Safety and pharmacokinetics of subcutaneously administered recombinant activated factor VII (rFVIIa).
(2011) In Journal of Thrombosis and Haemostasis 9. p.1191-1199- Abstract
- Background: Recombinant factor VIIa (rFVIIa) is used to treat bleeds in hemophilia patients with inhibitors. A subcutaneous formulation could potentially improve its half-life and make it suitable for prophylactic treatment. Objectives: A study was conducted to determine the safety of subcutaneously administered rFVIIa in patients with hemophilia and the pharmacokinetic profile (including bioavailability). Patients/Methods: This was a multi-center, open-label, cross-over comparison of single doses of intravenous rFVIIa 90 μg/kg and a new formulation of rFVIIa for subcutaneous injection at dose levels of 45, 90, 180, 270 and 360 μg/kg. Sixty subjects (12 per dose cohort) with hemophilia A or B were enrolled. Results: Subcutaneously... (More)
- Background: Recombinant factor VIIa (rFVIIa) is used to treat bleeds in hemophilia patients with inhibitors. A subcutaneous formulation could potentially improve its half-life and make it suitable for prophylactic treatment. Objectives: A study was conducted to determine the safety of subcutaneously administered rFVIIa in patients with hemophilia and the pharmacokinetic profile (including bioavailability). Patients/Methods: This was a multi-center, open-label, cross-over comparison of single doses of intravenous rFVIIa 90 μg/kg and a new formulation of rFVIIa for subcutaneous injection at dose levels of 45, 90, 180, 270 and 360 μg/kg. Sixty subjects (12 per dose cohort) with hemophilia A or B were enrolled. Results: Subcutaneously administered rFVIIa showed lower mean peak plasma concentrations and prolonged FVII activity (C(max) :0.44-5.16 IU/mL [across doses], t(1/2) :12.4 hours, t(max) :5.6 hours) compared with intravenously administered rFVIIa (C(max) :51.7 IU/mL, t(1/2) :2.7 hours, t(max) :<10 minutes). The absolute bioavailability of subcutaneous rFVIIa ranged from 21.1%-30.1% across dose levels. Dose proportionality was observed within a 2-fold dose increase but not across the full dose range. No thromboembolic events, drug-related serious adverse events, severe injection-site reactions or neutralizing antibodies were reported (primary endpoint). Mild and moderate injection-site reactions were more frequent with subcutaneous than with intravenous injections. Conclusion: This phase I clinical trial did not identify safety concerns of prolonged exposure to rFVIIa administered subcutaneously in single doses to hemophilia patients. (Less)
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https://lup.lub.lu.se/record/1937152
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- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Thrombosis and Haemostasis
- volume
- 9
- pages
- 1191 - 1199
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000291315600014
- pmid:21489128
- scopus:79958065035
- pmid:21489128
- ISSN
- 1538-7933
- DOI
- 10.1111/j.1538-7836.2011.04293.x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical Coagulation Research Unit (013242510), Emergency medicine/Medicine/Surgery (013240200), Division of Microbiology, Immunology and Glycobiology - MIG (013025200)
- id
- f357245d-851c-48de-889d-4aaaac51efa8 (old id 1937152)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21489128?dopt=Abstract
- date added to LUP
- 2016-04-04 07:53:09
- date last changed
- 2022-05-16 20:30:36
@article{f357245d-851c-48de-889d-4aaaac51efa8, abstract = {{Background: Recombinant factor VIIa (rFVIIa) is used to treat bleeds in hemophilia patients with inhibitors. A subcutaneous formulation could potentially improve its half-life and make it suitable for prophylactic treatment. Objectives: A study was conducted to determine the safety of subcutaneously administered rFVIIa in patients with hemophilia and the pharmacokinetic profile (including bioavailability). Patients/Methods: This was a multi-center, open-label, cross-over comparison of single doses of intravenous rFVIIa 90 μg/kg and a new formulation of rFVIIa for subcutaneous injection at dose levels of 45, 90, 180, 270 and 360 μg/kg. Sixty subjects (12 per dose cohort) with hemophilia A or B were enrolled. Results: Subcutaneously administered rFVIIa showed lower mean peak plasma concentrations and prolonged FVII activity (C(max) :0.44-5.16 IU/mL [across doses], t(1/2) :12.4 hours, t(max) :5.6 hours) compared with intravenously administered rFVIIa (C(max) :51.7 IU/mL, t(1/2) :2.7 hours, t(max) :<10 minutes). The absolute bioavailability of subcutaneous rFVIIa ranged from 21.1%-30.1% across dose levels. Dose proportionality was observed within a 2-fold dose increase but not across the full dose range. No thromboembolic events, drug-related serious adverse events, severe injection-site reactions or neutralizing antibodies were reported (primary endpoint). Mild and moderate injection-site reactions were more frequent with subcutaneous than with intravenous injections. Conclusion: This phase I clinical trial did not identify safety concerns of prolonged exposure to rFVIIa administered subcutaneously in single doses to hemophilia patients.}}, author = {{Tiede, A and Friedrich, Ute and Stenmo, C and Allen, G and Giangrande, P and Goudemand, J and Hay, C and Holmström, Eva M and Klamroth, R and Lethagen, Stefan and McKenzie, S and Miesbach, W and Negrier, C and Yuste, V J and Berntorp, Erik}}, issn = {{1538-7933}}, language = {{eng}}, pages = {{1191--1199}}, publisher = {{Wiley-Blackwell}}, series = {{Journal of Thrombosis and Haemostasis}}, title = {{Safety and pharmacokinetics of subcutaneously administered recombinant activated factor VII (rFVIIa).}}, url = {{http://dx.doi.org/10.1111/j.1538-7836.2011.04293.x}}, doi = {{10.1111/j.1538-7836.2011.04293.x}}, volume = {{9}}, year = {{2011}}, }