Introduction: SHR0302 is a highly selective JAK1 inhibitor. This study aimed to investigate the safety, tolerability, and pharmacokinetics of single and multiple-dose topical skin application of SHR0302 base ointment in healthy adult subjects. Methods: This phase I clinical trial (registration number: CTR20192188) consisted of two parts. Part 1 was a single-dose ascending study with four dose levels in 32 healthy Australian adults (8 subjects in each dose group). All Australian subjects were randomized 3:1 to a single-dose topical skin application of SHR0302 base ointment or placebo. The dose escalated from 1% SHR0302 base ointment on 3% of body surface area (BSA) to 2% SHR0302 base ointment on 20% of BSA. Part 2 combined single and multiple-dose ascension studies with two dose levels in 20 healthy Chinese adults (10 subjects in each dose group). All Chinese subjects were randomized 4:1 to a combination of single and multiple doses for consecutive 10 days of topical application of 1% SHR0302 base ointment on 20% BSA or 2% SHR0302 base ointment on 20% BSA. The safety and pharmacokinetics of the SHR0302 base ointment were evaluated. Results: The incidence of treatment-emergent adverse events (TEAEs) in both parts was comparable between the SHR0302 base ointment group and the vehicle group (part 1: 33.3% vs. 37.5%; part 2: 56.3% vs. 75.0%). All TEAEs were transient, recovered, and equally well-tolerated in the two racial groups. The overall absorption of the SHR0302 base ointment was slow after topical application, with Tmax>10 h. After a single dose of the SHR0302 base ointment, drug exposure in healthy Australian and Chinese subjects increased nonlinearly with the increase in the administration area and drug content. Drug exposure increased in a less-than-dose-proportional manner within the dose range tested. Due to differences in the clinical practice of topical application, the Tmax of the drug in Australian subjects was earlier than in Chinese subjects, but the overall extent of absorption seemed comparable in Australian and Chinese subjects (with comparable AUC0-t). Conclusion: The SHR0302 base ointment (either single or multiple doses) was well tolerated and safe, with no racial disparity. Key Message: The SHR0302 base ointment (either single or multiples doses) was well tolerated and safe.

Yao X, Song ZQ, Li W, Liang YS, Zhao Y, Cao H, et al. Guidelines for diagnosis and treatment of atopic dermatitis in China (2020)#. Int J Dermatol Venereol. 2021 Mar;4(1):1–9.
Wang X, Li LF, Zhao DY, Shen YW. Prevalence and clinical features of atopic dermatitis in China. Biomed Res Int. 2016;2016:2568301.
Chinese Society of Dermatology Immunology Group. Atopic dermatitis working group. [Guidelines for the diagnosis and treatment of atopic dermatitis in China (2014)](article in Chinese). Chin J Dermatol. 2014;47(7):511–4.
Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017 Apr;77(5):521–46.
Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. Jakstat. 2013 Jul 1;2(3):e24137.
Cotter DG, Schairer D, Eichenfield L. Emerging therapies for atopic dermatitis: JAK inhibitors. J Am Acad Dermatol. 2018 Mar;78(3 Suppl 1):S53–62.
Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020 Feb;145(2):572–82.
Nusbaum KB, Nguyen CM, Fleischer AB Jr. Emerging systemic therapies for atopic dermatitis: oral small molecules and targeted topical agents. J Dermatolog Treat. 2022;33:1274–8.
Hsu L, Armstrong AW. JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014:283617.
Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395.
Harrington R, Al Nokhatha SA, Conway R. JAK inhibitors in rheumatoid arthritis: an evidence-based review on the emerging clinical data. J Inflamm Res. 2020 Sep 14;13:519–31.
Olivera PA, Lasa JS, Bonovas S, Danese S, Peyrin-Biroulet L. Safety of janus kinase inhibitors in patients with inflammatory bowel diseases or other immune-mediated diseases: a systematic review and meta-analysis. Gastroenterology. 2020 May;158(6):1554–73.e12.
Singh R, Heron CE, Ghamrawi RI, Strowd LC, Feldman SR. Emerging role of janus kinase inhibitors for the treatment of atopic dermatitis. Immunotargets Ther. 2020 Nov 10;9:255–72.
Lachenmeier DW. Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. J Occup Med Toxicol. 2008 Nov 13;3:26.
Kouchak M, Handali S. Effects of various penetration enhancers on penetration of aminophylline through shed snake skin. Jundishapur J Nat Pharm Prod. 2014 Feb;9(1):24–9.
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