冠心病新药黄芪总苷氯化钠注射液Ⅰ期人体耐受性临床研究

Safety and Tolerance of Healthy People to Injection of Astragalosides——a New Drug for Coronary Heart Disease

中文关键词:  冠心病 黄芪总苷 Ⅰ期 耐受性临床研究

英文关键词:Coronary heart disease Total astragalosides Phase Ⅰclinical trial Safety and tolerance study

中文摘要:

      目的 观察健康受试者对黄芪总苷氯化钠注射液的安全性和耐受性，为该药Ⅱ期临床试验安全的用药剂量范围提供参考。方法 选择62例健康受试者为研究对象，依次开展单次给药和连续给药耐受性临床试验。其中单次给药26例，设6个剂量组，分别为100 mL、200 mL、300 mL、400 mL、500 mL和600 mL，每日给药1次，静脉滴注。多次给药36例，设4个剂量组，分别为500 mL、400 mL、300 mL和200 mL，每日给药1次，连续给药7 d。观察指标：服药期间和服药结束后3 d或7 d后的不适症状、生命体征和安全性指标等，进行统计分析。结果 62例健康受试者共有31例出现40例次不良事件，23例次判断为轻度不良反应，4例次中度不良反应。其中单次给药剂量有9例受试者出现9例次不良事件，7例次不良反应；多次给药500 mL、400 mL剂量组10例14例次不良事件，9例12例次不良反应；多次给药300 mL、200 mL剂量组12例17例次不良事件，判断为轻度不良反应为3例次。不良反应主要表现为：肝功能异常（谷丙转氨酶、谷草转氨酶、血清总胆红素的轻度升高），血钾偏低，尿红细胞计数升高，皮疹，静脉炎等。结论 Ⅰ期耐受性临床试验单次给药最大耐受量为600 mL；多次给药7 d，每日最大耐受量为400 mL，建议Ⅱ期临床试验参考本实验结果设计剂量分组，观察其对冠心病患者治疗的临床疗效及安全性。

英文摘要:

      Objective To assess the safety and tolerance of healthy volunteers to as tragalosides injection (AGI), and to determine a safe dose range for phase Ⅱ clinical trial. Methods A total of 62 healthy volunteers participated in this study, with 26 being given a single AGI of 100 mL, 200 mL, 300 mL, 400 mL, 500 mL, or 600 mL and 36 subjects being given 500 mL, 400 mL, 200 mL or 300 mL of AGI once a day for 7 d. Discomfortsymptoms, vital signs and safety problems were recorded 3 d and 7 d after the administration of AGI. The results were analyzed. Results Of the 62 participants, 40 adverse events (AEs) were reported by 31 participants, which included 23 mild adverse reactions (ADRs) and 4 moderate ADRs. Nine AEs were reported by 9 participants with single AGI, including 7 ADRs. Fourteen AEs were reported by 10 participants with 500 mL and 400 mL multiple AGI, including 12 ADRs occurred in 9 participants.Seventeen AEs were reported by 12 participants with 300 mL and 300 mL multiple AGI, including 3 mild ADRs. The main ADRs included abnormal liver function 〔slightly elevated glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum total bilirubin (TBil)〕, low blood potassium, increased urine red blood cell count, rash, and phlebitis. Conclusion The maximum tolerance is 600 mL for single-dose treatment, and 400 mL for multiple-dose (7 d). The dose guidance given in this study should be examined its effects and safety in patients with coronary heart disease in phase Ⅱ clinical trial.