Abstract
Results of nonclinical toxicity studies play an important role in risk management for subjects in clinical trials. It is important to verify and improve the predictability of adverse events through toxicity studies to minimize risks to subjects.
Adverse events in the GI tract, such as diarrhea and constipation, are observed frequently in clinical trials. The GI events in clinical area are known to decrease medication adherence. In this presentation, we will report the results of a survey on the predictability of toxicity studies for adverse events in the GI tract, targeting recently approved small molecule drugs (anti-neoplastic drugs, antidiabetic drugs, etc.).
Based on the approval information, we have selected new drugs and we extracted GI adverse events related to the investigational drug from CTD, interview forms, RMP materials, etc. And we investigated whether similar findings had been observed in the toxicity studies.
In the results, diarrhea or constipation were observed as adverse events affecting the GI tract in the clinical. In the toxicity studies, findings related to these adverse events were observed in the many drugs, regardless of indication. The results showed that diarrhea and constipation were highly predictive. And the results were similar to previous reports that toxicity studies for small molecule drugs were highly predictive of diarrhea and constipation. The reasons for this high predictability are thought to be that there are no major species differences in the physiological functions of the GI tract, and that the dose settings for toxicity studies were optimized.
