Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX.
(2012) In Journal of Thrombosis and Haemostasis 10(11). p.2305-2312- Abstract
- Background: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (rFIX) molecule with a prolonged half-life. Objectives: To provide information on potential dose regimens for N9-GP for phase 3 pivotal and surgery trials. Methods: A population pharmacokinetic model was developed from single-dose data derived from the first human dose trial with N9-GP in hemophilia B patients, and was used to extrapolate to steady-state conditions for different N9-GP dose regimens for prophylaxis. The model was also used to compare prophylaxis using N9-GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40 IU/kg every third day). Plasma activity following dosing with N9-GP, rFIX, and pdFIX for surgery and on-demand... (More)
- Background: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (rFIX) molecule with a prolonged half-life. Objectives: To provide information on potential dose regimens for N9-GP for phase 3 pivotal and surgery trials. Methods: A population pharmacokinetic model was developed from single-dose data derived from the first human dose trial with N9-GP in hemophilia B patients, and was used to extrapolate to steady-state conditions for different N9-GP dose regimens for prophylaxis. The model was also used to compare prophylaxis using N9-GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40 IU/kg every third day). Plasma activity following dosing with N9-GP, rFIX, and pdFIX for surgery and on-demand treatment of bleeds was also simulated. Results: A linear two-compartmental model best described the pharmacokinetic profiles of N9-GP, rFIX, and pdFIX. A prophylactic regimen of 10 U/kg N9-GP once weekly predicted mean peak and trough levels of 18 and 4.2 U/dL, while 40 U/kg once weekly predicted values of 72 and 17 U/dL, respectively. Standard prophylactic regimens with rFIX and pdFIX predicted mean peak and trough levels of 34 and 3.9 IU/dL for rFIX, and mean values of 43 and 2.1 IU/dL for pdFIX. Additional simulations predicted significantly reduced dosing frequency and factor concentrate consumption for N9-GP versus rFIX and pdFIX for surgery and the treatment of bleeds. Conclusions: N9-GP may allow prophylaxis, surgical dosing regimens, and on-demand treatment of bleeding episodes with less frequent injections and lower factor concentrate consumption; this possibility is being investigated in prospective clinical trials. © 2012 International Society on Thrombosis and Haemostasis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3123802
- author
- Collins, P W ; Møss, J ; Knobe, Karin LU ; Groth, A ; Colberg, T and Watson, E
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Thrombosis and Haemostasis
- volume
- 10
- issue
- 11
- pages
- 2305 - 2312
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000310548400012
- pmid:22998153
- scopus:84868152441
- pmid:22998153
- ISSN
- 1538-7933
- DOI
- 10.1111/jth.12000
- language
- English
- LU publication?
- yes
- id
- 1658a391-8f9d-4a64-bb9e-e44b703a22bb (old id 3123802)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22998153?dopt=Abstract
- date added to LUP
- 2016-04-04 07:34:46
- date last changed
- 2022-01-29 02:22:00
@article{1658a391-8f9d-4a64-bb9e-e44b703a22bb, abstract = {{Background: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (rFIX) molecule with a prolonged half-life. Objectives: To provide information on potential dose regimens for N9-GP for phase 3 pivotal and surgery trials. Methods: A population pharmacokinetic model was developed from single-dose data derived from the first human dose trial with N9-GP in hemophilia B patients, and was used to extrapolate to steady-state conditions for different N9-GP dose regimens for prophylaxis. The model was also used to compare prophylaxis using N9-GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40 IU/kg every third day). Plasma activity following dosing with N9-GP, rFIX, and pdFIX for surgery and on-demand treatment of bleeds was also simulated. Results: A linear two-compartmental model best described the pharmacokinetic profiles of N9-GP, rFIX, and pdFIX. A prophylactic regimen of 10 U/kg N9-GP once weekly predicted mean peak and trough levels of 18 and 4.2 U/dL, while 40 U/kg once weekly predicted values of 72 and 17 U/dL, respectively. Standard prophylactic regimens with rFIX and pdFIX predicted mean peak and trough levels of 34 and 3.9 IU/dL for rFIX, and mean values of 43 and 2.1 IU/dL for pdFIX. Additional simulations predicted significantly reduced dosing frequency and factor concentrate consumption for N9-GP versus rFIX and pdFIX for surgery and the treatment of bleeds. Conclusions: N9-GP may allow prophylaxis, surgical dosing regimens, and on-demand treatment of bleeding episodes with less frequent injections and lower factor concentrate consumption; this possibility is being investigated in prospective clinical trials. © 2012 International Society on Thrombosis and Haemostasis.}}, author = {{Collins, P W and Møss, J and Knobe, Karin and Groth, A and Colberg, T and Watson, E}}, issn = {{1538-7933}}, language = {{eng}}, number = {{11}}, pages = {{2305--2312}}, publisher = {{Wiley-Blackwell}}, series = {{Journal of Thrombosis and Haemostasis}}, title = {{Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX.}}, url = {{http://dx.doi.org/10.1111/jth.12000}}, doi = {{10.1111/jth.12000}}, volume = {{10}}, year = {{2012}}, }