Assessment of Food Effect and pH‐Dependent Drug–Drug Interactions of Fruquintinib in Healthy Subjects

• Published in: Clinical and translational science Vol. 18; no. 3; pp. e70168 - n/a
• Main Authors: Gonzalez, Martha, Yang, Zhao, Schelman, William R., Zhou, Xiaofei, Gupta, Neeraj, Chien, Caly
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2025; John Wiley and Sons Inc; Wiley
• Subjects: Administration, Oral; Adolescent; Adult; Area Under Curve; Benzofurans - administration & dosage; Benzofurans - adverse effects; Benzofurans - pharmacokinetics; Cross-Over Studies; Dosage; Drug dosages; Drug interaction; Drug Interactions; drug–drug interaction; Fasting; Female; Food; Food-Drug Interactions; fruquintinib; Healthy Volunteers; Hepatitis; Humans; Hydrogen-Ion Concentration; Kinases; Male; Microbiota; Middle Aged; Permeability; pH reducing; Pharmacokinetics; proton pump inhibitor; Proton pump inhibitors; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - pharmacokinetics; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - pharmacokinetics; rabeprazole; Rabeprazole - administration & dosage; Rabeprazole - pharmacokinetics; Reducing agents; Vascular endothelial growth factor; Young Adult; pH reducing; pharmacokinetics; drug–drug interaction; rabeprazole; proton pump inhibitor; fruquintinib
• DOI: 10.1111/cts.70168
• ISSN: 1752-8054; 1752-8062

ABSTRACT This two‐sequence, three‐period study (NCT04645940) was designed to evaluate the effect of food and concomitant rabeprazole, a proton pump inhibitor, on the pharmacokinetics (PK) and safety of fruquintinib and its metabolite M11 after a single oral dose of fruquintinib 5 mg in healthy subjects. In the food effect treatment periods, 14 subjects were randomized in a 1:1 ratio utilizing a two‐sequence (fed/fasted vs. fasted/fed), two‐period, cross‐over design. Fruquintinib was administered on Day 1 (Period 1) and Day 15 (Period 2). In the drug‐interaction period (Period 3), all subjects received rabeprazole 40 mg 1 h prior to fruquintinib under fasted conditions, following a 6‐day lead‐in of rabeprazole 40 mg once daily. PK samples to measure fruquintinib and M11 were collected pre‐dose and over 168 h after fruquintinib dosing. Administration of fruquintinib with a high‐fat meal resulted in similar systemic exposure compared with fasted conditions. In addition, coadministration of fruquintinib with rabeprazole resulted in similar exposure compared with fruquintinib alone. For both evaluations, 90% confidence intervals for the ratio of geometric least square mean of the area under the curve and peak concentration for fruquintinib and M11 were entirely within 80%–125% bounds. The study results showed no effects of food or rabeprazole on fruquintinib PK, and support that fruquintinib can be taken without regard to food or concurrent gastric acid‐reducing agents.