32333 Clinical and pharmacokinetic results of upadacitinib in Chinese healthy subjects and subjects with moderate-to-severe atopic dermatitis

Abstract

Background/objective: Upadacitinib is a Janus kinase 1 selective inhibitor being investigated to treat atopic dermatitis (AD). Efficacy and safety of upadacitinib in AD and its pharmacokinetic profile have not been established in Chinese population. Methods: Subgroup analyses on Chinese population were performed for Measure Up 1 (NCT03569293) and AD Up (NCT03568318). A pharmacokinetic study, M15-558 (CTR20170243), was also conducted in 36 Chinese healthy subjects. Twelve subjects in 3 groups each were randomized 3:1 to receive upadacitinib 15 mg, 30 mg, 45 mg or placebo once daily for 7 days. Results: Similar to the corresponding global population, the proportion of patients who achieved EASI 75 and vIGA-AD 0/1 at week 16 in Chinese subpopulation of Measure Up 1 (N = 45) and AD Up (N = 51) was numerically higher for both upadacitinib doses vs. placebo (15 mg: 78.6%, 64.3%; 30 mg: 76.5%, 47.1%; placebo: 14.3%, 7.1% in Measure Up 1; 15 mg+TCS: 70.6%, 41.2%; 30 mg+TCS: 87.5%, 50.0%; placebo+TCS: 27.8%, 0% in AD Up). In M15-558, median Tmax of upadacitinib ranged from 3 to 4 hours and terminal elimination t1/2 ranged from 6.6 to 9.8 hours. Upadacitinib steady-state Cmax (ng/mL) and AUC0-24 (ng•h/mL) were dose-proportional after multiple doses of 15 mg (56.2 ± 9.76, 431 ± 93.2), 30 mg (103 ± 24.5, 878 ± 241), and 45 mg (168 ± 28.5, 1220 ± 241), consistent with the previously observed exposures in Western subjects. All upadacitinib doses were well tolerated. Conclusions: Upadacitinib pharmacokinetics were similar among Chinese healthy subjects and Western population. Consistency regarding efficacy and safety was also observed between Chinese and global AD patients.