Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion.
BACKGROUND
Idraparinux is an inhibitor of activated factor X (FXa) with a long half-life allowing once-weekly dosing. Idrabiotaparinux is a biotinylated version of idraparinux; its activity can be reversed with avidin.


OBJECTIVE
To investigate the tolerability, safety and pharmacodynamics of avidin in healthy subjects and patients with deep vein thrombosis (DVT) receiving idrabiotaparinux.


METHODS
In a placebo-controlled, randomized, double-blind Phase I study, 41 healthy males received subcutaneous idrabiotaparinux before being randomized to a 30-min intravenous avidin infusion or placebo. Idrabiotaparinux plus avidin were re-administered 10-14 months later in eight subjects. In addition, in a prospective substudy of the Phase III EQUINOX trial, 55 patients who received weekly idrabiotaparinux for 6 months were randomized to receive either 100 mg avidin (n = 33) or placebo (n = 22). The primary activity outcome was anti-FXa activity calculated immediately before and after avidin infusion. Adverse events were recorded to assess safety and tolerability.


RESULTS
Avidin rapidly reversed the anti-FXa activity of idrabiotaparinux, ranging from 66.1 to 90.3% in healthy subjects and from 67 to 97% (mean 78%) in DVT patients. Avidin was well tolerated, with a similar nature and frequency of adverse events to placebo. No venous thromboembolism recurrence occurred in the 3-month post-avidin infusion.


CONCLUSIONS
A 30-min intravenous infusion of avidin 100 mg is well tolerated, safe, and offers immediate and specific reversibility both after single and repeated doses of idrabiotaparinux in healthy subjects, and in DVT patients following a 6-month treatment period.
Paty
I
I
Sanofi-aventis Recherche & Développement, Clinical and Pharmacology Department, Chilly-Mazarin, France. isabelle.paty@sanofi-aventis.com
Trellu
M
M
Destors
J-M
JM
Cortez
P
P
Boëlle
E
E
Sanderink
G
G
D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D001360:Avidin / Q000008:administration & dosage* / Q000009:adverse effects; D001710:Biotin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003029:Coagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D009844:Oligosaccharides / Q000008:administration & dosage*; D011446:Prospective Studies; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
D000925:Anticoagulants; D003029:Coagulants; D065427:Factor Xa Inhibitors; D009844:Oligosaccharides; D001360:Avidin; D001710:Biotin; C545956:idrabiotaparinux