1354. Novel Formulation SUBA-Itraconazole in Fed and Fasted Healthy Volunteers: Expanding the Clinical Utility of the Established Mold Active Agent

Abstract

Background. Itraconazole has been established as an effective mold active agent; however, wide interpatient variability in bioavailability and poor gastrointestinal tolerability have made using the agent challenging. A novel formulation, SUBAItraconazole (SUperBioAvailable) has been developed by Mayne Pharma to alleviate these negative properties. Methods. An open-label, randomized, cross-over study of SUBA-Itraconazole capsules 65 mg (2 × 65 mg BID) in healthy adults under fasting and fed conditions was assessed for steady-state levels. Subjects (n = 20) were administered two capsules of SUBA-Itraconazole twice daily on Days 1-14 and once on the morning of Day 15, either on an empty stomach or with a meal. Safety was monitored by vital signs measurements, electrocardiogram measurements, clinical safety laboratory tests (liver and kidney function tests), and physical examination. Results. Overall, SUBA-Itraconazole demonstrated similar concentrations at the end of the dosing interval (trough), with modestly lower total and peak exposure when administered under fed conditions compared with the fasted state (fed/fasted ratios of 78.09% for AUC [14,183.2 vs. 18,479.8] 73.05% for C max,ss [1,519.1 vs. 2,085.2] and 91.53% for C [1,071.5 vs. 1,218.5]); see Figures 1 and 2. The administration of SUBA-Itraconazole 65 mg capsules was well-tolerated by the healthy subjects participating in this study. Conclusion. The results demonstrate a promising clinical utility for SUBA- Itraconazole in practice. Unlike the conventional capsule formulation which requires a high fat meal for absorption, or the oral solution formulation which requires a fasted administration, SUBA-Itraconazole reached a therapeutic steady state in both fasted and fed states. The similar trough level, however higher peak with fasted state, likely represents a more gradual absorption of drug in the fed state. The slightly higher bioavailability in a fasted state, without gastrointestinal intolerability, is particularly promising for the clinical use of SUBA-Itraconazole in patients unable to have a high fat content meal due to chemotherapy or post-surgery such as hematology patients and transplant recipients. (Figure Presented).