国产聚乙二醇化重组人粒细胞集落刺激因子注射液Ⅰ期临床耐受性研究

Tolerability of Hypodermic Injection of Pegfilgrastin(PEG-G-CSF) in a Phase I Study

目的评价健康人体对国产聚乙二醇化重组人粒细胞集落刺激因子(PEG-G-CSF)注射液的耐受性和安全性。方法健康志愿者30例随机分入单次给药组。单次给药分别皮下注射PEG-G-CSF注射液15、30、50、60、75μg/kg,观察临床症状、体征,包括体温、脉搏、呼吸频率、血压等指标;实验室检查包括血常规、尿常规、肝肾功能、心电图等。结果50μg/kg组10例志愿者中1例出现一过性轻度头晕;75μg/kg组有6例志愿者用药后均出现一过性轻度的头晕和骨痛,其中1例志愿者出现一过性高热,2例志愿者出现一过性轻度腹泻,但试验结束时复查均未发现有临床意义的实验室检查和心电图异常。结论本研究结果提示,健康受试者对PEG-G-CSF注射液的最大耐受剂量为60μg/kg,在此范围内使用安全性和耐受性好,并能明显刺激中性粒细胞和CD34+细胞增加。II期临床研究推荐剂量为皮下注射60μg/kg,每化疗周期给药1次。

Objective To evaluate the safety and tolerance of pegfilgrastin （PEG-G-CSF） in Chinese healthy volunteers. Methods Thirty healthy volunteers were randomly divided into five single-dose groups to receive PEG-G- CSF 15, 30, 50, 60 or 75μg/kg by hypodermic injection. The safety profile and tolerability were evaluated by observing symptoms, vital signs, laboratory tests and electro cardiogram. Results No serious adverse event was reported for any volunteer. Transient dizziness occurred in one person in the 50 μg/kg dose group, and mild dizziness and ostalgia was found in all six people in the 75μg/kg dose group, of whom one experienced transient fever and two experienced mild diarrhea. No clinically significant changes in laboratory tests and electrocardiogram were found during the follow-up period. Conclusions The maximum tolerated dose of PEG-G-CSF injection in Chinese healthy volunteers is 60 μg/kg. Doses below 60 μg/kg can be well tolerated. The recommended dose for phase II clinical trials is 60 μg/kgone, one dose for each cycle of chemotherapy.