Absence of Pharmacokinetic Interactions between the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib and Methotrexate.

Fenebrutinib (GDC-0853) is an orally administered small molecule inhibitor of Bruton's tyrosine kinase being investigated for treatment of rheumatoid arthritis in patients with inadequate responses to methotrexate (MTX). This study interrogated the potential for pharmacokinetic drug interactions between fenebrutinib and MTX. Eighteen healthy male subjects were enrolled in the study. They received a single oral dose of MTX (7.5 mg) on day 1 followed by a 13-day washout period. Subsequently, on days 15-20 the participants received 200 mg of fenebrutinib twice daily. On day 21, they received a 7.5 mg dose of MTX and a 200 mg dose of fenebrutinib under fasting conditions. The geometric mean ratios of MTX area under the plasma concentration-time curve (AUC) and C _max on day 21 relative to day 1 (90% confidence interval [CI]) were 0.96 (0.88-1.04) and 1.05 (0.94-1.18), respectively. The geometric mean ratios of fenebrutinib AUC and C _max for day 21 relative to day 20 (90% CI) were 1.03 (0.95-1.11) and 1.02 (0.90-1.15), respectively. The combination treatment was well tolerated, with an adverse event profile similar to that reported in other MTX trials. These results indicate that there is no clinically significant pharmacokinetic interaction between fenebrutinib and MTX.
(Copyright © 2019 The Author(s).)