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 <scp>III</scp> study

<jats:title>Abstract</jats:title><jats:p>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‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content>, 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 (<jats:italic>n</jats:italic> = 153) were randomly assigned to receive F‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content> (100 mg <jats:styled-content style="fixed-case">RVCZ</jats:styled-content>,<jats:italic> n</jats:italic> = 101) or placebo (<jats:italic>n</jats:italic> = 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‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content>. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content> (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (<jats:italic>P</jats:italic> < 0.001). The mycological cure rate at week 48 was also significantly higher with F‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content> (82.0%, 73/89) than the placebo (20.0%, 10/50, <jats:italic>P</jats:italic> < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (<jats:styled-content style="fixed-case">ADR</jats:styled-content>) in 23.8% (24/101) and 3.8% (2/52) of F‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content> and placebo subjects, respectively. <jats:styled-content style="fixed-case">ADR</jats:styled-content> were mild to moderate in severity, with none being serious. F‐<jats:styled-content style="fixed-case">RVCZ</jats:styled-content> (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.</jats:p>