七竭止痛片Ⅰ期临床耐受性试验

Phase I Clinical Tolerability Trial of Qijie Zhitong Tablets

目的评价健康志愿者对口服七竭止痛片的耐受性。方法 48例健康志愿受试者随机分为单次给药组4组（剂量分别为3,6,9,12片,每个试验组设安慰剂对照组2例）和多次给药组2组（剂量分别为6,9片,连续7 d）,观察用药前后受试者生命体征、心电图和血生化指标的变化,并观察和记录药物不良事件。结果单次给药后24 h内,有6例受试者出现口干（4例,均为第4组）或头晕头痛（4例,其中第2组、第3组各1例,第4组2例）,症状较轻微,未给予特殊处理,均于数小时内自行缓解,判定与试验药物可能有关;2例受试者（第2组、第3组各1例）出现血压降低,2例受试者（第1组、第4组各1例）出现心电图改变,均轻微,判定可能与试验药物无关。多次给药试验中,7例受试者出现异常,其中3例（第2组）体温升高（37.1～37.4℃）,1例（第2组）头痛,2例（第2组）视物模糊,4例（第1组3例,第2组1例）心电图改变,均轻微,未行干预自行缓解,判定可能与试验药物有关。结论七竭止痛片不良事件主要有头晕、头痛、口干、视物模糊、发热、心电图异常,主要发生于单次给药12片组和多次给药9片组,建议Ⅱ期临床试验中,应严格选择中医证候和适宜疗程,最大日给药量不超过9片,并在试验期间密切观察神经系统、循环系统、消化系统的不良反应。

Objective To evaluate the tolerability of healthy subjects to Qijie Zhitong Tablets. Methods Forty-eight cases of healthy volunteers were randomly divided into single dose groups（receiving single oral dose of Qijie Zhitong Tablet 3, 6, 9, 12 tablets respectively, involved 8 cases in the placebo） and multiple dose groups （receiving daily oral dose of 6 and 9 tablets for seven days respectively）. The variety of vital signs, electrocardiogram（ECG） and serum biochemical indicators were observed before and after treatment, and the adverse events were also monitored. Results Within 24 h after the single dose, 6 cases had mild dry-mouth （4 cases）, dizziness or headache （4 cases）. The symptoms were relieved spontaneously in a few hours, indicating that the symptoms were correlated with the study drug. Blood pressure was decreased in two subjects, and ECG changes were also shown in 2 subjects, and the symptoms were slight and proved not to be related with the study drug. In the multiple dose test, 7 subjects had abnormal manifestations, of which 3 cases had elevated temperature （37.1-37.4 ℃ ）, one case had headache, 2 cases had blurred vision, 4 cases had ECG changes. All of the above adverse action was mild, and was relieved spontaneouslywithout intervention, which was probably related with the study drug. Conclusion The adverse events of Qijie Zhitong Tablets mainly involve dizziness, headache, dry mouth, blurred vision, fever, and abnormal ECG, and usually occur in the single dose of 12 tablets group and multiple dose of 9 tablets group. It is suggested that in phase Ⅱ clinical trial, TCM syndrome types and appropriate treatment course should be strictly chosen, the maximum daily dose should be not more than 9 tablets, and the adverse reaction of nervous system, circulatory system, digestive system should be closely monitored during the test.