Model development and validation
The study focused on developing an optimally parameterized PK model which can clearly capture the product characteristic as well as describe the observed clinical PK profiles accurately. Various compartmental models and the incorporation of product-specific characteristics such as in-vitro dissolution profiles (Supplementary Fig 1) of the test and reference products were tried iteratively to establish the best fit to the observed pharmacokinetic data.
The developed model was used to simulate the original clinical study of test and reference products in 51 virtual subjects and was assessed for comparability based on average bioequivalence. The confidence intervals of the Geometric mean ratio of Cmax and AUC were derived and these results were compared with the corresponding BE results from observed clinical data for the reference and test product.