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M1. Clinical studies of fungal infections
Poster Session: Medical Mycology
Rezafungin (RZF) is a novel echinocandin antifungal being developed for treatment of candidemia and invasive candidiasis, and for prevention of invasive fungal diseases among immunosuppressed patients. In the Phase 2 and Phase 3 treatment trials of rezafungin compared with caspofungin (STRIVE [NCT02734862] and ReSTORE [NCT03667690], respectively), patients with severe hepatic impairment (HI) were not included due to lack of caspofungin data in this population. Rezafungin was previously evaluated in patients with moderate hepatic impairment. Here we report an open-label, single-dose study on rezafungin in patients with HI (Child-Pugh class C).
To investigate the safety, tolerability, and pharmacokinetics (PK) of RZF in subjects with HI and healthy subjects (HS), 8 subjects with HI and 8 HS matched for age, sex, and body mass index (BMI) were enrolled and received a single 400-mg intravenous 1-hour infusion of RZF. Plasma PK sampling was performed at various time points through 336 hours postdose. RZF PK parameters were derived using non-compartmental analysis. Safety was assessed throughout the study.
The majority of the HI subjects were White (87.5%) and male (75%) while equal distribution between White and Black or African American was observed among HS (50%) and 75% were male. The mean age of HI subjects was 58 years (range, 41–68 years) and 56.6 years (range, 50–61 years) for the HS. Mean BMI was 29.7 kg/m2 (range, 24.5–34.3 kg/m2) for HI subjects and 29.7 kg/m2 (range, 25.4–34.2 kg/m2) for the HS. RZF exposure (Cmax and AUC) in subjects with HI was ~30% lower than that in HS (Table 1), while half-life was generally similar (HI: 121 h, HS:124 h; Figure 1). Three HI subjects had one adverse event (AE) each (bronchitis, worsening hepatic encephalopathy, hyponatremia), all moderate in severity; one HS had 1 AE of infusion site infiltration mild in severity. No AEs were considered related to RZF, and all were resolved or resolving by the end of the study.
RZF was well tolerated in HI subjects and showed modestly reduced exposure that was within the range observed in matched HS. These findings support no RZF dose adjustment in subjects with severe hepatic impairment.
Jade Huguet, Ph.D.
Director Clinical Pharmacology
Altasciences
Montreal, Quebec, Canada
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Voon Ong, PhD
Executive Director, Preclinical Development
Cidara Therapeutics, Inc.
San Diego, California, United States
Disclosure: Cidara Therapeutics (Employee, Shareholder)
Taylor Sandison, MD, MPH
Chief Medical Officer
Cidara Therapeutics, Inc.
San Diego, California, United States
Disclosure: Cidara Therapeutics (Employee, Shareholder)
Rebeca M. Melara, M.S.
Principal Scientist
Altasciences
Culver City, California, United States
Disclosure: Altasciences (contract research organization) (Employee)
Thomas C. Marbury, MD
President
Orlando Clinical Research Center
Orlando, FL, United States
Disclosure: Orlando Clinical Research Center (Employee, Other Financial or Material Support, Equity owner of Orlando Clinical Research Center)
Alena Jandourek, MD
N/A
San Diego, California, United States
Disclosure: Cidara therapeutics (Consultant)
Shawn Flanagan, PhD
VP, Clinical Pharmacology and Early Development
Cidara Therapeutics, Inc.
San Diego, California, United States
Disclosure: Cidara Therapeutics (Employee, Shareholder)