白细胞介素-1受体阻滞剂滴眼液耐受性研究

Phase I clinical trial of an eyedrop recombinant human interleukin-1 receptor antagonist

目的:评价白细胞介素-1受体阻滞剂(IL-1Ra)滴眼液在中国健康人的安全性和耐受性。方法:依据其临床前安全资料确定初剂量及最大剂量,评价其安全性。采用单次给药、连续多次给药的方法,观察用药后生命体征、眼局部安全指标和全身安全性指标。结果:IL-IRa的耐受性试验未引起受试者全身、局部症状的异常,未引发不良反应症状。结论:IL-1Ra滴眼液在25～100μg·mL-1范围内,人体耐受性良好。推荐进行Ⅱ期临床试验的用药剂量及疗程为50μg·mL-1滴眼液qid,每次0．05 mL,共用药5 d。

Objective： To evaluate the tolerance and safety of an eyedrop recombinant human interleukin-1 receptor （rhIL-1） antagonist in Chinese healthy people. Methods： The initial dosage and maximal tolerance close were evaluated in an open and close taper clinical study setting. Chinese healthy subjects were dropped with a once-giving dose （25μg·mL^-1, 50μg·mL^-1 or 100μg·mL^-1） and multigiving doses （50μg·mL^-1） of the eyedrop. The safety and tolerance were assessed based on body responses, eye safe index and physical and lab outcomes. Results： No local or systemic abnormalities were found after dropping the rhIL-1 antagonist. The subjects were tolerated well at the dosing range of 25 100μg·mL^-1. Conclusion： The recommended dosing in phase Ⅱ trial is to use 50μg·mL^-1 of the eyedrop to apply four times per day, 0.05 mL each, for 5 days.