Wang Fangfang, Niu Xiaoye, Liu Na, Zhu Zhengying, Lin Yun, Ying Lisa, Li Haiyan
Peking University Third Hospital, Beijing, China.
Everest Medicines, Shanghai, China.
Front Pharmacol. 2025 Jun 2;16:1523339. doi: 10.3389/fphar.2025.1523339. eCollection 2025.
Etrasimod is an investigational, oral, once-daily, selective S1P 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.
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 multiple-dose periods. Cohort 3 received multiple-dose etrasimod 2 mg or placebo, followed by titration to 3 mg or placebo. Cardiac monitoring included 24-h 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.
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 h. 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.
http://www.chinadrugtrials.org.cn, identifier: CTR20190003.
埃曲莫德是一种正在研发的口服、每日一次的选择性1-磷酸鞘氨醇（S1P）受体调节剂，用于治疗免疫介导的炎症性疾病。我们展示了埃曲莫德在中国健康成年人中的安全性、耐受性、药代动力学和药效学结果。
在一项1期随机、双盲、安慰剂对照、剂量递增研究中，中国健康成年受试者被随机分配到3个队列。队列1和队列2分别给予单剂量埃曲莫德1毫克或2毫克，或安慰剂，随后进行洗脱期，然后是多剂量期。队列3接受多剂量埃曲莫德2毫克或安慰剂，随后滴定至3毫克或安慰剂。心脏监测包括24小时动态心电图、心电图监测和12导联心电图。主要终点是安全性和耐受性，次要终点是对埃曲莫德的药代动力学和药效学反应。
所有治疗中出现的不良事件严重程度均为《不良事件通用术语标准》1级，所有事件均无需医疗干预即可缓解。最常见的事件是窦性心动过缓（心率<50次/分钟），所有这些事件均无症状。未报告感染或感染相关事件。对埃曲莫德的药代动力学和药效学反应与先前在其他人群中的研究一致。多剂量给药时，埃曲莫德的暴露量至少与剂量成比例增加，半衰期在28.1至37.9小时之间。埃曲莫德剂量依赖性地降低淋巴细胞计数，这些减少主要见于初始T细胞、中枢记忆T细胞和辅助性T细胞。
在单剂量和多剂量期，高达3毫克的埃曲莫德在中国健康受试者中安全且耐受性良好。
