Clinical trial NCT02497716: Phase I Study on Rivaroxaban Granules for Oral Suspension Formulation in Children
Official title: Single-dose Study Testing Rivaroxaban Granules for Oral Suspension Formulation in Children From 2 Months to 12 Years With Previous Thrombosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thrombosis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2015-07-14
Enrollment: 47
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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


Eligibility criteria: 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

Primary outcomes:
measure: AUC (area under the curve)
timeFrame: 4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration
measure: Cmax (maximum observed drug concentration)
timeFrame: 4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration
Secondary outcomes:
measure: Prothrombin time (PT)
timeFrame: Pre-administration, if not done within the past 10 days, and then 24-28 hours after drug administration
measure: Activated partial thromboplastin time (aPTT)
timeFrame: Pre-administration, if not done within the past 10 days, and then 24-28 hours after drug administration
measure: Composite of major bleeding and clinically relevant non-major bleeding
timeFrame: From dose administration until follow up call on day 8+3
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: HUS
country: Finland
facility: HUS Lastenklinikka
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala, kantasairaala
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve - Montpellier
city: Paris
country: France
facility: Hopital Necker les enfants malades - Paris
city: Budapest
country: Hungary
facility: University of Semmelweis/ Semmelweis Egyetem
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino
state: Piemonte
city: Padova
country: Italy
facility: A.O. di Padova
state: Veneto
city: Esplugues de LLobregat
country: Spain
facility: Hospital de Sant Joan de Déu
state: Barcelona
city: Barcelona
country: Spain
facility: Ciutat Sanitària i Universitaria de la Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: