OBJECTIVES: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population. METHODS: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. RESULTS: Out of 27 subjects enrolled, 7 receivedibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. CONCLUSIONS: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.
RCT Entities:
OBJECTIVES: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population. METHODS: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. RESULTS: Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. CONCLUSIONS: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.
Authors: Martin Hoenigl; Rosanne Sprute; Amir Arastehfar; John R Perfect; Cornelia Lass-Flörl; Romuald Bellmann; Juergen Prattes; George R Thompson; Nathan P Wiederhold; Mohanad M Al Obaidi; Birgit Willinger; Maiken C Arendrup; Philipp Koehler; Matteo Oliverio; Matthias Egger; Ilan S Schwartz; Oliver A Cornely; Peter G Pappas; Robert Krause Journal: Expert Opin Investig Drugs Date: 2022-06-15 Impact factor: 6.498
Authors: Guillermo Quindós; Katherine Miranda-Cadena; Rosario San-Millán; Katyna Borroto-Esoda; Emilia Cantón; María José Linares-Sicilia; Axel Hamprecht; Isabel Montesinos; Anna Maria Tortorano; Anna Prigitano; Matxalen Vidal-García; Cristina Marcos-Arias; Andrea Guridi; Ferran Sanchez-Reus; Jesús Machuca-Bárcena; Manuel Antonio Rodríguez-Iglesias; Estrella Martín-Mazuelos; Carmen Castro-Méndez; Leyre López-Soria; Alba Ruiz-Gaitán; Marcelo Fernandez-Rivero; Damaris Lorenzo; Javier Capilla; Antonio Rezusta; Javier Pemán; Josep Guarro; Joana Pereira; Célia Pais; Orazio Romeo; Guillermo Ezpeleta; Nerea Jauregizar; David Angulo; Elena Eraso Journal: Front Cell Infect Microbiol Date: 2022-05-16 Impact factor: 6.073
Authors: Mahmoud Ghannoum; Maiken Cavling Arendrup; Vishnu P Chaturvedi; Shawn R Lockhart; Thomas S McCormick; Sudha Chaturvedi; Elizabeth L Berkow; Deven Juneja; Bansidhar Tarai; Nkechi Azie; David Angulo; Thomas J Walsh Journal: Antibiotics (Basel) Date: 2020-08-25