Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Isavuconazonium Sulfate in Healthy Adult Japanese Subjects

Abstract

Isavuconazonium sulfate is the water-soluble prodrug of the novel, broad-spectrum, triazole antifungal agent isavuconazole. This was a first-in-Japanese study assessing the pharmacokinetics, safety, and tolerability of isavuconazonium sulfate. The study was conducted in 2 parts: part 1 (single ascending dose; 100-, 200-, and 400-mg equivalent of isavuconazole oral or intravenous administration); and part 2 (multiple doses for 16 days; 200-mg equivalent of isavuconazole oral or intravenous administration; once-daily administration with a loading regimen every 8 hours for the first 48 hours). A total of 60 and 16 subjects were randomized in part 1 and part 2, respectively. Observed clearance was lower in this study compared to what was previously reported in predominantly White populations and similar to clearance in non-Japanese Asian populations. The range of the plasma isavuconazole concentration in this study was within the range of the pivotal phase 3 study, with no relationship between isavuconazole exposure and either efficacy or safety. There were no serious adverse events, and all reported treatment-emergent adverse events were of mild intensity. This study confirmed that isavuconazonium sulfate was safe and well tolerated in healthy adult Japanese subjects.