% decrease in disease involvement | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Onychomycosis