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

• Published in: Journal of dermatology Vol. 45; no. 10; pp. 1151 - 1159
• Main Authors: Watanabe, Shinichi, Tsubouchi, Ichiro, Okubo, Akihiro
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2018; John Wiley and Sons Inc
• Subjects: Adult; Aged; Antifungal activity; Antifungal agents; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; Clinical trials; Double-Blind Method; Double-blind studies; Female; Foot Dermatoses - drug therapy; fosravuconazole; Fungal infections; Humans; Lysine; Male; Middle Aged; Onychomycosis; Onychomycosis - drug therapy; oral antifungal agents; Original; Patients; Potassium hydroxide; Prodrugs - therapeutic use; randomized controlled trial; Ravuconazole; Safety; Thiazoles - therapeutic use; Toenail; Treatment Outcome; Triazoles - adverse effects; Triazoles - therapeutic use; Young Adult; fosravuconazole; onychomycosis; ravuconazole; oral antifungal agents; randomized controlled trial
• ISSN: 0385-2407; 1346-8138; 1346-8138
• DOI: 10.1111/1346-8138.14607

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.