Phase I Study on Rivaroxaban Granules for Oral Suspension Formulation in Children

Single-dose Study Testing Rivaroxaban Granules for Oral Suspension Formulation in Children From 2 Months to 12 Years With Previous Thrombosis

To characterize the pharmacokinetic profile of rivaroxaban administered as granules for suspension formulation and to document safety and tolerability

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• Finland
  • HUS, Finland, 00029
    • HUS Lastenklinikka
  • Turku, Finland, 20520
    • Turun yliopistollinen keskussairaala, kantasairaala
• France
  • Montpellier, France, 34059
    • Hôpital Arnaud de Villeneuve - Montpellier
  • Paris, France, 75015
    • Hopital Necker les enfants malades - Paris
• Hungary
  • Budapest, Hungary, 1094
    • University of Semmelweis/ Semmelweis Egyetem
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • A.O.U. Città della Salute e Della Scienza di Torino
  • Veneto
    • Padova, Veneto, Italy, 35128
      • A.O. di Padova
• Spain
  • Barcelona, Spain, 08035
    • Ciutat Sanitaria i Universitaria de la Vall d'Hebron
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Barcelona
    • Esplugues de LLobregat, Barcelona, Spain, 08950
      • Hospital de Sant Joan de Déu
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital Oakland
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Healthcare System
  • Ohio
    • Columbus, Ohio, United States, 43205-2696
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children with an age ≥2 months and weight between 3 and <12 kg, who have completed anticoagulant treatment at least 10 days prior to the planned study drug administration.

  • Gestational age at birth of at least 37 weeks
  • Oral feeding/ nasogastric/ gastric feeding for at least 10 days
• Normal PT and aPTT within 10 days prior to planned study drug administration
• Written informed consent provided and, if applicable, child assent provided

Exclusion Criteria:

• Active bleeding or high risk for bleeding, contraindicating anticoagulant therapy
• Planned invasive procedures, including removal of central lines, within 24 hours before and after single dose intake
• An estimate glomerular filtration rate (eGFR) < 30 mL/min/1.73m2

• Hepatic disease which is associated either with:

  • coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase (ALT) > 5x upper level of normal (ULN), or
  • total bilirubin > 2x ULN with direct bilirubin > 20% of the total.
• Platelet count < 50 x 10^9/L
• Hypertension (defined as systolic and/or diastolic blood pressure >95th percentile for age)
• Concomitant use of strong inhibitors of both CYP3A4 and P-glycoprotein, e.g., all human immunodeficiency virus protease inhibitors and the following azoleantimycotic agents: ketoconazole, itraconazole, voriconazole, and posaconazole, if used systemically (fluconazole is allowed)
• Concomitant use of strong inducers of CYP3A4, e.g., rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
• Inability to cooperate with the study procedures
• Hypersensitivity to rivaroxaban
• Participation in a study with an investigational drug other than rivaroxaban or a medical device within 30 days prior to treatment
• History of gastrointestinal disease or surgery associated with impaired absorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Single arm, open label study	Drug: Rivaroxaban (Xarelto, BAY59-7939; Single dose of reconstituted rivaroxaban granules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (area under the curve)	Only PK will be tested in central lab	4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration
Cmax (maximum observed drug concentration)	Only PK will be tested in central lab	4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Prothrombin time (PT)	Pre-administration, if not done within the past 10 days, and then 24-28 hours after drug administration
Activated partial thromboplastin time (aPTT)	Pre-administration, if not done within the past 10 days, and then 24-28 hours after drug administration
Composite of major bleeding and clinically relevant non-major bleeding	From dose administration until follow up call on day 8+3

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Research & Development, LLC

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer Healthcare products.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2015
• Primary Completion (Actual): May 22, 2018
• Study Completion (Actual): May 22, 2018

Study Registration Dates

• First Submitted: July 12, 2015
• First Submitted That Met QC Criteria: July 12, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 14, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 17992; 2015-000962-76 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No