Pharmacokinetics, Safety, and Tolerability of Single- and Multiple-Dose Once-Daily Baricitinib in Healthy Chinese Subjects: A Randomized Placebo-Controlled Study.

Abstract

The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once‐daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 through 10. Safety and tolerability were also assessed. Baricitinib was rapidly absorbed, reaching peak plasma concentrations within 0.5 to 1 hour (median). Plasma concentrations declined rapidly following the attainment of peak concentrations, with a mean terminal half‐life of 5.7 to 7.3 hours. Steady‐state plasma concentrations of baricitinib were achieved after the second day of once‐daily dosing, with minimal accumulation of baricitinib in plasma (up to 10% increase in area under the plasma concentration–time curve). Single‐ and multiple‐dose mean values for area under the plasma concentration–time curve from time zero to infinity and maximum plasma concentration appeared to increase in an approximately dose‐proportional manner across the dose range. Single and multiple oral doses of once‐daily baricitinib up to 10 mg were well tolerated by healthy Chinese subjects.