Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Etrasimod in Healthy Chinese Adults: A Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Phase 1 Study

Fangfang Wang¹Xiaoye Niu¹Na Liu¹Zhengying Zhu²Yun Lin²Lisa Ying²Haiyan Li^1*

• ¹Peking University Third Hospital, Haidian, Beijing Municipality, China
• ²Everest Medicines, Shanghai, China

Objectives: Etrasimod is an investigational, oral, once-daily, selective S1P1,4,5 receptor modulator in development for the treatment of immune-mediated inflammatory diseases. We present safety, tolerability, pharmacokinetic, and pharmacodynamic results of etrasimod treatment in healthy Chinese adults.Methods: In a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation study, healthy Chinese adult subjects were randomly assigned to 3 cohorts. Cohorts 1 and 2 were given single-dose etrasimod, 1 mg or 2 mg, respectively, or placebo, followed by washout, then multipledose periods. Cohort 3 received multiple-dose etrasimod 2 mg or placebo, followed by titration to 3 mg or placebo. Cardiac monitoring included 24-hour dynamic electrocardiogram, electrocardiogram monitoring, and 12-lead electrocardiogram. The primary endpoints were safety and tolerability, and secondary endpoints were pharmacokinetic and pharmacodynamic responses to etrasimod.Results: All treatment-emergent adverse events were Common Terminology Criteria for Adverse Events Grade 1 in severity, and all events were resolved without medical intervention. The most frequent event was sinus bradycardia (heart rate < 50 bpm), and all these events were asymptomatic. No infections or infection-related events were reported. Pharmacokinetic and pharmacodynamic responses to etrasimod were consistent with previous studies in other populations. Etrasimod exposure increased at least dose proportionally for multiple doses and exhibited a half-life between 28.1 and 37.9 hours. Etrasimod dose-dependently reduced lymphocyte counts, and these reductions were primarily seen in T naïve, T central memory, and T helper cells.Etrasimod was safe and well-tolerated in healthy Chinese subjects up to 3 mg in single and multiple-dose periods.