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Evaluation of the immunogenicity of the dabigatran reversal agent idarucizumab during Phase I studies
- Source :
- British Journal of Clinical Pharmacology. 83:1815-1825
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Aims Idarucizumab, a humanized monoclonal anti-dabigatran antibody fragment, is effective in emergency reversal of dabigatran anticoagulation. Pre-existing and treatment-emergent anti-idarucizumab antibodies (antidrug antibodies; ADA) may affect the safety and efficacy of idarucizumab. This analysis characterized the pre-existing and treatment-emergent ADA and assessed their impact on the pharmacokinetics and pharmacodynamics (PK/PD) of idarucizumab. Methods Data were pooled from three Phase I, randomized, double-blind idarucizumab studies in healthy Caucasian subjects; elderly, renally impaired subjects; and healthy Japanese subjects. In plasma sampled before and after idarucizumab dosing, ADA were detected and titrated using a validated electrochemiluminescence method. ADA epitope specificities were examined using idarucizumab and two structurally related molecules. Idarucizumab PK/PD data were compared for subjects with and without pre-existing ADA. Results Pre-existing ADA were found in 33 out of 283 individuals (11.7%), seven of whom had intermittent ADA. Titres of pre-existing and treatment-emergent ADA were low, estimated equivalent to
- Subjects :
- 0301 basic medicine
Pharmacology
business.industry
Immunogenicity
Idarucizumab
030204 cardiovascular system & hematology
Placebo
Dabigatran
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Pharmacokinetics
Monoclonal
medicine
Pharmacology (medical)
Dosing
Adverse effect
business
medicine.drug
Subjects
Details
- ISSN :
- 03065251
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- British Journal of Clinical Pharmacology
- Accession number :
- edsair.doi...........e0a19804bbad6d698183eea75b574082