First-In-Human (FIH) clinical trials represent a critical stage in which a new drug is administered to humans for the first time, aiming to determine the optimal initial dose that prioritizes patient safety while offering the potential for therapeutic benefit. Based on nonclinical pharmacokinetic/pharmacodynamic (PK/PD) modeling results, we predict the FIH dose to minimize uncertainties in clinical entry and support a successful trial initiation.

FIH dose prediction goes beyond simply applying a safety factor to the No-Observed-Adverse-Effect Level (NOAEL) obtained from nonclinical studies. We utilize nonclinical PK/PD models and apply interspecies extrapolation techniques that account for differences in drug response across animal species. Through this process, we analyze how the pharmacodynamic activity of the drug is likely to manifest in humans, and predict both the minimum effective dose and the maximum tolerated dose.

By establishing the initial dose based on an understanding of the drug’s mechanism of action and target receptor, we provide a more scientific and precise rationale than relying solely on toxicology data. This approach delivers essential insights for predicting and managing potential drug-related adverse effects, while offering the optimal starting point for exploring the drug’s potential efficacy in the early stages of clinical trials.

First-In-Human (FIH) clinical trials must prioritize patient safety and play a pivotal role in designing safety-based, precise dose-escalation schemes, as well as establishing thorough safety monitoring plans. Together, these two factors provide essential information for the successful conduct of early-stage clinical trials and for establishing subsequent clinical development strategies.

The dose-escalation design in First-In-Human (FIH) clinical trials goes beyond simply increasing the dose step by step. It is a process of exploring the safest and most effective initial dose range for patients, based on the safety and pharmacokinetic (PK) / pharmacodynamic (PD) data obtained from nonclinical studies.

In the initial stage, a Single Ascending Dose (SAD) study is conducted, administering gradually increasing doses to a small group of healthy volunteers to assess the drug’s safety and tolerability. Based on the drug’s characteristics and the initial safety data, a Multiple Ascending Dose (MAD) study is then planned to evaluate safety, pharmacokinetics (PK), and early pharmacodynamic (PD) responses of the drug under repeated dosing conditions. At this stage, the dose-escalation range and the criteria for transitioning to the next dose level are defined to minimize patient risk.

Alongside dose-escalation design, a systematic safety monitoring plan is equally essential. We develop tailored monitoring strategies by comprehensively considering the drug’s mechanism of action, nonclinical toxicology data, and anticipated adverse events. Through this safety-based, precise dose-escalation design combined with comprehensive safety monitoring, we ensure patient safety as the top priority in First-In-Human (FIH) clinical trials and establish a solid foundation for the successful progression to the next stages of new drug development.