Evaluation of Potential Food Effects and Drug Interactions With Lansoprazole in Healthy Adult Volunteers Receiving Futibatinib. Issue 3 (16th November 2022)

• Record Type: Journal Article
• Authors: Yamamiya, Ikuo; Hunt, Allen; Yamashita, Fumiaki; Sonnichsen, Daryl; He, Yaohua; Benhadji, Karim A.
• Is Part Of: Clinical pharmacology in drug development. Volume 12:Issue 3(2023)
• Page Start: 294
• Page End: 303
• Publication Date: 2022-11-16
• Subjects: FGFR‐aberrant tumors -- food effect -- futibatinib -- pharmacokinetics -- PPI effect; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.1196
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: Futibatinib, an oral, irreversible fibroblast growth factor receptor (FGFR) 1–4 inhibitor, is being evaluated for FGFR ‐aberrant tumors. Two open‐label phase 1 studies evaluated the effects of high‐fat, high‐calorie food and concomitant proton pump inhibitors (PPIs; lansoprazole) on single‐dose futibatinib (20 mg) pharmacokinetics and safety in healthy adults. In the food effect study (N = 17), subjects received futibatinib under fed and fasted conditions, separated by a 7‐day washout. In the PPI study (N = 20), subjects received futibatinib alone, underwent a 2‐day washout, and then received lansoprazole 60 mg once daily for 5 days, with futibatinib also administered on day 5. Under fed versus fasted conditions, futibatinib bioavailability was 11.2% lower (area under the plasma concentration–time curve from time 0 to infinity geometric mean ratio 88.8%; 90% confidence interval, 79.8%–98.9%), and median time to maximum plasma concentration was significantly delayed (4.0 vs 1.5 hours; P < .0001). There were no significant differences in futibatinib exposure between futibatinib plus lansoprazole and futibatinib alone. No serious adverse events occurred in either study. These findings suggest that food and PPIs are unlikely to have clinically meaningful impacts on futibatinib bioavailability. Thus, futibatinib may be used with or without food and concomitantly with acid‐reducing agents.