Abstract

Fenebrutinib (GDC-0853) is an orally administered small molecule inhibitor of Bruton's tyrosine kinase being investigated for treatment of rheumatoid arthritis (RA) 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 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 to 20, subjects received 200 mg fenebrutinib twice daily. On Day 21, subjects received a 7.5 mg dose of MTX and a 200 mg dose of fenebrutinib under fasting conditions. The geometric mean ratios of MTX AUC and Cmax on Day 21 relative to Day 1 (90% 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 methotrexate trials. These results indicate that there is no clinically significant pharmacokinetic interaction between fenebrutinib and MTX. SIGNIFICANCE STATEMENT: N/A.

View details for DOI 10.1124/jpet.119.257089

View details for PubMedID 31371481