Objective
One of the key objectives of ethnic sensitivity study (ESS) is to characterize PK of investigational drugs in different ethnic groups, and to identify potential ethnic difference. Data from the ESS can enhance appropriate dose selection in patients with different ethnicities.
Considering the study objective, it is important to ensure that the study is powered to estimate PK parameters with good precision and to allow ethnic PK comparison. On the other hand, given the cost and feasibility of the study, and subject burden, it is preferable to minimize sample size and sampling schedule.
CTS using population PK (popPK) model allows to evaluate the precision of PK parameter estimates under various trial design settings. Thus, it is a useful approach to assess ESS designs and the ability to adequately characterize PK.
This work aims to quantify the effect of study designs on the precision and accuracy of PK parameter estimates to inform an optimal ESS design by CTS.
Method
PK was described by a two compartment model with first order elimination and absorption modelled with transit compartments.The model structure and parameters were estimated using clinical data from a dose escalation study.
For each ESS design option (sample size, sampling scheme), 1000 trials were simulated by sampling 1000 parameter sets. Individual PK profiles were simulated based on population parameters, between subject variability and residual unexplained variability.
Cmax and AUC were estimated by NCA for each of the simulated individual PK profile. For each trial, precision and accuracy of parameters were calculated.
Result/conclusion
Results show how sample size and sampling schedule affect the precision and accuracy of parameter estimates, which enabled us to identify the suitable study design to achieve the objective of our ESS. The findings highlight that CTS can effectively inform study design to obtain reliable PK parameters, by leveraging the available PK knowledge from previous studies.