Pharmacokinetics of a novel extended half-life glycoPEGylated factor IX, nonacog beta pegol (N9-GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials.
Haemophilia
; 23(4): 547-555, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-28233381
ABSTRACT
INTRODUCTION:
Nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (FIX) with an extended half-life developed for routine prophylaxis and the prevention and treatment of bleeding episodes in patients with haemophilia B.AIM:
The aim of this study was to evaluate the pharmacokinetics (PK) of N9-GP.METHODS:
Data from 41 previously treated haemophilia B patients, enrolled globally (16 adolescents/adults and 25 children; FIX activity ≤0.02 IU mL-1 ) with no history of FIX inhibitors, were included. N9-GP was administered once-weekly as 10 IU kg-1 or 40 IU kg-1 in adolescents/adults and 40 IU kg-1 in children. Blood was sampled up to 168 h (1 week) post dose. Standard PK was estimated on the basis of plasma FIX activity vs. time (PK profiles) using non-compartmental methods. Furthermore, a population PK analysis and FIX activity predictions were performed.RESULTS:
Incremental recoveries were 0.02 (IU mL-1 )/(IU kg-1 ) in both adolescents/adults and children. The extended half-life resulted in mean trough levels of 0.27 IU mL-1 for adolescents/adults and 0.17 IU mL-1 for children at steady-state after weekly dosing at 40 IU kg-1 . The population PK analysis confirmed a mono-exponential decay in FIX activity and allowed for predictions of FIX activity for adolescents/adults above 0.15 IU mL-1 at all times and 6.4 days week-1 in children.CONCLUSION:
N9-GP has the potential to shift previously treated haemophilia B patients from a severe/moderate disease state into a mild- or non-haemophilic range for most of the dosing interval, which is expected to reduce the number of bleeding episodes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Factor IX
/
Hemofilia B
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Child
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Child, preschool
/
Humans
/
Male
Idioma:
En
Revista:
Haemophilia
Asunto de la revista:
HEMATOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania