Efficacy, Safety, and Tolerability of Topical Terbinafine in Patients With Mild to Moderate Toenail Fungus of the Big Toenail

Study Overview
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Brief Summary
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This study is designed to assess the efficacy, safety and tolerability of a topical formulation of terbinafine solution applied daily in patients with toenail fungus. This trial will study patients with mild to moderate toenail fungus disease of the big toenail and their responses to two treatment durations, 24 or 48 weeks.

Official Title
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A Randomized, Double-blind, Vehicle-controlled, Multicenter, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of Topical Terbinafine Hydrogen Chloride (HCl) Formulation for 24 or 48 Weeks of Treatment in Patients With Mild to Moderate Toenail Onychomycosis

Conditions
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Onychomycosis

Intervention / Treatment
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* Drug: terbinafine
* Drug: Placebo
* Drug: terbinafine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and females 12 - 75 years of age Fungal toenail infection of one or both of the large (great) toenails The nail infection must be due to a dermatophyte, (mixed infections [dermatophyte and non-dermatophyte] are not allowed) Exclusion Criteria: Target foot must not have severe plantar (moccasin) tinea pedis that would require systemic therapy. Mild to moderate tinea pedis (athlete's foot) infection should be treated with terbinifine prior to baseline or at any time during the trial. Other topical treatments for athlete's foot may be recommended at the discretion of the investigator. Subjects must not have abnormalities of the nail that could prevent a normal appearing nail if clearing of infection is achieved No administration of systemic antifungal medications within 6 months prior to screening visit No application of prescription topical antifungal medications for toenail fungus within 3 months or other commercially available topical medications for toenail fungus applied directly to the toenails within 1 month prior to screening visit No professional pedicures or application of any nail polish product or nail cosmetic to the toenails after the screening visit Known pregnancy or lactation at time of enrollment Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 12 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 48 weeks | Drug: terbinafine<br>* Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) once daily for 48 weeks<br>* Other names: Lamisil;|
| Placebo Comparator: 2<br>vehicle (placebo) applied once daily for 48 weeks | Drug: Placebo<br>* vehicle (placebo) applied once daily for 48 weeks<br>|
| Experimental: 3<br>Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) applied once daily for 24 weeks | Drug: terbinafine<br>* Active terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) once daily for 24 weeks<br>* Other names: Lamisil;|
| Placebo Comparator: 4<br>vehicle (placebo) applied once daily for 24 weeks | Drug: Placebo<br>* vehicle (placebo) applied once daily for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Assessed by Complete Cure Rate at the End of Study (Week 52) After Treating for 24 or 48 Weeks. | Complete cure is defined as negative KOH microscopy and negative culture for dermatophytes. and no residual involvement of the target toenail. The complete cure was a composite binary variable defined as Yes if: Mycological cure (negative KOH and negative culture for dermatophytes) and No residual involvement of the target toenail No if otherwise | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Assessed by Mycological Cure (Negative Culture and Negative KOH Microscopy) at the End of Study After Treating Patients for 24 or 48 Weeks. | Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes. Mycological cure was a composite binary variable defined as Yesif : Negative microscopy and Negative culture for dermatophytes No if otherwise. | 52 weeks | 
| Efficacy Assessed by Clinical Efficacy at the End of Study After Treating Patients for 24 or 48 Weeks. | Clinical effectiveness is defined as negative KOH microscopy and negative culture for dermatophytes and <= 10% residual involvement of the target toenail. Clinical effectiveness was a composite binary variable defined as Yes if Mycological cure (negative KOH and negative culture for dermatophytes) and = 10% residual involvement of the target toenail No if otherwise | 52 weeks | 
| Number of Participants Assessed With Adverse Events and Serious Adverse Events | An adverse event (AE) is any adverse change in health or side effect that occurs while the participant is receiving the treatment or within a previously specified period of time after the treatment has been completed. A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening requires, inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toenail fungus, Onychomycosis, Nail fungus, Toenail fungal infection, Tinea unguium, Dermatophytes, Foot dermatoses