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

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