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

• ClinicalTrials.gov Identifier: NCT00311090
• Recruitment Status: Completed
• First Posted: April 5, 2006
• Last Update Posted: March 21, 2016
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: April 4, 2006
• First Posted Date: April 5, 2006
• Last Update Posted Date: March 21, 2016
• Study Start Date: April 2006
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 27, 2013)

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

Original Primary Outcome Measures (submitted: April 4, 2006)

• Bioequipotency assessment and avidin neutralizing effect assessment, at steady state:
• The pharmacodynamic/pharmacokinetic variable is the antithrombotic activity (anti-Xa activity)

Current Secondary Outcome Measures (submitted: November 27, 2013)

• Pharmacokinetic profile: idrabiotaparinux and idraparinux plasma concentrations [ Time Frame: 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) [ Time Frame: First 6 months ]
• Efficacy: number of participants with symptomatic recurrent venous thromboembolism as confirmed by the CIAC [ Time Frame: First 6 months ]

Original Secondary Outcome Measures (submitted: April 4, 2006)

• PK/PD: time course to steady state achievement(anti-Xa activity)
• Safety:bleeding adverse events and deaths within 6 months validated by the Central Independent Adjudication Committee (CIAC).
• Efficacy:symptomatic recurrent DVT/PE (fatal or not) within 6 months validated by the CIAC.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Deep Venous Thrombosis

Intervention

• Drug: Idrabiotaparinux sodium

  0.5 mL pre-filled syringe for 3.0 mg

  Subcutaneous injection

  Other Names:

  • Biotinylated Idraparinux
  • SSR126517
• Drug: Idraparinux sodium

  0.5 mL pre-filled syringe for 2.5 mg

  Subcutaneous injection

  Other Name: SR34006
• Drug: Avidin

  100 mg in 10 mg/mL solution

  Intravenous infusion for 30 minutes

  Other Name: SSR29261
• Drug: Placebo (for Avidin)

  Avidin matching powder in 10 mg/mL solution

  Intravenous infusion for 30 minutes

Study Arms

• 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)

  Interventions:

  • Drug: Idrabiotaparinux sodium
  • Drug: Avidin
  • Drug: Placebo (for Avidin)
• 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)

  Interventions:

  • Drug: Idraparinux sodium
  • Drug: Placebo (for Avidin)

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 12, 2010): 757
• Original Enrollment (submitted: April 4, 2006): 700
• Actual Study Completion Date: January 2008
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Israel, Italy, Mexico, Netherlands, New Zealand, Poland, Russian Federation, South Africa, Spain, Turkey, United States
• Removed Location Countries: Germany, Sweden

Administrative Information

• NCT Number: NCT00311090
• Other Study ID Numbers: EFC5945; 2005-005326-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanofi
• Original Responsible Party: Not Provided
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ICD CSD; Sanofi

• PRS Account: Sanofi
• Verification Date: February 2016