What is Phase I?
Each potential new drug must undergo a period of preclinical testing before it can be given to humans. Traditionally, this has involved toxicology studies in rodent and non-rodent species, broadly to determine the doses associated with toxicity and the targets of that toxicity. The degree to which the toxicity is reversible following removal of the drug may also be assessed. The preclinical studies used to prepare for the administration of biopharmaceutical molecules (e.g. monoclonal antibodies) to man are very different and is usually focused on ensuring an adequate understanding of the biology of the target. The choice of species for preclinical studies must be determined by their similarity to the biology in man. Other preclinical studies are required to evaluate effects on fertility, reproduction, teratogenicity (fetal malformations), mutagenicity (genetic mutation) and carcinogenicity (propensity to cause cancer).
Phase I studies have traditionally been conducted in healthy volunteers (Fig 9) but more and more new drugs are now tested in patients from the outset. Dosing is short term and its primary purpose is to explore the safety, tolerability and pharmacokinetic properties of the new drug. Most trials will also involve some assessment of pharmacodynamic action perhaps by measurement of the effect of the drug on a biomarker (e.g. its effect on cell surface markers of activation).
Fig 9 A Phase I healthy volunteer clinical trials unit.
