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.