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

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.

Study Overview

• Status: Completed
• Conditions: Deep Venous Thrombosis
• Intervention / Treatment: Drug: Idrabiotaparinux sodium; Drug: Avidin; Drug: Placebo (for Avidin); Drug: Idraparinux sodium

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 Type: Interventional
• Enrollment (Actual): 757
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1642
    • Sanofi-Aventis
• Australia
  • Macquarie Park, Australia, NSW 2113
    • Sanofi-Aventis
• Austria
  • Vienna, Austria, 1220
    • Sanofi-Aventis
• Belgium
  • Diegem, Belgium, 1831
    • Sanofi-Aventis
• Brazil
  • Sao Paulo, Brazil, 05677-000
    • Sanofi-Aventis
• Canada
  • Laval, Canada, H7L 4A8
    • Sanofi-Aventis
• Czech Republic
  • Praha, Czech Republic, 160 00
    • Sanofi-Aventis
• Denmark
  • Copenhagen, Denmark
    • Sanofi-Aventis
• France
  • Paris, France
    • Sanofi-Aventis France
• Israel
  • Natanya, Israel
    • sanofi-aventis Israel
• Italy
  • Milan, Italy
    • Sanofi-Aventis
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Mexico
• Netherlands
  • Gouda, Netherlands
    • sanofi-aventis, Netherlands
• New Zealand
  • New Zealand, New Zealand
    • Sanofi-Aventis
• Poland
  • Warsawa, Poland, 02-672
    • Sanofi-Aventis
• Russian Federation
  • Moscow, Russian Federation, 103045
    • Sanofi-Aventis
• South Africa
  • Midrand, South Africa, 1685
    • Sanofi-Aventis
• Spain
  • Barcelona, Spain, 08019
    • Sanofi-Aventis
• Turkey
  • Istanbul, Turkey
    • Sanofi-aventis Turkey
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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: Placebo (for Avidin); Avidin matching powder in 10 mg/mL solution Intravenous infusion for 30 minutes; Drug: Idraparinux sodium; 0.5 mL pre-filled syringe for 2.5 mg Subcutaneous injection; Other Names: SR34006

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: April 4, 2006
• First Submitted That Met QC Criteria: April 4, 2006
• First Posted (Estimate): April 5, 2006

Study Record Updates

• Last Update Posted (Estimate): March 21, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Deep Venous Thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Idraparinux; Idrabiotaparinux
• Other Study ID Numbers: EFC5945; 2005-005326-30 (EudraCT Number)