Abstract
AIMS: Filgotinib (GS-6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohn's disease. The aim of the present study was to investigate the impact of age and renal impairment (RI) on the pharmacokinetics (PK) of filgotinib and its main metabolite. METHODS: The effect of age was assessed in two groups of 10 elderly healthy subjects (65-74 and ≥75 years of age) and a control group of 10 younger healthy subjects (40-50 years of age). The impact of RI was investigated in three groups of subjects with mild (n = 6), moderate (n = 6) and severe (n = 3) RI [estimated glomerular filtration rate (eGFR) 60-89, 30-59 and 15-29 ml min(-1) 1.73 m(-2) , respectively] and a control group (n = 9) with normal renal function (eGFR ≥90 ml min(-1) 1.73 m(-2) ). The PK of filgotinib and its metabolite were evaluated following filgotinib 100 mg once-daily doses for 10 days. RESULTS: At steady state, the exposure [area under the concentration-time curve over the dosing interval (AUC(0-24 h) )] of filgotinib and its metabolite was moderately higher (1.45- and 1.33-fold, respectively) in the elderly subjects (≥75 years) compared with younger subjects. Renal clearance for filgotinib and its metabolite decreased with the degree of RI, leading to a maximum increase in AUC(0-24 h) of 1.54-fold for filgotinib and 2.74-fold for the metabolite in subjects with severe RI. Filgotinib was generally safe and well tolerated. CONCLUSIONS: Age and mild to moderate impairment of renal function had limited impact on the PK of filgotinib. In subjects with severe RI, the exposure to the metabolite of filgotinib was elevated, consistent with its renal elimination pathway.