Rivaroxaban for Treatment in Venous or Arterial Thrombosis in Neonates

NCT02564718 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 176182014-002385-74
• Study Type: interventional
• Target: 10
• Locations: 7 countries
• Sites: 9

Brief Summary

The purpose of this study is to find out whether rivaroxaban is safe and effective to use in children age newborn to less than 6 months and how long it stays in the body and how it is used in the body. Safety will be assessed by looking at the incidence and types of bleeding events. There will also be a check for worsening of blood clots.

Conditions

Thromboembolism

Keywords

Pediatric

Outcome Measures

Primary Outcomes (10)

• Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Day 1

  Concentration of pharmacokinetic parameters of rivaroxaban in plasma was evaluated.

  30 minutes to 1.5 hours post-dose; 2 to 4 hours post-dose (bid dosing) and 30 minutes to 3 hours post-dose; 7 to 8 hours post-dose on Day 1 (tid dosing)

• Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Day 3

  Concentration of pharmacokinetic parameters of rivaroxaban in plasma was evaluated.

  2 to 8 hours post-dose (bid dosing) and 30 minutes to 3 hours post-dose; 7 to 8 hours post-dose on Day 3 (tid dosing)

• Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Day 8

  Concentration of pharmacokinetic parameters of rivaroxaban in plasma was evaluated.

  10 to 16 hours post-dose on Day 8 (bid dosing)

• Change From Baseline in Prothrombin Time at Day 1

  Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.

  10-16 hours post-dose on Day 8 (baseline), 2-4 hours after the first dose on Day 1 (bid dosing) and 7-8 hours after the first dose on Day 1 (tid dosing)

• Change From Baseline in Prothrombin Time at Day 3

  Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.

  10-16 hours post-dose on Day 8 (baseline), 2-8 hours post-dose on Day 3 (bid dosing) and 0.5-3 hours post-dose on Day 3 (tid dosing)

• Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at Day 1

  The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway and is sensitive for deficiencies of factors I, II, V, VIII, IX, X, XI and XII.

  10-16 hours post-dose on Day 8 (baseline), 2-4 hours after the first dose on Day 1 (bid dosing) and 7-8 hours after the first dose on Day 1 (tid dosing)

• Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at Day 3

  The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway and is sensitive for deficiencies of factors I, II, V, VIII, IX, X, XI and XII.

  10-16 hours post-dose on Day 8 (baseline), 2-8 hours post-dose on Day 3 (bid dosing) and 0.5-3 hours post-dose on Day 3 (tid dosing)

• Anti-factor Xa Activity (Anti-Xa) Values at Day 1

  The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.

  2-4 hours after the first dose on Day 1 (bid dosing) and 7-8 hours after the first dose on Day 1 (tid dosing)

• Anti-factor Xa Activity (Anti-Xa) Values at Day 3

  The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.

  2-8 hours post-dose on Day 3 (bid dosing) and 0.5-3 hours post-dose on Day 3 (tid dosing)

• Anti-factor Xa Activity (Anti-Xa) Values at Day 8

  The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.

  10-16 hours post-dose on Day 8 (both bid and tid dosing)

Secondary Outcomes (2)

• Number of Participants With Major and Clinically Relevant Non-Major Bleeding Events

  From start of study drug administration until 30-day post study treatment period

• Number of Participants With Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging

  From start of study drug administration until 30-day post study treatment period

Study Arms (1)

Arm 1

EXPERIMENTAL

Rivaroxaban oral suspension from granules will be dosed according to body weight as oral 0.1% suspension (1 mg/mL)

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Interventions

Rivaroxaban (Xarelto, BAY59-7939) DRUG

Body weight adjusted dosing of rivaroxaban to achieve a similar exposure in the range as that observed in adults treated for venous thromboembolism (VTE) with 20 mg once daily.

Arm 1

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children from birth to less than 6 months with documented symptomatic or asymptomatic venous or arterial thrombosis who have been treated with anticoagulant therapy for at least 5 days.
• Gestational age at birth of at least 37 weeks.
• Hemoglobin, platelets, creatinine, ALT and total and direct bilirubin assessed within 10 days prior to enrollment.
• Oral feeding/nasogastric/gastric feeding for at least 10 days.
• Informed consent provided.
• Body weight \>2600 g

You may not qualify if:

• Active bleeding or high risk for bleeding contraindicating anticoagulant therapy, including history of intra-ventricular bleeding.
• Symptomatic progression of thrombosis during preceding anticoagulant treatment.
• Planned invasive procedures, including lumbar puncture and removal of non-peripherally placed central lines during study treatment.
• Hepatic disease which is associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase (ALT) \> 5x upper level of normal (ULN) or total bilirubin (TB) \> 2x ULN with direct bilirubin \> 20% of the total.
• Creatinine \>1.5 times of normal.
• Uncontrolled Hypertension defined as \>95th percentile.
• History of gastrointestinal disease or surgery associated with impaired absorption.
• Platelet count \<100 x 109/L.
• Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), e.g. all human immunodeficiency virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically (fluconazole is allowed)
• Concomitant use of strong inducers of CYP3A4, e.g. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
• Indication for anticoagulant therapy other than current thrombosis.
• Indication for antiplatelet therapy or non-steroid anti-inflammatory drug (NSAID) therapy. Incidental use is allowed.
• Hypersensitivity to rivaroxaban or its excipients.
• Participation in a study with an investigational drug or medical device within 30 days prior to enrollment.

Sponsors & Collaborators

• Bayer: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (9)

Unknown Facility

Vienna, 1090, Austria

Location

Unknown Facility

Montpellier, 34059, France

Location

Unknown Facility

Erlangen, 91052, Germany

Location

Unknown Facility

Ramat Gan, 5262000, Israel

Location

Unknown Facility

Milan, Lombardy, 20122, Italy

Location

Unknown Facility

Barcelona, 08035, Spain

Location

Unknown Facility

Madrid, 28007, Spain

Location

Unknown Facility

Madrid, 28046, Spain

Location

Unknown Facility

Izmir, 35-100, Turkey (Türkiye)

Location

Related Publications (1)

• Monagle P, Lensing AWA, Thelen K, Martinelli I, Male C, Santamaria A, Samochatova E, Kumar R, Holzhauer S, Saracco P, Simioni P, Robertson J, Grangl G, Halton J, Connor P, Young G, Molinari AC, Nowak-Gottl U, Kenet G, Kapsa S, Willmann S, Pap AF, Becka M, Twomey T, Beyer-Westendorf J, Prins MH, Kubitza D; EINSTEIN-Jr Phase 2 Investigators. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol. 2019 Oct;6(10):e500-e509. doi: 10.1016/S2352-3026(19)30161-9. Epub 2019 Aug 13.

  PMID: 31420317 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Thromboembolism

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

+1-888-84-22937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: October 1, 2015
• Study Start: November 19, 2015
• Primary Completion: December 18, 2017
• Study Completion: December 18, 2017
• Last Updated: July 10, 2018
• Results First Posted: July 10, 2018

Record last verified: 2018-06

Locations

AU (1); FR (1); IT (1); ES (3); IL (1); TU (1); DE (1)