Journal article
Development and Validation of a Population-Pharmacokinetic Model for Rurioctacog Alfa Pegol (Adynovate (R)): A Report on Behalf of the WAPPS-Hemo Investigators Ad Hoc Subgroup
Clinical pharmacokinetics, Vol.59(2), pp.245-256
02/01/2020
DOI: 10.1007/s40262-019-00809-6
PMID: 31435896
Abstract
Background and objective Rurioctacog alfa pegol (Adynovate) is a modified recombinant factor VIII concentrate used for treating hemophilia A. Aiming to improve treatment tailoring on the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) platform for patients of all ages treated with Adynovate, we have developed and evaluated a population pharmacokinetic (PopPK) model. On the platform, PopPK models are used as priors for Bayesian forecasting that derive individual PK of hemophilia patients and are subsequently used for personalized dose regimen design. Methods Factor activity measurements and demographic covariate data from patients infused with Adynovate were extracted from the WAPPS-Hemo database. Evaluations testing the appropriateness of Bayesian forecasting included 10-fold cross validation, a limited sampling analysis (LSA), and an external evaluation using additional independent data extracted from the WAPPS-Hemo database at a later date. Results The model was constructed using 650 plasma factor activity observations (555 one stage assay and 95 chromogenic assay - 4.6% below limit of quantification) measured in 154 patients from 36 hemophilia centres. A two-compartment model including between subject variability on clearance and central volume was selected as the base model. Covariates were fat free mass on clearance and central volume, age on clearance and assay type on activity. The final model was well-suited to predict PK parameters of new individuals (n = 26) from sparse observations. Conclusions The development of a PopPK model for Adynovate using real-world data increases the covariate space (e.g. age) beyond what is possible from clinical trial data. This model is available on the WAPPS-Hemo platform for tailoring treatment in hemophilia A patients.
Details
- Title: Subtitle
- Development and Validation of a Population-Pharmacokinetic Model for Rurioctacog Alfa Pegol (Adynovate (R)): A Report on Behalf of the WAPPS-Hemo Investigators Ad Hoc Subgroup
- Creators
- Pierre Chelle - University of WaterlooCindy H. T. Yeung - McMaster UniversityStacy E. Croteau - Boston Children's HospitalJennifer Lissick - Minnesota West Community & Technical CollegeVinod Balasa - Valley Children's Healthcare, Madera, CA, USA.Christina Ashburner - Valley Children's Healthcare, Madera, CA, USA.Young Shil Park - Kyung Hee University Hospital at GangdongSantiago Bonanad - Hospital Universitari i Politècnic La FeJuan Eduardo Megias-Vericat - Hospital Universitari i Politècnic La FeAzusa Nagao - Ogikubo HospitalTung Wynn - University of FloridaFernando Corrales-Medina - University of MiamiHuyen Tran - Ronald Sawers Haemophilia Treatment Centre, Melbourne, VIC, Australia.Anjali Sharathkumar - University of IowaMeera Chitlur - Children's Hospital of MichiganSamuel Sarmiento - Integral ConsultingAndrea Edginton - University of WaterlooAlfonso Iorio - McMaster University
- Resource Type
- Journal article
- Publication Details
- Clinical pharmacokinetics, Vol.59(2), pp.245-256
- Publisher
- Springer Nature
- DOI
- 10.1007/s40262-019-00809-6
- PMID
- 31435896
- ISSN
- 0312-5963
- eISSN
- 1179-1926
- Number of pages
- 12
- Language
- English
- Date published
- 02/01/2020
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984354049502771
Metrics
18 Record Views