ClinicalTrials.gov Identifier: Substudy of NCT00311090 (EQUINOX trial).
Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis
Article first published online: 8 APR 2013
© 2012 Sanofi R&D. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 75, Issue 5, pages 1255–1264, May 2013
How to Cite
Trellu, M., Fau, J.-B., Cortez, P., Cheng, S., Paty, I., Boëlle, E., Donat, F. and Sanderink, G.-J. (2013), Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis. British Journal of Clinical Pharmacology, 75: 1255–1264. doi: 10.1111/bcp.12009
- Issue published online: 8 APR 2013
- Article first published online: 8 APR 2013
- Accepted manuscript online: 19 OCT 2012 02:01AM EST
- Manuscript Accepted: 9 OCT 2012
- Manuscript Received: 20 SEP 2011
- deep vein thrombosis;
To assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg).
In a phase I study, 48 healthy male volunteers were randomized to a single subcutaneous injection of idrabiotaparinux or idraparinux, followed by plasma sampling over 27 days. In a prospective substudy of the phase III EQUINOX trial, 228 patients treated for acute symptomatic deep vein thrombosis received idrabiotaparinux or idraparinux once weekly for 6 months. Plasma sampling was performed within 5 days following the last injection. The primary pharmacodynamic endpoint was the inhibition of activated factor X (FXa) activity. Maximal anti-FXa activity (Amax) and area under anti-FXa activity vs. time curve (AAUC) were calculated. Safety and tolerability were also assessed.
In both studies, pharmacodynamic anti-FXa vs. time profiles of idrabiotaparinux and idraparinux were superimposable. Ratio estimates (90% confidence intervals [CIs]) for idrabiotaparinux : idraparinux were 0.96 (0.89, 1.04) for Amax and 0.95 (0.87, 1.04) for AAUC in the phase I study, and 1.11 (1.00, 1.22) for Amax and 1.06 (0.96, 1.16) for AAUC at month 6 in the EQUINOX substudy. Idrabiotaparinux and idraparinux were considered bioequipotent because 90% CIs were within the pre-specified interval (0.80, 1.25). Study treatments were well tolerated.
Pharmacodynamic parameters reported after single dose in healthy volunteers and after repeated once weekly dosing in patients demonstrated the bioequipotency of idrabiotaparinux and idraparinux based on FXa inhibition. These outcomes support the use of an idrabiotaparinux dose bioequipotent to an idraparinux dose in large clinical trials, and the possibility to substitute idrabiotaparinux to idraparinux for the treatment of venous thromboembolism.