广金钱草总黄酮胶囊Ⅰ期临床耐受性和安全性研究

Study on Phase I Clinical Tolerance and Safety of Total Flavonoids of Herba Desmodii Styracifolii Capsules

目的:评价健康受试者单次和多次口服广金钱草总黄酮胶囊的临床安全性和耐受性。方法:本研究共选取64例健康受试者,男女各半,其中54例受试者随机双盲法分配到单次给药试验组,共分7个剂量组(剂量分别为133、399、798、1197、1596、1995、2394 mg),每剂量组人数(试验药+安慰剂)分别为4(4+0)、4(4+0)、6(6+0)、10(8+2)、10(8+2)、10(8+2)和10(8+2)例;10例(8+2)受试者进入连续多次给药试验组,给药剂量为一次665 mg,3次/日,连续10 d。给药前后对全部入组受试者的血常规、尿常规、血生化、ECG、凝血功能进行定时检测,并记录生命体征。结果:64例受试者全部完成研究且无严重不良反应。单次给药试验组46例受试者中有9例(19.6%)和安慰剂组8例受试者中有2例(25.0%)均出现了轻度不良反应;连续给药试验组8例受试者中有6例(75%)和安慰剂组2例中有1例(50%)出现轻度不良反应;上述出现的不良反应,受试者均转归,且研究者判断为与试验药物可能无关。结论:健康人体单日单次口服广金钱草总黄酮胶囊不超过2394 mg或连续服药665 mg/次,3次/日,具有较好的安全性和耐受性。建议Ⅱ期临床试验使用剂量不高于665 mg/次,3次/日。

Objective： To evaluate the safety and tolerance of single dose and multiple dose total flavonoids of Herba Desmodii Styracifolii capsules by oral administration in healthy subjects. Methods： A randomized, double-blind, placebo- controlled study was conducted in 64 eligible subjects （ female ： male = 1 ： 1 ）. The proportion of experiment group and placebo group was 80%. 54 eligible subjects were divided to 7 dosages in single dose group, the number of subjects（ experiment group ＋placebo group） were 4（4 ＋0）, 4（4 ＋0）, 6（6 ＋0）, 10（8 ＋2）, 10（8 ＋2）, 10（8 ＋2） and 10（8 ＋2）, respectively. 10 eligible subjects were distributed to multiple dose group, the number of subjects （ experiment group ＋ placebo group） were 10 （8 ＋ 2 ）. Safety and tolerability were evaluated by monitoring adverse events and laboratory parameters containing blood routine, urine routines, blood biochemistry, ECG examination, blood clotting function. Result： 64 people all completed the study and no serious adverse events occurred. In the single dose group, 9 cases of experiment group occurred mild adverse events（ 19.6% , 9/46）, 2 cases of placebo group occurred mild adverse events（25.0% , 2/8） ; In the multiple dose group, 6 people of experiment group occurred mild adverse events （75.0% , 6/8）, 1 people of placebo group occurred mild adverse events（50. 0%, 1/2）; All adverse events were judged as no-drug-related by the investigators. Conclusion： Total flavonoids of Herba Desmodii Styracifolii capsule was safe and well tolerated with single dose of less than 2394 mg per single day or multiple dose of 665 mg（ 1/8 h） in Chinese subjects. The suggested dosage of II-phase clinical trial was no higher than 665 mg per time, 3 times a day.