EINSTEIN Junior Phase II: Oral Rivaroxaban in Young Children With Venous Thrombosis

Major bleeding is defined as overt bleeding and: * associated with a fall in hemoglobin of 2 gram/decilitre (g/dL) or more, or * leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or * occurring in a critical site, for example (e.g.) intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or * contributing to death. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding, but associated with: * medical intervention, or * unscheduled contact (visit or telephone call) with a physician, or * cessation (temporary) of study treatment, or * discomfort for the child such as pain or * impairment of activities of daily life (such as loss of school days or hospitalization).

Time frame: During or within 2 days after stop of study treatment (up to 32 days)

Population: SAF included all subjects who received at least one dose of the study medication.

The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway. Day 30 (10-16 hours post-dose) was considered as a baseline.

Time frame: Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose); Day 30 (10-16 hours post-dose)

Population: PDS with evaluable subjects for this end point. PD parameters were evaluated only for subjects who received active study medication.

Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade. Day 30 (10-16 hours post-dose) was considered as a baseline.

Time frame: Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose); Day 30 (10-16 hours post-dose)

Population: PDS with evaluable subjects for this end point. PD parameters were evaluated only for subjects who received active study medication.

Concentration of rivaroxaban in plasma was measured at Day 1, 15 and 30 at specified time points. In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

Time frame: Day 1 (30-90 minutes, 2.5-4 hours post-dose); Day 15 (2-8 hours post-dose) and Day 30 (10-16 hours post-dose)

Population: PKS included all subjects with at least one pharmacokinetic sample in accordance with the pharmacokinetic sampling strategy.

The occurrence of asymptomatic deterioration in thrombotic burden was summarized by age group. At the end of the 30-day treatment period, a repeat imaging of the thrombus was performed. The images of the index event and repeat imaging were adjudicated by the central independent adjudication committee (CIAC). The thrombotic burden at the time of the index event was compared to the thrombotic burden at the time of repeat imaging. The outcome of the adjudication was classified as normalized, improved, no relevant change, deteriorated, or not evaluable. Due to missing repeated imaging, thrombotic burden assessments were not done in some subjects.

Time frame: At the end of the 30-day treatment period

Population: FAS included all enrolled children (before Amendment 4, all children were randomized by interactive voice/web response system \[IxRS\], after Amendment 4 all children were assigned to rivaroxaban by IxRS). Screening failures were excluded.

Venous thromboembolism is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. The occurrence of recurrent venous thromboembolism was summarized by age group. Symptomatic recurrence, which is the composite of deep Vein Thrombosis (DVT), non-fatal Pulmonary Embolism (PE), and fatal PE of venous thrombosis, had to be documented using appropriate (repeat) imaging test.

Time frame: From start of the study treatment up to 30-days post study treatment period (approximately 60 days)

Population: FAS included all enrolled children (before Amendment 4, all children were randomized by interactive voice/web response system \[IxRS\], after Amendment 4 all children were assigned to rivaroxaban by IxRS). Screening failures were excluded.

The individual anti-Factor Xa activity was determined ex-vivo using a photometric method. The anti-factor Xa assay is designed to measure plasma heparin, low molecular weight heparin and other anticoagulants. In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Time frame: Day 1 (2.5-4 hours post-dose); Day 15 (2-8 hours post-dose) and Day 30 (10-16 hours post-dose)

Population: PDS included all subjects with at least one blood sample for clotting tests in accordance with the pharmacodynamic sampling strategy was included.