TY - JOUR T1 - Absence of Pharmacokinetic Interactions between the Bruton’s Tyrosine Kinase Inhibitor Fenebrutinib and Methotrexate JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 202 LP - 207 DO - 10.1124/jpet.119.257089 VL - 371 IS - 1 AU - Nicholas Steven Jones AU - Helen Winter AU - Tamiko R. Katsumoto AU - Marilyn Florero AU - Elaine Murray AU - Helen Walker AU - Nand Singh AU - Leslie W. Chinn Y1 - 2019/10/01 UR - http://jpet.aspetjournals.org/content/371/1/202.abstract N2 - 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 Cmax 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 Cmax 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. ER -