Multiple Ascending Dose (MAD) studies are conducted following the completion of a single dose, dose escalation study design (single ascending dose or SAD study). Multiple Ascending Dose human studies are typically conducted in healthy volunteers utilizing a dose escalation study design to identify the drug’s pharmacokinetic behavior at steady state and also to identify the maximum tolerated multiple dose. As with single ascending dose studies, sponsors may include pre-defined clinical stopping criteria in their clinical protocols and conduct interim evaluations of safety data between dose escalation cohorts. Also, Nuventra recommends the evaluation of interim pharmacokinetic data between cohorts in a multiple dose escalation study. This will allow an opportunity to confirm or adjust the pharmacokinetic sampling schedule that was originally based on single dose human data.
Scientific & PK Considerations
Common mistakes in Multiple Ascending Dose studies include not dosing the patients correctly or long enough to allow the attainment of steady state and not having an adequate pharmacokinetic sampling schedule to enable accurate and robust assessment of the steady state pharmacokinetic behavior of investigational drugs.