A phase II, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onychomycosis

Abstract

Background: Onychomycosis is effectively treated with terbinafine and itraconazole. However, frequent repeated dosing is required, and hepatic and cardiac adverse events may occur.

Objectives: Evaluate efficacy and safety of albaconazole, a novel triazole, for once-weekly treatment of distal subungual onychomycosis of the great toenail.

Methods: This double-blind, phase II study randomized 584 patients to receive albaconazole 100 to 400 mg or placebo weekly for 24 or 36 weeks. Effective treatment was measured as mycologic cure and clear or almost clear nail at week 52.

Results: All treatment groups achieved greater effective treatment rates (21%-54%) compared to placebo (1%; P < .001 for all groups) at week 52. Effective treatment was attained at week 24 in ≥5% of patients in most groups. Most adverse events were mild or moderate, and treatment-related adverse events were all ≤3%. No treatment-related hepatic or cardiac serious adverse events were observed.

Limitations: The follow-up period was likely too short to detect maximal efficacy; cure rates were increasing at study end. The efficacy and tolerability of albaconazole were not compared with other available treatments, and the global change in target toenail scale was subjective.

Conclusions: Albaconazole was well tolerated at all doses and resulted in high cure rates for onychomycosis.

Keywords: AE; ECG; ITT; KOH; PK; PP; SAE; SD; TEAE; adverse event; albaconazole; dermatophyte; electrocardiogram; intent to treat; nail fungus; onychomycosis; per protocol; pharmacokinetic; phase II study; potassium hydroxide; serious adverse event; standard deviation; treatment-emergent adverse event; triazole.