舒络粉针剂Ⅰ期临床耐受性试验

Phase Ⅰ tolerability trial of Shuluofenzhen

目的:观察舒络粉针剂在健康志愿者中的安全性和耐受性。方法:单次给药剂量组32例健康志愿者被分为7个剂量组,各组例数分别为2,4,6,6,6,4,4,分别给予舒络粉针剂2.0,6.0,8.0,10.0,12.0,14.0,16.0 g.d-1。多次给药剂量组12例健康志愿者被分为2个剂量组,每组6例,分别给予舒络粉针剂6.0 g或10.0 g,qd,连续给药7 d。观察受试者的生命体征、实验室检查、心电图检查及不良事件。结果:共44例健康志愿者完成了耐受性试验。单次、多次试验中均未发生严重不良事件及过敏反应。生命体征、大小便常规、肝功能、肾功能、凝血功能及心电图均未发现异常。44例受试者中发生4例(6例次)不良事件,其中3例为白细胞减少,与试验药物可能有关。结论:舒络粉针剂在2.0～16.0 g.d-1范围内用药的安全性和耐受性良好,单次给药的最大耐受剂量为16.0 g.d-1。多次给药6.0 g及10.0 g.d-1,qd,连续给药7 d的耐受性较好。推荐II期临床试验的给药方案为6.0～10.0 g.d-1。

Objective： To assess the tolerability and safety of Shuluofenzhen in Chinese healthy volunteers.Methods： Thirty-two healthy subjects were enrolled in the single-dose study.Each subject was administered one of the 7 doses of 2.0,6.0,8.0,10.0,12.0,14.0 and 16.0 g·d^-1by intravenous injection.There were 2,4,6,6,6,4 and 4 subjects in each dose group.Twelve healthy subjects were enrolled in the multiple-dose trial.The subjects in the lower dose group were administered 6.0 g and the subjects in the higher dose group were administered 10.0 g Shuluofenzhen by intravenous injection once a day for consecutive 7 days.There were 6 subjects in each groups.The safety was evaluated based on clinical symptoms,vital signs,physical examinations,ECG,laboratory tests and adverse events.Results： Forty-four healthy volunteers completed the study.No serious adverse event and clinically significant changes in vital signs,ECG and laboratory tests were found in both single-dose groups and multiple-dose groups.In 44 subjects,there were 4（6 cases） adverse events.Low white blood cell counts were observed in 3 subjects,which were mild,transient,and recovered spontaneously.Conclusion： Shuluofenzhen is safe and well-tolerated in Chinese healthy subjects after administration of single-doses（2.0-16.0 g·d^-1 and multiple-doses（6.0-10.0 g·d^-1 once a day for consecutive 7 days.The maximal tolerated dose of Shuluofenzhen is 16.0 g·d^-1in the single-dose trial.The dose regimen of 6.0-10.0 g·d^-1is recommended for phase II study.