From adults to children: simulation-based choice of an appropriate sparse-sampling schedule

Area of Science:

• Pharmacokinetics
• Pediatric Drug Development
• Clinical Trial Simulation

Background:

• Pharmacokinetic (PK) bridging studies support pediatric drug development per ICH E11 guidelines.
• Optimizing sampling schedules is crucial for PK studies in pediatric populations to minimize blood draws.

Purpose of the Study:

• To utilize clinical trial simulations (CTS) based on adult data for selecting an optimal sparse-sampling schedule for pediatric population PK (popPK) studies.
• To ensure the selected schedule meets predefined acceptance criteria for future pediatric studies.

Main Methods:

• Developed a population PK (popPK) model for gadobutrol using adult Phase I data.
• Employed non-linear mixed-effects modeling for PK analysis and simulations.
• Used CTS to identify the most suitable sparse-sampling schedule for pediatric studies.

Main Results:

• An efficient sampling schedule requiring only three blood samples per patient was successfully identified and implemented.
• The selected schedule was applied in a pediatric Phase I/III clinical study for gadobutrol.
• Population PK analysis determined individual PK parameters in the pediatric study cohort.

Conclusions:

• A priori simulation-based evaluation of sampling schedules using adult data is an effective strategy for planning pediatric studies.
• This method facilitates efficient and minimally invasive PK data collection in pediatric populations.