南五味子软胶囊Ⅰ期人体耐受性临床研究

Phase Ⅰ human tolerance clinical study of Nanwuweizi softcapsule

目的:考察人体对南五味子软胶囊的耐受性和初步安全性,为该药Ⅱ期临床试验提供安全的剂量范围。方法:选择健康人为受试者,依据动物实验结果推算初始及最大剂量,从安全的初始剂量开始,顺序开展单次给药耐受性试验和累积性耐受性试验。共纳入36例受试者,其中单次给药耐受性临床试验24例,5个剂量组,分别为1(含南五味子木脂素提取物132mg g)、2、3、4、6粒,每日1次给药。累积性(多次给药)耐受性试验12例,2个剂量组,分别为4粒/次和3粒/次,每日1次,连续给药7天。观察指标为临床症状、生命体征和理化检查指标等,采用SAS 9.13统计软件进行统计学处理。结果:36名受试者共发生15例次轻度不良反应,主要表现为:血清白/球蛋白(A/G)轻度下降、CD3+、CD4+、CD8+降低,大便隐血弱阳性,血清总胆红素升高,血AST轻度升高,血Cl-降低,等。结论:南五味子软胶囊Ⅰ期临床试验最大耐受剂量单次给药为4粒/日,多次给药为3粒/日。推荐Ⅱ期临床试验的安全剂量范围为每日3粒,建议在Ⅱ期临床试验中注意对不良反应的观察。

Aim： objective to investigate the tolerance of human body of Nanwuweizi softcapsule and preliminary safety,for the drug Ⅱ phase of clinical trial to provide a safe dose range. Methods： choose healthy human subjects,according to the results of animal experiments,calculate the initial and maximum dose,starting from the initial dose of the security,order to carry out the single drug resistance test and cumulative tolerance test. Single drug tolerance test： 24 cases of single drug susceptibility of clinical trials,five dose groups,respectively,1（ including south five ZiM u lipid extract 132 mg g）,2,3,4,6,1 times a day. Cumulative（ multiple dosing） tolerance test： 12 cases,2 dose groups,respectively bead / and 3 /4 times,1 times a day,for seven days in a row. Observation indexes for clinical,vital signs and physical and chemical inspection index,using SAS 9. 13 statistical software for statistical processing. Results 36 subjects A total of 15 cases of adverse reactions,main show is： blood innocence / globulin（ A / G） mild decline,CD3^＋,CD4^＋,CD8^＋,defecate occult blood weakly positive,higher serum total bilirubin,moderately elevated blood AST,Cl is reduced,blood,etc. Conclusion： Nanwuweizi softcapsule Ⅰ phase of the maximum tolerated dose single drug clinical trials of 4 / day. Many times to give medicine for 3 grain / day. Recommend Ⅱ the safe dose range of clinical trials is 3 per day,recommended in Ⅱperiod pay attention to the observation of the adverse reactions in clinical trials.