Effects of Food, Gastric Acid Reduction, and Strong CYP3A Induction on the Pharmacokinetics of Tasurgratinib, a Novel Selective Fibroblast Growth Factor Receptor Inhibitor

We conducted this three-part study in healthy subjects to investigate the pharmacokinetics of tasurgratinib (orally available selective inhibitor of fibroblast growth factor receptor 1-3) and M2 (its major metabolite) under different conditions. In Part A, subjects received tasurgratinib 35 mg either fed with a high-fat meal or fasted. In Parts B and C, subjects received tasurgratinib 35 mg alone or with either rabeprazole (acid-reducing agent) 20 mg (Part B) or rifampin (strong CYP3A inducer) 600 mg (Part C). Primary endpoints were maximum concentration (C_max), and areas under the plasma concentration-time curve to time of last quantifiable concentration (AUC_(0-t)) and extrapolated to infinite time (AUC_(0-inf)). Forty-two subjects were enrolled, 14 each into Parts A, B, and C. In Part A, administration of tasurgratinib with a high-fat meal resulted in 33% reduction in C_max and ∼23% reduction in AUC_(0-t) and AUC_(0-inf) of tasurgratinib, and 47% reduction in C_max with ∼30% reduction in AUC_(0-t) and AUC_(0-inf) of M2. In Part B, co-administration of rabeprazole at steady state resulted in no/weak interaction with tasurgratinib (∼8% increase in AUC_(0-t) and AUC_(0-inf) without an effect on C_max) and M2 (∼18% increase in AUC_(0-t) and AUC_(0-inf) without an effect on C_max). In Part C, co-administration of rifampin at steady state resulted in a weak interaction with tasurgratinib (∼16% reduction in AUC_(0-t) and AUC_(0-inf)) and M2 (∼12% reduction in AUC_(0-t) and AUC_(0-inf)). Administration of tasurgratinib with a high-fat meal appeared to reduce systemic exposure of tasurgratinib, however co-administration with an acid-reducing agent or a CYP3A inducer had a minimal impact on pharmacokinetics.