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.

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