A Pharmacokinetic Bioequivalence Study Comparing Different-Strength and -Size Capsules of Isavuconazonium Sulfate in Healthy Japanese Subjects.

Abstract

Isavuconazonium sulfate is the water‐soluble prodrug of the novel, broad‐spectrum, triazole antifungal agent isavuconazole. A size 0 elongated hard capsule containing 100 mg equivalent of isavuconazole is the currently marketed oral formulation in countries where it is approved. An alternative oral formulation, based on a lower‐strength and smaller‐size capsule, is required for pediatric and adolescent patients, as well as for some adult Japanese patients, especially those with difficulties swallowing larger capsules. This study was conducted to evaluate the bioequivalence of a size 0 elongated capsule containing 100 mg equivalent of isavuconazole and a size 3 capsule containing 40 mg equivalent of isavuconazole, after administration of 200 mg equivalent of isavuconazole (5 size 3 capsules or 2 size 0 elongated capsules) under fasted conditions. Bioequivalence of isavuconazole between the formulations was demonstrated, since point estimates (90%CI) for the ratio of the size 0 elongated capsules vs the size 3 capsules for maximum plasma concentration and area under the plasma concentration–time curve from time 0 to the last quantifiable concentration were within the acceptable range of 0.8 to 1.25. It was confirmed that both formulations were well tolerated, and no new safety signals were observed in healthy Japanese adult male subjects.