P515 Comparability of upadacitinib pharmacokinetics in Japanese and non-Japanese subjects with ulcerative colitis with the extended-release formulation

Abstract Background Upadacitinib (UPA), an oral selective JAK1 inhibitor, is being developed for treatment of patients with moderately-to-severely active ulcerative colitis (UC) in addition to several other inflammatory diseases. UPA has shown favourable efficacy and acceptable safety in UC in an 8-week double-blind placebo-controlled dose-ranging Phase 2b induction study in subjects with moderately-to-severely active UC (U-ACHIEVE trial). Methods Sparse blood samples were collected from subjects with UC who were enrolled in the U-ACHIEVE trial, which included Japanese and non-Japanese subjects. UPA plasma concentration vs. time after dose were summarised from the U-ACHIEVE trial. Additionally, data from U-ACHIEVE were pooled with data from UPA Phase 1 and other Phase 2 studies across different inflammatory diseases to characterise UPA population pharmacokinetics. The population pharmacokinetic model was used to estimate UPA plasma exposures from extended-release formulation (dose range 7.5 – 45mg QD) in 168 non-Japanese and 28 Japanese subjects with UC in U-ACHIEVE. Results UPA plasma exposures were approximately dose proportional over the evaluated dose range in Japanese subjects with UC. Observed dose-normalised plasma concentrations vs. time since the last dose (Figure 1) and dose-normalised model-estimated UPA exposures were comparable (within 25%) between Japanese and non-Japanese subjects with UC (Table 1). Conclusion UPA plasma exposures are similar between Japanese and non-Japanese subjects with UC. This is in agreement with prior assessments in healthy subjects and in subjects with RA which demonstrated comparable UPA exposures between Asian and Western subjects.