A Single-Blind, Randomised, Placebo-Controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Inhaled Londamocitinib (AZD4604) Following Single Ascending and Multiple Doses in Healthy Japanese and Chinese Participants

Background/Objectives: This study seeks to evaluate the safety, tolerability and pharmacokinetics of londamocitinib, an inhaled selective Janus kinase 1 (JAK-1) inhibitor, in healthy Japanese and Chinese participants after administration of single and multiple doses. Methods: A two-part, single-blind, placebo-controlled Phase 1 study was conducted, which included healthy male and female adult Japanese and Chinese participants who received single ascending doses (1 mg to 4 mg) or multiple doses of 3 mg twice daily of inhaled londamocitinib for 7 days. Results: A total of 32 Japanese and 24 Chinese participants were enrolled and dosed. No severe or serious adverse events were noted, and londamocitinib exhibited an acceptable safety and tolerability profile. After single and multiple doses, londamocitinib was rapidly absorbed, with maximal plasma concentration (Cmax) reached at a median time ranging from 0.07 to 0.1 h post-dose, and post-maximal plasma concentrations declined in a biphasic manner. In Japanese participants, Cmax increased with dose in an approximately dose-proportionate manner, and total drug exposure (AUCinf) increased in a less than dose-proportionate manner following single doses. In Chinese participants, dose proportionality was not explored. Accumulation of londamocitinib following twice-daily dosing was not different in Japanese and Chinese participants, ranging from a 3.50- to 3.54-fold increase in the area under the curve within the dosing interval (AUCtau) and a 1.63- to 1.89-fold increase in Cmax. Steady state was achieved after approximately 6 days based on geometric mean and individual trough concentrations. Conclusions: Londamocitinib’s pharmacokinetic, safety and tolerability profiles in Japanese and Chinese participants were consistent with previous results in healthy participants. The observed PK profiles do not suggest clinically meaningful ethnic differences requiring dose adjustment.