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
| Autor: | Elena Santagostino, Manuel Carcao, Wan Hui Ong Clausen, Susan Kearney, Johannes Oldenburg, Guy Young, Andreas Tiede, Tadashi Matsushita, Peter Persson, Claude Negrier, F. Abdul-Karim |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Adolescent Population 030204 cardiovascular system & hematology Haemophilia Hemophilia B Polyethylene Glycols Factor IX 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Humans Tissue Distribution Haemophilia B Dosing Child education Genetics (clinical) education.field_of_study Dose-Response Relationship Drug business.industry Half-life Hematology General Medicine medicine.disease Recombinant Proteins Clinical trial Child Preschool business 030215 immunology medicine.drug |
| Zdroj: | Haemophilia. 23:547-555 |
| ISSN: | 1351-8216 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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