静脉注射尖吻蝮蛇血凝酶Ⅰ期临床耐受性研究

 目的　在中国健康成年志愿者中评价单剂和多剂静注国家注册一类新药注射用尖吻蝮蛇血凝酶的安全性、耐受性。方法　按GCP要求设计试验方案。单剂耐受性试验将30例受试者随机区组分至0.5～6U共5个剂量组,每组6例,男女各半,从最低剂量组开始给药,当所有单剂静注剂量组确证安全耐受后,方可开始多剂静注耐受性试验。多剂耐受性试验入选 10例健康男性受试者,静注尖吻蝮蛇血凝酶1U,qd,连续4d。观察指标为临床症状、体征和实验室检查指标等。应用方差分析进行数据统计学处理。结果　单剂静注尖吻蝮蛇血凝酶耐受性试验中,各组受试者入选时各项指标均在正常范围,条件均衡,具较好可比性。试验中仅发现2例与药物可能有关的轻度一过性可耐受不良反应,分别表现为凝血酶元活性动度(PA),部分凝血活动酶时间(aPTT)轻度降低和全血黏度升高,未见其他有临床意义的改变。多剂耐受性试验中亦未见严重不良反应,仅发现2例全血黏度升高的轻度一过性不良反应,停药后1d内全部自行恢复正常。结论　30名健康受试者分别单剂静注尖吻蝮蛇血凝酶,最大剂量至6U,10名健康受试者多剂静注尖吻蝮蛇血凝酶,比较安全、耐受性较好。

Phase Ⅰ clinical tolerability of heamocoagulase agkistrodon injection

OBJECTIVE To evaluate the safety and tolerability of single dose and multi dose injection of heamocoagulase agkistrodon(HCA)in Chinese healthy volunteers.METHODS The protocol was designed according to the Good Clinical Practice(GCP).30 healthy volunteers of 18～50 years old were randomly divided into five dosage groups from 0.5 U to 6 U with three males and three females in each group.10 healthy male volunteers were administered HCA injection 1U once a day for 4 days.Clinical symptoms,vital signs and laboratory tests were recorded before and after injection of HCA to evaluate the adverse reactions Analysis of variance was applied to get statistical result.RESULTS After single-dose injection of HCA, most vital signs,clinical symptoms and laboratory tests were normal. There were no significant clinical changes or severe ADRs. Only two cases of slight and tolerable ADRs which were probably related to the drug were observed One case was slight PA and aPTT reduction and the other was whole blood viscosity elevation No severe ADRs were observed after multi dose injection of heamocoagulase agkistrodon Only two cases of slight whole blood viscoity increas were observed The two subjects both recovered one day after withdrawal.CONCLUSION Single-dose up to the maximum dose of 6 U and multi dose of HCA injection were safe and tolerable.