Study Evaluating PK/PD and Safety of Betrixaban in Pediatric Patients

Study Overview
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Brief Summary
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A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Betrixaban in Pediatric Patients

Official Title
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A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Betrixaban in Pediatric Patients

Conditions
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VTE Prophylaxis

Intervention / Treatment
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* Drug: Betrixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients in the following age categories: 12 to < 18 years of age, 2 to < 12 years of age, and 28 days to < 2 years of age. Part 1 of the study will enroll only adolescent patients 12 to < 18 years of age. Patient is a pediatric subject requiring anticoagulant therapy, for example: Has previous thrombosis and completed a course of anti-coagulant therapy, and is considered to have a risk for recurrence of VTE, or Has any stable disease with a risk for arterial or venous thrombotic disorder, or Has any functional CVAD (Central Venous Access Device) in the upper or lower venous system. Patient has normalized coagulation parameters from recent anticoagulant therapy (INR or PTT, as appropriate) within 7 days of study drug administration. Exclusion Criteria: Patients who meet any one of the following exclusion criteria will be excluded from the study: Patient received any dose of anti-coagulant therapy within 7 days of Day 1. Patient has active bleeding or has a comorbid disorder that places the patient at high risk for bleeding. Patient has a comorbid disorder that places the patient at risk of death within 90 days of enrollment. Patient has abnormal coagulation tests at baseline. Patient has had recent or planned invasive procedures, including lumbar puncture and removal of non-peripherally placed central lines during study. Patient has hepatic disease associated with one or more of the following: Transaminase levels ≥ 2.5 × upper limit of normal (ULN) or bilirubin ≥ 1.5 × ULN at baseline. Coagulopathy leading to a clinically relevant bleeding risk, or hepatic transaminase level of > 2 × upper level of normal (ULN) or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total. Platelet count < 75 × 109/L or hemoglobin < 10.0 mg/dL. Hypertension defined as > 95th percentile for age. Refer to Appendix A. Patient has known congenital or acquired bleeding diathesis. Patient requires concomitant therapy with a strong P-gp inhibitor. Patient has previous history of any non-traumatic bleeding event that was life threatening or required medical attention. Patient had been administered thrombolytic therapy, or had undergone thrombectomy, or insertion of a caval filter to treat prior VTE. Patient has known inherited or acquired bleeding diathesis or coagulopathy. Patient has abnormal QTcF interval on baseline ECG. Patient will receive a dose of any antiplatelet medication (including aspirin) within 14 days before study drug dosing. Patient has malabsorption disorders (e.g., cystic fibrosis or short bowel syndrome). Patient has an estimated glomerular filtration rate (eGFR) < 30 mL/min. Patient is unable or reluctant to cooperate with the study procedures. Patient has hypersensitivity to other Factor Xa inhibitors, or the components of the dosage form. Patient has participated in a study with an investigational drug or medical device within 30 days prior to administration of betrixaban. Patient is female and is either pregnant or breastfeeding a child. Patient is sexually active and is not using medically accepted contraceptive method (if applicable).

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 17 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Bertrixaban/Andexanet<br>Single oral dose 40 mg | Drug: Betrixaban<br>* Factor Xa<br>|
| Experimental: Cohort 2 Bertrixaban/Placebo<br>Single oral dose 80 mg | Drug: Betrixaban<br>* Factor Xa<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) - AUC(0-∞) | Total area under the plasma concentration-time curve from 0 to infinity (AUC(0-∞)) | Day 1 - Day 6 (120 hours) | 
| Pharmacokinetic (PK) - Cmax | Maximum observed plasma concentration (Cmax) | Day 1 - Day 6 (120 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK - (AUC(0-last)) | Area under the concentration-time curve to the last measurable concentration above the quantitation limit (AUC(0-last)) | Day 1 - Day 6 | 
| PK - (t½) | Terminal plasma half-life (t½) | Day 1 - Day 6 | 
| PK - (Tmax) | Time to maximum observed plasma concentration (Tmax ) | Day 1 - Day 6 | 
| PK - (CL) | Clearance (CL) and volume of distribution (Vd) | Day 1 - Day 6 |