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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Deep Venous Thrombosis

Intervention / Treatment
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* Drug: Idrabiotaparinux sodium
* Drug: Idraparinux sodium
* Drug: Avidin
* Drug: Placebo (for Avidin)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idrabiotaparinux<br>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) | Drug: Idrabiotaparinux sodium<br>* 0.5 mL pre-filled syringe for 3.0 mg Subcutaneous injection<br>* Other names: SSR126517;Drug: Avidin<br>* 100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes<br>* Other names: SSR29261;Drug: Placebo (for Avidin)<br>* Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes<br>|
| Active Comparator: Idraparinux<br>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) | Drug: Idraparinux sodium<br>* 0.5 mL pre-filled syringe for 2.5 mg Subcutaneous injection<br>* Other names: SR34006;Drug: Placebo (for Avidin)<br>* Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequipotency sub-study: idrabiotaparinux/idraparinux ratio for pharmacodynamic exposure parameters |  | Day 183 | 
| Avidin neutralizing effect substudy: decrease in anti-Xa activity between the start and end of the avidin infusion |  | Day 183 to Day 188 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile: idrabiotaparinux and idraparinux plasma concentrations |  | Days 15, 36, 57, 92 and 183 | 
| Safety: number of participants with clinically relevant bleedings and number of deaths as confirmed by a Central Independent Adjudication Committee (CIAC) |  | First 6 months | 
| Efficacy: number of participants with symptomatic recurrent venous thromboembolism as confirmed by the CIAC |  | First 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Venous Thrombosis