Evaluation of drug-drug interactions of pemigatinib in healthy participants.

Purpose: Pemigatinib (INCB054828), a potent and selective oral fibroblast growth factor receptor 1-3 inhibitor, is a Biopharmaceutical Classification System class II compound with good permeability and pH-dependent solubility that is predominantly metabolized by cytochrome P450 (CYP) 3A. Two drug-drug interaction studies, one with acid-reducing agents, esomeprazole (proton pump inhibitor [PPI]) and ranitidine (histamine-2 [H2] antagonist), and the other with potent CYP3A-modulating agents, itraconazole (CYP3A inhibitor) and rifampin (CYP3A inducer), were performed.

Methods: Both were open-label, fixed-sequence studies conducted in up to 36 healthy participants each, enrolled into two cohorts (n = 18 each).

Evaluation of the pharmacokinetics of pemigatinib in patients with impaired hepatic or renal function.

Aims: Pemigatinib, an inhibitor of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases, is approved for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma. Pemigatinib is predominantly metabolized by CYP3A4 with minimal renal elimination.

Methods: Separate hepatic and renal impairment studies were conducted to evaluate the effect of these impairments on pemigatinib pharmacokinetics (PK).

Effect of Hepatic Impairment on the Pharmacokinetics of Itacitinib.

Itacitinib is a potent, selective JAK-1 inhibitor currently in development for the treatment of chronic graft-vs-host-disease in combination with corticosteroids. Itacitinib is primarily eliminated via cytochrome P450 3A metabolism with minimal renal elimination. The purpose of this open-label study was to investigate the effect of hepatic impairment, as determined by Child-Pugh grade, on itacitinib pharmacokinetics.