single ventricle physiology univentricular circulation
Conditions
Interventions
Part A: Subjects are treated with Open-label Rivaroxaban BID, equivalent dose
to 10mg once daily in adults.
Part B: 2/3 of the subjects are treated with Open-label Rivaroxaban BID,
equivalent dose t
Sponsors
Janssen-Cilag
Eligibility
Age
2 Years to 11 Years
Inclusion criteria
Inclusion criteria: 1. Boys or girls 2 to 8 years of age with single ventricle physiology and who have completed the initial Fontan procedure within 4 months prior to enrollment 2. Considered to be clinically stable by the investigator and able to tolerate oral or enteral administration of a suspension formulation and oral/enteral feedings 3. Satisfactory initial post-Fontan transthoracic echocardiographic screening as defined in the Post-Fontan Echocardiographic Examination Research Protocol 4. Parent/legally acceptable representative must sign an informed consent form (ICF) and child assent will also be provided, if applicable, according to local requirements
Exclusion criteria
Exclusion criteria: 1. Evidence of thrombosis, including those that are asymptomatic confirmed by post-Fontan procedure transthoracic echocardiogram, or other imaging techniques, during the screening period of the study 2. History of gastrointestinal disease or surgery associated with clinically relevant impaired absorption 3. History of or signs/symptoms suggestive of protein-losing enteropathy 4. Active bleeding or high risk for bleeding contraindicating antiplatelet or anticoagulant therapy, including a history of intracranial bleeding 5. Indication for anticoagulant or antiplatelet therapy other than current study. 6. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) 7. Platelet count 3x upper limit of normal (ULN) with concurrent total bilirubin >1.5x ULN with direct bilirubin >20% of the total at screening) 10. Known contraindication to ASA (subjects participating in Part B only) 11. Known allergies, hypersensitivity, or intolerance to rivaroxaban or its excipients 12. Inability to cooperate with study procedures 13. Combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (such as but not limited to ketoconazole, telithromycin, or protease inhibitors) use within 4 days before enrollment, or planned use during the study. Itraconazole use within 7 days before enrollment or planned use during the study. 14. Combined P-gp and strong CYP3A4 inducers (such as but not limited to rifampin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's Wort) use within 2 weeks before enrollment, or planned use during the study. 15. Planned use of drugs that are moderate CYP3A4 inhibitors (such as erythromycin) during the Initial PK, PD, and Safety Assessment Period of Part A only 16. Participation in a clinical study with an investigational drug or medical device in the previous 30 days prior to enrollment 17. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments 18. Family member of an employee of the investigator or study site with direct involvement in the proposed study or other studies under the direction of that investigator or study site.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A To characterize the single- and multiple-dose pharmacokinetics (PK) and PK/pharmacodynamics (PD) profiles after oral rivaroxaban therapy administered to pediatric subjects 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment. Part B To evaluate the safety and efficacy of rivaroxaban, administered twice daily (exposure matched to rivaroxaban 10 mg once daily in adults) compared to acetylsalicylic acid (ASA), given once daily (approximately 5 mg/kg) for thromboprophylaxis in pediatric subjects 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A To assess the safety and tolerability of rivaroxaban treatment. Part B To further characterize the PK and PK/PD profiles of rivaroxaban. | — |
Countries
Netherlands
Outcome results
None listed