MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial.

Background: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis).
Methods: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180.
Results: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 ( P = .03) and 14 ( P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications ( P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001).
Conclusions: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra.
Clinical Trials Registration: NCT03572049.
Competing Interests: Potential conflicts of interest. A. S. reports research funding from Astellas and Mayne and consulting fees from GSK and F2G. As deputy editor for Open Forum Infectious Diseases, per journal policy, A. S. was not involved in the peer review or editorial decision process for this article. G. R. T. reports research support and consulting fees from Astellas, Cidara, F2G, Mayne, Melinta, Merck, and Scynexis and served as a consultant for Pfizer. M. H. M. has received research funding from Mayne, F2G, and Scynexis and consulting fees from Astellas, Scynexis, and PSI. J. H. reports research funding from Mayne. L. A. M. is an employee of Mayne Pharma. P. G. P reports research funding from Mayne, Astellas, Scynexis, Melinta, and Cidara and consulting fees from Matinas, Melinta, and F2G. All other authors report no potential conflicts.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)