Population Pharmacokinetic and Pharmacodynamic Modeling of Romiplostim Biosimilar GP40141 and Reference Product in Healthy Volunteers to Evaluate Biosimilarity

Population Pharmacokinetic and Pharmacodynamic Modeling of Romiplostim Biosimilar GP40141 and Reference Product in Healthy Volunteers to Evaluate Biosimilarity

GP40141 is a romiplostim biosimilar. A Phase 1 clinical trial was previously conducted in healthy volunteers to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of GP40141 compared to the reference romiplostim (NCT05652595). Using noncompartmental analysis, the biosimilarity of...

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Published in:Clinical pharmacology in drug development Vol. 13; no. 4; pp. 419 - 431
Main Authors: Makarenko, Igor, Petrov, Aleksandr, Belova, Bella, Saparova, Valeria, Arefeva, Anna, Peskov, Kirill, Kudryashova, Nataliya, Khokhlov, Alexandr, Drai, Roman
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-04-2024
Subjects:
Biological products
biosimilar
Biosimilar Pharmaceuticals - pharmacokinetics
Clinical trials
Healthy Volunteers
Humans
immune thrombocytopenia
MIDD
pharmacodynamics
population pharmacokinetics
Receptors, Fc
Recombinant Fusion Proteins
romiplostim
Thrombopoietin
MIDD
romiplostim
immune thrombocytopenia
pharmacodynamics
biosimilar
population pharmacokinetics
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Summary:GP40141 is a romiplostim biosimilar. A Phase 1 clinical trial was previously conducted in healthy volunteers to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of GP40141 compared to the reference romiplostim (NCT05652595). Using noncompartmental analysis, the biosimilarity of PD end points was determined according to the classical criterion (0.8‐1.25). PK end points were also in good agreement between GP40141 and the reference romiplostim; however, the confidence interval for the area under concentration‐time curve from time 0 to the time of last measurement was slightly out of the bioequivalence range (0.91‐1.29). Population PK/PD was used in the present study to characterize the individual PK and PD data of 56 healthy subjects in 2 cross‐over periods of the Phase 1 clinical trial. Body weight and neutralizing antibodies to romiplostim were found to be important predictors of apparent volume of distribution and linear elimination constant, respectively. Within the framework of the conducted modeling, population estimates of PK/PD parameters were obtained, which were in agreement with literature data for the reference romiplostim. Additionally, values of intersubject variability, previously unreported for romiplostim in a healthy subject population, were derived. Covariate analysis, conducted during model development, as well as visual diagnostics and model‐based simulations, demonstrated the absence of significant differences in PK and PD between GP40141 and romiplostim‐ref.
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ISSN:2160-763X
2160-7648
DOI:10.1002/cpdd.1367