Overview:
The transition from preclinical experiments to first in human clinical trials signifies a significant milestone in the development of any new drug candidate. The first-in- human (FIH) study evaluates an investigational medicinal product (IMP) in humans for the first time, focusing on assessing its safety, tolerability, and human pharmacology (PK/PD) of the molecule. Typically, a FIH study involves single ascending dose and multiple ascending doses to establish the appropriate dosing range for further development. A thorough understanding of the molecule’s characteristics and behavior in humans, including dose-response relationship, safety signals, and key PKPD parameters, facilitated by the right study design and accurate execution, is crucial for informed decision-making.
Following the FIH study, depending on existing knowledge about your asset, you may be confronted with the need to run an absorption, metabolism and excretion (AME) study in order to de-risk liabilities resulting from drug metabolism or elimination. This requires timely preparations, and choices to be made.
FIH studies provide excellent data with which to initiate PK and PK/PD modelling which can then be used to support study design and dose selection for future studies. This is particularly the case where PD/biomarker and ECG assessments have been performed and also where these studies include one or more patient cohorts.
During this webinar we discussed the following topics:
Cohort planning and dose selection in first-in-human (FIH) studies
- The main objectives and essential components of FIH studies
- Strategic approach for FIH study design and recommended methods for dose selection
Options for running a hAME study
- The various approaches to running a hAME study including: AME or ABA as part of the first FIH study, microtracer or “high dose AME”, and the differences in the conduct of hAME studies across geographic regions
Progression into early patient studies
- Insights into the considerations involved in selecting the appropriate population for early clinical development and transitioning into patient studies
Pharmacometric analyses using data from FIH studies
- Population PK modelling
- PK/PD modelling
- Concentration-QTc modelling
Speakers:
Jocelyn Courville
Jocelyn is a Senior Director of Clinical Pharmacology at ICON. Before joining ICON, she served as a global clinpharm program lead at several major pharma companies, where she supervised a range of drug programs. Jocelyn skilfully offers guidance to customers on optimal trial design, dose selection, PK/PD assessment, and other intricate clinical pharmacology related data analysis and execution strategies.
Ad Roffel
Ad is a Senior Director of Clinical Pharmacology at ICON. He is involved in advising and supporting our customers with respect to drug development, including the design of studies, PK and PD parameters, inclusion/exclusion criteria, and ethics. Focus areas have been thorough QT studies, respiratory medicine, and 14C microdosing and AME studies.
Colm Farrell
Colm heads up ICON’s global Quantitative Pharmacology & Pharmacometrics (QP&PMx) team which covers all phases of drug discovery and development. The team are passionate about the application of Model-Informed Drug Development and Discovery (MID3) to optimize clinical drug development programs.