The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers

Mod J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.

Current biologic therapies for RA, such as biologic cytokine inhibitors, which selectively target inflammatory molecules with an exquisite degree of specificity, are not clinically effective in all patients with rheumatoid arthritis. As such, there remains an unmet clinical need for more effective and better tolerated therapies. Baricitinib (LY3009104, also previously known as INCB028050) is a potent and selective small molecule inhibitor of JAK1/2, which play an important role in cytokine signalling.

This report summarises the findings of the first-in-human and single ascending dose and multiple ascending doses studies of baricitinib. Two double-blind, randomised, and placebo-controlled studies were conducted to evaluate single ascending doses of 1–20 mg and multiple ascending doses of 2–20 mg QD and 5 mg BID for 10 or 28 days in healthy volunteers.

Baricitinib demonstrated a favourable pharmacokinetic and pharmacodynamics profile suitable for once-daily administration, with an overall safety profile supporting its further clinical development.