Preclinical Update: Regulatory Guidelines & Dose Determination

This lecture covers the current regulatory guidelines for determining appropriate first-in-human (FIH) clinical doses using preclinical data, including FDA and EMA guidance. It discusses endpoints like MABEL and NOAEL, as well as strategies to identify and mitigate risks in FIH trials. The lecture also explores the impact of drug exposure on subjects, the MABEL approach in dose selection, and the use of PK-PD modeling in dose escalation. Additionally, it delves into the considerations for single and multiple ascending doses, sentinel dosing, and the design of FIH trials with multiple objectives.