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

Study Overview
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Brief Summary
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To characterize the pharmacokinetic profile of rivaroxaban administered as granules for suspension formulation and to document safety and tolerability

Official Title
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Single-dose Study Testing Rivaroxaban Granules for Oral Suspension Formulation in Children From 2 Months to 12 Years With Previous Thrombosis

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br>Single arm, open label study | Drug: Rivaroxaban (Xarelto, BAY59-7939<br>* Single dose of reconstituted rivaroxaban granules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the curve) | Only PK will be tested in central lab | 4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration | 
| Cmax (maximum observed drug concentration) | Only PK will be tested in central lab | 4x within 8 hrs post study drug administrationh and 1x between 24-28h after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |