10: From Bench to Bedside: The First Studies of a New Molecule in Man

Chemists are involved in much of the work that paves the way for clinical studies of a potential new medicine: synthesis and characterisation of the drug substance, method development, formulation of a medicinal product, and analysis. Chemistry continues to play an important role during the early clinical phases of drug development and beyond: clinical studies may lead to the development of a new drug candidate, guide formulation development, or reveal one or more metabolites, which must be identified and characterised. So, although clinical pharmacology is traditionally the realm of physicians, biologists and biochemists, it is important that medicinal chemists are involved in, and understand, the clinical development of potential new medicines. This chapter describes the chemistry data needed to support “first-in-human” clinical trials. It explains the aims and design of the classical single ascending-dose study, and outlines special considerations for those studies, such as choice of population, starting dose, and dose-escalation strategy. Flexibility of the study design and the ability to work within tight timelines in a highly regulated environment are essential, so the logistical challenges are substantial. The chapter closes with case studies that demonstrate how the value of early clinical studies can be maximised to show proof-of-concept and guide dosing regimens in patients.