Thrombosis
Conditions
Brief summary
To characterize the pharmacokinetic profile of rivaroxaban administered as granules for suspension formulation and to document safety and tolerability
Interventions
DRUGRivaroxaban (Xarelto, BAY59-7939
Single dose of reconstituted rivaroxaban granules
Sponsors
Janssen Research & Development, LLC
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC (area under the curve) | 4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration | Only PK will be tested in central lab |
| Cmax (maximum observed drug concentration) | 4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration | Only PK will be tested in central lab |
Secondary
| 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 |
Countries
Belgium, Canada, Finland, France, Hungary, Italy, Spain, United States
Outcome results
None listed