Interpreting all guidelines before your first-in-human clinical trials can be overwhelming. While guidelines are helpful, they should not be read like instruction manuals that can be applied the same way to every project. It’s even possible that certain guidelines do not apply to your project at all! Therefore, guidelines need to be customized to fit your unique project. Before diving headfirst into the guidelines, read on for tips to help you understand the essential regulatory requirements leading up to first-in-human clinical trials.
Essential regulatory requirements before first-in-human clinical trials
First-in-human clinical trials are performed to study the safety and tolerability of an investigational medicinal product. This will lay the foundation for all forthcoming clinical evaluations. The main priority is to ensure the safety for trial participants, and all preceding development work aims to characterize and minimize risks in accordance with regulatory guidelines.
Again, each drug product is unique. Therefore, parts of the guidelines are applicable to some drug products and not to others. Everything does not apply to every product.
Chemical and pharmaceutical quality — Always important but often overlooked
During development, quality demands may differ from study to study. However, your drug substance and product must always be adequately characterized when it comes to purity, stability, and manufacturing processes. If not, patient safety could be compromised. As a result, regulatory authorities will have no confidence in the results obtained throughout the drug development process.
Establishing a thorough understanding of your molecule and drug product is critical. Not doing so is a common reason for increased costs and time delays in your project.
Nonclinical studies — Understanding your drug and its safety is crucial
Nonclinical studies should support a safe starting dose in humans and identify safety parameters for clinical monitoring. For any new drug product, it is therefore necessary to characterize:
Pharmacology — what the drug does to the body
Primary pharmacodynamics: mode of action and desired effect
Secondary pharmacodynamics: mode of action and undesired effect
Pharmacokinetics — what the body does to the drug
Toxicology — adverse effects
The above aspects are evaluated using standard in vitro assays, such as molecular target(s) profiling, metabolite identification, acute cardiotoxicity, and mutagenic potential. Further, in vivo studies in relevant animal species are also necessary. These animal species should preferably have the same pharmacological targets as in humans. This establishes the drug product’s mechanism-of-action, toxicology, and pharmacokinetic profile.
Design of the first-in-human clinical study
A first-in-human clinical study is designed to evaluate the safety and tolerability of a drug by administering it at ascending doses. However, there are no general answers about an optimal study design. This is because each drug project is different, and every study must be tailored given the indication, mechanisms of action, safety profile, and pharmacokinetics. For instance:
What is an optimal starting dose, dose escalation program, and stopping criteria?
Should the study be performed in healthy volunteers or in a patient population?
Should a placebo be used?
Can multiple study endpoints be incorporated to avoid future complementary clinical evaluations?
Should any specific safety assessments be included?
We need to answer these questions before venturing into clinical trials. However, before they can be asked, a range of unknowns must be characterized and better understood. Therefore, it is important to not only have a thorough understanding of what needs to be done, but, also, executing it specifically for your drug project.
Interested in learning more? Bodil recently presented “The Road to First-in-Human Trials: Insights from a Real-World Example.” Click below to watch the webinar:
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