Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX.

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Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. / Collins, P W; Møss, J; Knobe, Karin; Groth, A; Colberg, T; Watson, E.

I: Journal of Thrombosis and Haemostasis, Vol. 10, Nr. 11, 2012, s. 2305-2312.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Collins, P W ; Møss, J ; Knobe, Karin ; Groth, A ; Colberg, T ; Watson, E. / Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. I: Journal of Thrombosis and Haemostasis. 2012 ; Vol. 10, Nr. 11. s. 2305-2312.

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TY - JOUR

T1 - Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX.

AU - Collins, P W

AU - Møss, J

AU - Knobe, Karin

AU - Groth, A

AU - Colberg, T

AU - Watson, E

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1111/jth.12000

DO - 10.1111/jth.12000

M3 - Article

VL - 10

SP - 2305

EP - 2312

JO - Journal of Thrombosis and Haemostasis

T2 - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 11

ER -