Designing and interpreting the results of first-time-to-man studies

First human administration of a new chemical entity (NCE) constitutes a critical step in drug development. The primary objective of such a study is the assessment of the shortterm safety and tolerability of single and multiple doses of the NCE in healthy volunteers. Secondary objectives are to obtain preliminary data on the pharmacokinetics and pharmacodynamics using surrogate or biornarkers of the beneficial as well as the adverse effects of the drug. Interpretation of safety data should be cautious and mainly based on comparisons with placebo. A special focus should be made on the assessment of adverse events, liver enzymes, and cardiac repolarization. Well-designed, first-time-to-man studies should determine the safety of the NCE in humans and predict the dose range that may be used to safely and accurately conduct further clinical trials in the target patient population based on safety data (maximum tolerated dose), pharmacodynamics (minimum active dose, duration of action, and dosage regimen), and pharmacokinetics (dosage regimen).