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

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

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).

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.

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).

To characterize plasma concentrations of terbinafine and metabolite from a subset of patients over the study period

To characterize nail concentrations of terbinafine and metabolite from patients over the study period

To evaluate the ease and durability of once monthly and once bi-monthly HSG subungual topical treatments to the target toe over 44 weeks. Nail measurements indicating progressive clearing are recorded from an Investigator Global Assessment scale referencing % disease involvement corroborated by nail image analysis. The ease and durability of subungual topical treatment is established using a 5-point Likert Scale. Patient local tolerability is established using a Treatment Site Assessment Scale and Pain Intensity Scale.

To establish each patient's impression of DLSO improvement in their target toe over the study period, patients will reference the following scale (0 = clear of DLSO, 1 = marked improvement of DLSO, 2 = moderately improved DLSO, 3 = slightly improved DLSO, 4 = unchanged, 5 = worse)

Indicated by the number of patients with treatment-related adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE)

Indicated by clinically significant changes in patient liver function, serum chemistry, urinalysis, and complete blood count over the study period

Monitored by assessing clinically significant changes in patient medical condition and/or use of medications over the study period

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