Bioequipotency Study of Idrabiotaparinux and Idraparinux in Patients With Deep Venous Thrombosis of the Lower Limbs (EQUINOX)

Bioequipotency Study of Idrabiotaparinux and Idraparinux in Patients With Deep Venous Thrombosis of the Lower Limbs

International, Multicenter, Randomized, Parallel Group, Double-blind Study, in Patients With Acute Symptomatic Deep Vein Thrombosis of the Lower Limbs, Demonstrating the Bioequipotency at Steady State of Equimolar Doses of SSR126517E (3.0 mg) Once a Week and SR34006 (2.5 mg) Once a Week, Documenting the Safety and Efficacy of Both Compounds During a 6-month Treatment, and Demonstrating the Neutralizing Effect of SSR29261 on the SSR126517E-induced Anti-Xa Activity

The three purposes of this study are the following: To compare during a 6-month treatment the safety and effectiveness of idrabiotaparinux (SSR126517) with that of idraparinux (SR34006), taking into account new events of deep venous thrombosis (DVT) and pulmonary embolism (PE), and bleeding risk; To compare the activities of idrabiotaparinux and idraparinux directly in blood during and after a 6-month treatment; To check the ability of avidin (SSR29261) to reverse the blood thinning activity of idrabiotaparinux at the end of a 6-month treatment period.

The study consists in a 6-month treatment period followed by an observational period of 3 to 6 months with a month 9 visit and a phone/contact visit at month 12. All participants who complete the 6-month treatment period are re-randomized to either the idrabiotaparinux/idraparinux bioequipotency sub-study or the avidin neutralizing effect sub-study.

Idrabiotaparinux sodium , 3.0 mg, once-weekly for 6 months. In avidin sub-study, participants receive on Day 183, avidin 100 mg or placebo (for avidin) (4 hours after Idrabiotaparinux administration)

Idraparinux sodium, 2.5 mg, once-weekly for 6 months In avidin sub-study, participants receive on Day 183, placebo (for avidin) (4 hours after Idrabiotaparinux administration)

Avidin neutralizing effect substudy: decrease in anti-Xa activity between the start and end of the avidin infusion

Safety: number of participants with clinically relevant bleedings and number of deaths as confirmed by a Central Independent Adjudication Committee (CIAC)

Efficacy: number of participants with symptomatic recurrent venous thromboembolism as confirmed by the CIAC

Inclusion Criteria: Confirmed acute symptomatic DVT of the lower limbs Exclusion Criteria: Severe concomitant diseases (e.g. renal failure, hepatic failure, uncontrolled hypertension) Active bleeding or high risk for bleeding. Pregnancy or childbearing potential without proper contraceptive measures. Breastfeeding Known allergy to idraparinux, SSR126517E, or egg proteins Indication of prolonged anticoagulation for other reason than DVT of the lower limbs Symptomatic pulmonary embolism (PE) Life expectancy < 6 months.

Equinox Investigators. Efficacy and safety of once weekly subcutaneous idrabiotaparinux in the treatment of patients with symptomatic deep venous thrombosis. J Thromb Haemost. 2011 Jan;9(1):92-9. doi: 10.1111/j.1538-7836.2010.04100.x.

Trellu M, Fau JB, Cortez P, Cheng S, Paty I, Boelle E, Donat F, Sanderink GJ. Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis. Br J Clin Pharmacol. 2013 May;75(5):1255-64. doi: 10.1111/bcp.12009.

Paty I, Trellu M, Destors JM, Cortez P, Boelle E, Sanderink G. Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion. J Thromb Haemost. 2010 Apr;8(4):722-9. doi: 10.1111/j.1538-7836.2010.03746.x. Epub 2010 Jan 17.