PK/PD Evaluation
Pharmacokinetics and/or pharmacodynamics evaluation was required in all
WRs and listed as primary endpoint in 18 pediatric studies. In all
competed or ongoing studies in response to the WRs, PK samples were
collected through rich or sparse sampling to be analyzed with Population
PK analysis and/or noncompartmental PK analysis. Key PK parameters (AUC,
Cmax, Clearance, and volume of distribution, etc) were obtained.
Depending on the planned age range for each study, PK collection was
required from a minimum of 6-10 patients in each of the following age
groups: 1 month to < 2 years or 12 months to < 6
years, 6 to < 12 years, and 12 to <18 years of age.
Using combined data from available studies, Population PK/PD modeling
and/or exposure-response analysis for safety and efficacy were conducted
or planned to determine the optimal dose in the target pediatric
population. In recent WRs for large molecules, characterization of
immunogenicity was also required.