A Phase 1, Open-Label, Single-Dose Study of the Effect of Hepatic Impairment on the Pharmacokinetics of Erdafitinib, an FGFR Inhibitor

一项关于肝功能损害对FGFR抑制剂厄达替尼药代动力学影响的1期、开放标签、单剂量研究

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Abstract

Erdafitinib, an oral pan-FGFR inhibitor is extensively metabolized in the liver. This open-label, single-dose, phase 1 study evaluated the pharmacokinetics (PK) of erdafitinib in participants with hepatic impairment versus healthy controls. Overall, 26 participants were enrolled. Following a single 6 mg oral dose, the maximum plasma concentration (C(max)) of total erdafitinib was reached at median t(max) of 3 h across all groups (participants with mild hepatic impairment, moderate hepatic impairment, and control). The geometric mean ratios for free C(max) and free AUC(∞), were 96.07% and 95.22% in participants with mild hepatic impairment compared with controls, respectively. The geometric mean ratios for free C(max) and free AUC(∞), were 104.8% and 87.51% in participants with moderate hepatic impairment compared with controls, respectively. Single oral doses of erdafitinib were well tolerated across all cohorts, and no new safety signals were noted. The results demonstrate that dose adjustments are not necessary in participants with mild or moderate hepatic impairment receiving oral erdafitinib.

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