CRED Understanding Clinical Development 2024

11/10/2024

Design and Guidelines for First in Human Studies

European Medicines Agency

Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products 20 July 2017 EMEA/CHMP/SWP/28367/07 Rev. 1 Committee for Medicinal Products for Human Use (CHMP)

Food and Drug Administration (FDA, USA)

Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers July 2005 Pharmacology and Toxicology

Guidance for Industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals January 2010 Revision 1

Guidance for Industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals March 2010 ICH

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PK (and PK/PD) has increasing relevance as indicated in recent guidance

…A state -of-the-art PK/PD modelling approach is recommended, taking into consideration repeated dose applications as to be expected in the clinical situation.

… All available non-clinical information (PD, PK, TK, and toxicological profiles, dose or exposure/effect relationships, etc.) should be taken into consideration for the calculation of the starting dose, dose escalation steps, and maximum dose. Furthermore, clinical data (e.g., PK, PD, and reports of adverse events) emerging during the trial from previous dosed cohorts/individuals needs to be taken into account, in line with pre-specified decision criteria.

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