Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study.

Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F-RVCZ, compared with a placebo, were investigated in a multicenter, double-blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F-RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end-point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36-week post-treatment visit). Secondary end-points were changes over time in the efficacy and mycological effect of F-RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F-RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F-RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F-RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F-RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.