The Relative Bioavailability and Effects of Food and Acid-Reducing Agents on Filgotinib Tablets in Healthy Subjects.

ABSTRACT

Filgotinib is a potent, selective Janus kinase-1 inhibitor being developed to treat chronic inflammatory diseases. This phase 1 study in healthy subjects evaluated the relative bioavailability of filgotinib maleate tablets versus the reference tablet (filgotinib hydrochloride) and effects of food and acid-reducing agents (ARAs) on the pharmacokinetics of filgotinib and its major metabolite. Noncompartmental pharmacokinetic parameters of filgotinib and its major metabolite were compared between the 2 tablets at 100- and 200-mg doses and with or without food or ARAs. Filgotinib maleate tablets resulted in equivalent plasma exposures (area under concentration-time curve to infinity [AUC∞ ] and maximum concentration [Cmax ]) of filgotinib and its metabolite as the reference tablet (90%CIs of geometric least-squares mean ratios were within the prespecified no-effect boundary of 70% to 143%). Food intake had no effect on filgotinib AUC∞ , but a high-fat meal reduced Cmax by 20%. Coadministration of filgotinib with omeprazole or famotidine had no effect on filgotinib AUC∞ , but omeprazole decreased Cmax by 27%. Neither food nor ARAs affected metabolite exposure. Single-dose filgotinib 100 or 200 mg was well tolerated. This study supports evaluation of filgotinib maleate tablets, administered without regard to food or ARAs, in future clinical studies.