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

Abstract

BackgroundItraconazole 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, SUBA-Itraconazole (SUperBioAvailable) has been developed by Mayne Pharma to alleviate these negative properties.MethodsAn 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.ResultsOverall, 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 AUCtau [14,183.2 vs. 18,479.8] 73.05% for Cmax,ss [1,519.1 vs. 2,085.2] and 91.53% for Ctrough[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.ConclusionThe 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 1.Mean pre-dose plasma itraconazole concentrations.Figure 2:Mean plasma itraconazole concentration–time profile (day 15).Disclosures J. Lindsay, Mayne Pharma: Consultant, Consulting fee. S. Mudge, Mayne Pharma: Employee, Salary.