The first time a new compound is administered to human subjects is always an important milestone. In order to design a study that is both safe and informative, the researcher must have a clear overview of all of the preclinical data. This body of data is usually compiled in the investigator’s brochure (IB), a massive document often hundreds of pages long. To help the researcher extract the key data from the IB, CHDR developed the IB-Derisk analyser.
Safe and informative
Having a thorough understanding of the IB’s contents is essential in order to maximise the safety of the volunteers who will be the first subjects to receive the new drug. In particular, unexpected events in preclinical studies and/or differences in species’ response to the test compound can be warning signs of possible complications in early clinical studies. Preclinical data are also needed in order to determine which tests and measurements should be performed in the early clinical studies, as well as the initial dose, dosing range, and route of administration. These tests can also be valuable for indicating which methods can provide key information regarding pharmacology and the putative drug-target interaction. Often, intended and/or unintended effects can be studied in healthy volunteers by using drug-sensitive tests, sophisticated challenge models, ex vivo studies, and other approaches. To maximise safety and design the most informative early clinical studies, investigators must use the wealth of preclinical data to generate predictions regarding the test compound’s pharmacokinetics and pharmacodynamics in human subjects. Thanks to CHDR’s new IB-Derisk analyser, this process is now much simpler.
Cmax and colour codes
To organise all of the preclinical data contained in the IB and reduce the risk of overlooking important results, CHDR’s IB-Derisk tool arranges all preclinical experiments in a convenient table according to the maximal concentration (Cmax) achieved after administration of a single weight-corrected dose. For most species used in preclinical research, Cmax is determined from pharmacokinetics experiments. The Cmax value is then used to rank all of the findings with respect to pharmacological effects in various species. The outcomes are then colour-coded, providing a visual overview of the compound’s intended and/or unintended effects. These colour codes provide additional structure and can help reveal irregularities. Importantly, this visualisation also helps the investigator detect possible risks that might otherwise go unnoticed in the IB.
At CHDR, we have been working with this approach for years. Of course, this approach may not necessarily predict all possible issues that can arise in early drug development, nor should it replace a thorough review of the preclinical information. However, it provides a practical method for organising all of the information contained in the IB and helping reveal irregularities in the preclinical data.