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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1937152
- author
- 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}},
}