RESUMEN
A novel formulation of C1 esterase inhibitor concentrate, a plasma product used in the treatment of hereditary angioedema (HAE), was studied in a clinical trial for similarity in pharmacokinetics (PK) compared with the reference product. Direct trial data were limited given the availability of patients, and therefore a modeling approach was used to study similarity. Type I error of the study was evaluated using simulations based on retrospective data. A population PK modeling analysis was performed on data from the trial. Analysis of variance was carried out on results of a noncompartmental PK analysis (NCA) of the clinical data. Simulations showed that type I error was inflated to 62% (P < .05) when bioequivalence criteria (confidence intervals within 80%-125%) were adhered to strictly. In the clinical trial, 13 HAE patients were evaluable. The population PK analysis showed no significant differences in PK parameters, whereas confidence intervals for all parameters were within 80% to 125%. The relative differences in area under the curve, incremental recovery, and mean residence time estimated using NCA were all close to 1. The novel formulation showed similar PK characteristics to the original formulation. The model-based approach showed that strict criteria for PK comparison could not be applied in this analysis.