Abstract: 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 Emax. 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.

Key words: He-wei-zhi-xie capsule, diarrhea, clinical study, population pharmacodynamics model, post-marketing re-evaluation