Multiple Ascending Dose Studies

Overview of Multiple Ascending Dose (MAD) Studies

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.

Nuventra Services Provided for these Types of Studies

  • Full clinical protocol development from clinical pharmacology experts
  • Clinical trial design
  • PK sampling schedule evaluation
  • Interim pharmacokinetic evaluation between dose escalation cohorts
  • Topline assessment of food effect within 24 hours
  • Full PK analysis (PK parameters) conducted in WinNonlin
  • Full or abbreviated PK report
  • Clinical study reports (CSRs) – with integrated PK data
  • Investigator Brochure (IB) updates to clinical pharmacology and PK data
  • FDA meetings or EMA meetings: Expert clinical pharmacology representation at regulatory meetings (including Briefing packet preparation)
  • Interpretation of PK data to enable next steps in the development program
    • Incorporation of data into model based drug development to allow for better decision making.
    • Impact of study results on other planned clinical studies
  • Although Nuventra does not enroll or dose subjects in clinical trials, our high level of experience with designing, executing and analyzing data from clinical pharmacology & PK/PD studies makes us the best option for clients needing advice in this area of drug development.

 

Brief Scientific & PK Considerations for these Studies

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.

Let Nuventra’s clinical pharmacology consultants, pharmacokineticists, and drug development experts help intelligently integrate this study into your overall develpment efforts. Click here for a free Clinical Pharmacology Plan.

Contact us or request a quote to help with your drug development needs for this type of clinical pharmacology investigation.