Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection

Clin Pharmacokinet. 2015 Feb 14. [Epub ahead of print]

Filgotinib (GLPG0634) is a selective inhibitor of JAK1 currently in development for the treatment of RA and Crohn’s disease. This paper describes the pharmacokinetics of filgotinib and its active metabolite, as well as the PK/PD modelling to support dose selection for phase IIB.

Two phase I, randomised, double-blind, placebo-controlled trials in healthy volunteers and one phase IIa proof-of-concept study in RA patients were used to evaluate single and multiple doses of filgotinib.

Results showed dose-dependent pharmacodynamic activity of combined filgotinib and its metabolite. Filgotinib was extensively and rapidly absorbed after single and repeated oral dosing in healthy volunteers. While PK/PD modelling and simulation showed a maximal pharmacodynamic effect achieved at daily dosing of 200 mg. This dose has now been selected as the highest dose in the phase IIb programme for filgotinib.