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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00311090

Collaborator

(none)

757

Enrollment

Locations

Arms

Duration (Months)

37.9

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Deep Venous Thrombosis	Drug: Idrabiotaparinux sodium Drug: Idraparinux sodium Drug: Avidin Drug: Placebo (for Avidin)	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

757 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2006

Actual Primary Completion Date :

Jan 1, 2008

Actual Study Completion Date :

Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Idrabiotaparinux 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 0.5 mL pre-filled syringe for 3.0 mg Subcutaneous injection Other Names: Biotinylated Idraparinux SSR126517 Drug: Avidin 100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes Other Names: SSR29261 Drug: Placebo (for Avidin) Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes
Active Comparator: Idraparinux 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 0.5 mL pre-filled syringe for 2.5 mg Subcutaneous injection Other Names: SR34006 Drug: Placebo (for Avidin) Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes

Arm

Intervention/Treatment

Experimental: Idrabiotaparinux

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

0.5 mL pre-filled syringe for 3.0 mg Subcutaneous injection

Other Names:

Biotinylated Idraparinux

SSR126517

Drug: Avidin

100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes

Other Names:

SSR29261

Drug: Placebo (for Avidin)

Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes

Active Comparator: Idraparinux

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

0.5 mL pre-filled syringe for 2.5 mg Subcutaneous injection

Other Names:

SR34006

Drug: Placebo (for Avidin)

Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis	Bridgewater	New Jersey	United States	08807
2	Sanofi-Aventis	Buenos Aires		Argentina	1642
3	Sanofi-Aventis	Macquarie Park		Australia	NSW 2113
4	Sanofi-Aventis	Vienna		Austria	1220
5	Sanofi-Aventis	Diegem		Belgium	1831
6	Sanofi-Aventis	Sao Paulo		Brazil	05677-000
7	Sanofi-Aventis	Laval		Canada	H7L 4A8
8	Sanofi-Aventis	Praha		Czech Republic	160 00
9	Sanofi-Aventis	Copenhagen		Denmark
10	sanofi-aventis France	Paris		France
11	sanofi-aventis Israel	Natanya		Israel
12	Sanofi-aventis	Milan		Italy
13	sanofi-aventis Mexico	Mexico		Mexico
14	sanofi-aventis, Netherlands	Gouda		Netherlands
15	Sanofi-Aventis	New Zealand		New Zealand
16	Sanofi-Aventis	Warsawa		Poland	02-672
17	Sanofi-aventis	Moscow		Russian Federation	103045
18	Sanofi-Aventis	Midrand		South Africa	1685
19	Sanofi-Aventis	Barcelona		Spain	08019
20	sanofi-aventis Turkey	Istanbul		Turkey