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Pharmacokinetics, Pharmacodynamics, and Safety of Vadadustat in Healthy Volunteers and Patients with Chronic Kidney Disease.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Jun 25. Date of Electronic Publication: 2024 Jun 25. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). Single ascending dose (SAD) and multiple ascending dose (MAD) studies assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of vadadustat in healthy volunteers. A single-dose, open-label study was conducted in patients with CKD stages 3 and 4 not on dialysis. In the SAD study, 48 healthy adult men (n = 8/cohort) received single doses of vadadustat (80-1,200 mg) or placebo. In the MAD study, 34 healthy adult men (n = 8-9/cohort) received daily vadadustat (500-900 mg) or placebo for 10 days. In the single-dose CKD study, 22 male and female patients with CKD (stage 3: n = 10; stage 4: n = 12) received single doses of vadadustat (500 mg). PK parameters included plasma vadadustat; PD biomarkers were measured, including erythropoietin (EPO) levels, reticulocytes, and others. Plasma vadadustat peaked 3-4 hours after single or multiple dosing in healthy volunteers, with a mean t <subscript>1/2</subscript> of approximately 4.5 hours. In patients with CKD, plasma vadadustat peaked at 5-6 hours, with a mean t <subscript>1/2</subscript> of 7.2 (stage 3) and 8.5 (stage 4) hours. Vadadustat AUC <subscript>∞</subscript> and C <subscript>max</subscript> increased dose proportionally in SAD and MAD trials. In all trials, EPO concentrations increased in a dose-related manner and returned approximately to baseline by 24 hours. Adverse events were mild and considered not study drug related. The PK and PD results of these studies were utilized for further clinical development of vadadustat for treatment of anemia in CKD patients.<br /> (© 2024 Akebia Therapeutics, Inc. and The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Details
- Language :
- English
- ISSN :
- 1532-6535
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 38924087
- Full Text :
- https://doi.org/10.1002/cpt.3342