POPULATION PHARMACOKINETIC ANALYSIS OF IGPRO10 IN JAPANESE PATIENTS WITH PRIMARY IMMUNODEFICIENCY
- Mikhail A. Rojavin, United States of America
Abstract
Background and Aims
We aimed to characterize the pharmacokinetics (PK) of serum immunoglobulin G (IgG) following 3- or 4-weekly administration of IgPro10 (Privigen®, CSL Behring) in Japanese patients with primary immunodeficiencies, and compare with non-Japanese patients. A previously-developed population PK (PPK) model (Landersdorfer CB et al., Postgrad Med 2013;125:53‒61) was validated, and predicted parameters compared with clinical study results.
Methods
The previously-developed PPK model, containing IgG concentration data from 5 non-Japanese studies, was supplemented with data from 3 Japanese studies (IgPro10 or IgPro20 [Hizentra®, CSL Behring]). The model was externally validated by simulating IgG concentration-time profiles in Japanese patients to predict serum IgG PK characteristics and compare with observed Japanese PK data in Study IgPro10_3004 (EudraCT: 2016-001631-12).
Results
The analysis included 4,502 serum IgG concentration values (34 Japanese/168 non-Japanese patients). PPK estimates from the current analysis were consistent with the previously-published PPK model (including clearance [%inter-individual variability, IIV], 0.139 [24%] vs 0.142 L/day; central volume, 4.01 [92.1%] vs 3.94 L, respectively), with similar bootstrap mean and 95% confidence intervals (CI). Prediction-corrected visual predictive checks confirmed a good description of data for SCIG and IVIG. PK parameters were equivalent between Japanese/non-Japanese patients. Simulated and observed area under concentration-time curve, and maximum and minimum serum IgG concentrations were similar (Figure), with 90% CI overlapping between simulated and observed values.
Conclusions
PK parameter estimates of serum IgG were similar between Japanese and non-Japanese patients. The PPK model, updated with Japanese data, could accurately predict both individual and population serum IgG concentration-time profiles following 3-weekly and 4-weekly IgPro10.