和胃止泻胶囊治疗腹泻患者的临床疗效和模型化评价

Clinical efficacy and modeling evaluation of He-wei-zhi-xie capsules in treating diarrhea patients

目的:进一步评价和胃止泻胶囊上市后扩大用药人群范围对腹泻患者的临床疗效和安全性,对和胃止泻胶囊治疗腹泻的疗效特征进行模型化评价并考察协变量对药效的影响。方法:采用多中心、前瞻性、开放、非对照性的临床研究设计方法,于2015年10月至2017年12月,在全国35家临床试验中心开展和胃止泻胶囊上市后临床安全性再评价研究。主要疗效指标为止泻有效率,次要疗效指标为腹泻复常率、腹泻复常时间、不成型大便次数和Leeds消化不良症状量表评分。采用非线性混合效应模型建立和胃止泻胶囊时间进程的药效学模型,考察协变量对药效参数的影响。安全性指标为不良事件和不良反应发生率及实验室检查指标。结果:纳入全分析集(FAS)分析的病例共2 285例,止泻有效率为90.8%,腹泻复常率为77.3%,腹泻复常中位时间均为3 d,用药后3 d Leeds消化不良症状量表评分减少3.6分。建模发现用药前每天便质不正常次数对模型参数E_(max)有显著的影响。最终模型参数E_(max)为6次/d, ET_(50)为2.19 d。基线值对参数E_(max)的校正系数为1.61,即基线每增加1次/d,E_(max)值增加1.61次/d。试验期间共发生不良事件146例,不良事件发生率为6.39%,其中13例判断为不良反应,不良反应发生率为0.57%。试验期间共发生严重不良事件2例,严重不良事件发生率为0.09%,无严重不良反应发生。结论:和胃止泻胶囊能有效减少腹泻患者的腹泻次数,并且不良反应发生率较低,是一种值得推广的治疗药物。

AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie(HWZX) capsules in diarrhea patients. METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter E_(max). A total of 146 cases of adverse event and 13 cases of adverse reaction were observed in the experiment. Adverse event ratio was 6.39%, and adverse reaction ratio was 0.57%. There were 2 cases of serious adverse event with 0.09% of serious adverse event ratio and no serious adverse reaction case. CONCLUSION: HWZX capsules can effectively reduce the number of diarrhea, and has a low incidence of adverse reactions and high safety in this study, which is a therapeutic drug worthy of promotion.