Kunhong Deng, Jie Huang, Qian Wu, Jinlian Xie, Xiaoyan Yang, Shuang Yang, Lu Liu, Yafang Gong, Wanyao Shen, Ling Cai, Guoping Yang, Chengxian Guo
Introduction HZ-J001 is a novel topical tofacitinib tartrate cream designed to optimize local pharmacokinetics (PKs) and minimize systemic adverse events (AEs). This study aimed to evaluate the safety, tolerability, and PK characteristics of HZ-J001 cream in healthy Chinese subjects. Methods This randomized, double-blind, placebo-controlled Phase Ia trial included both single-ascending-dose (SAD) and multiple-dose (MD) phases. Healthy subjects were enrolled into 5 sequential cohorts (10 HZ-J001 and 2 placebo per cohort). SAD Cohorts 1-3 received single doses of HZ-J001 cream at strengths of 1.0%, 1.5%, and 2.0%, respectively, each applied to a fixed area of 20% body surface area (BSA) (3,200 cm 2 ). SAD Cohort 4 received the 2.0% strength applied to a larger area of 30% BSA (4,800 cm 2 ). MD Cohort 5 received the 2.0% strength to 30% BSA (4,800 cm 2 ) twice daily for 8 days and once on Day 9 (17 doses in total). A fixed amount of 3 mg cream/cm 2 was applied for all subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated. Results A total of 61 subjects were enrolled and 60 received study drug. HZ-J001 cream was well-tolerated and no serious TEAEs or discontinuations occurred. The most common TEAEs by system organ class were investigations. Local tolerability was acceptable, with only mild application-site reactions reported. Systemic exposure following single-dose administration was low (C max and AUC 0-t were 0.09–0.16 ng/mL and 7.24–12.18 h·ng/mL, respectively). Although drug accumulation occurred after repeated dosing (accumulation ratios: 15.71 for C max and 28.80 for AUC 0-τ ), overall systemic exposure remained low. Conclusion HZ-J001 cream demonstrated a favorable safety profile and a PK characteristic of minimal systemic exposure in healthy subjects, supporting its further development as a topical therapy for atopic dermatitis.