Study Evaluating Betrixaban in Pediatric Participants

Alexion Pharmaceuticals

Status and phase: Terminated; Phase 1

Conditions: VTE Prophylaxis

Treatments: Drug: Betrixaban

Study type: Interventional

Funder types: Industry

Identifiers

NCT03346083

2018-002562-40 (EudraCT Number)

16-021

Details and patient eligibility

About

This trial was a Phase 1, open-label, multicenter study of the pharmacokinetics (PK), pharmacodynamics (PD), and safety of a single dose of betrixaban in pediatric participants at risk of venous thromboembolism (VTE).

Full description

This study was to be conducted in 2 parts: Part 1 and Part 2. Part 1 (the initial opening of the study) was conducted in 21 adolescent participants (12 to < 18 years of age) who were assessed to be at risk for VTE. Participants in Part 1 received either 40 or 80 milligrams (mg) of study drug. The PK and PD data from Part 1 was to be used for dose determination for the next youngest age group using population PK and physiological-based PK modeling and simulation. Following analysis of Part 1 data, Part 2 of the study was to commence and enroll 12 participants 2 to < 12 years of age. However, after completion of Part 1 and prior to initiating Part 2, the Sponsor decided to cease developing betrixaban, prompting early study closure.

Enrollment: 21 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Pediatric participants in the following age categories: 12 to < 18 years of age and 2 to < 12 years of age. Part 1 of the study enrolled only adolescent participants 12 to < 18 years of age.

2. Pediatric participant who was assessed to be at risk for VTE but did not require immediate anticoagulant therapy, for example:

   1. Had previous thrombosis and completed a course of anti-coagulant therapy, and is considered to have a risk for recurrence of VTE, or
   2. Had any stable disease with a risk for arterial or venous thromboembolism, or
   3. Had any functional central venous access device in the upper or lower venous system.

3. Participant had normalized coagulation parameters (international normalized ratio or partial thromboplastin time, as appropriate) within 7 days of study drug administration.

Exclusion criteria

Participants who meet any one of the following exclusion criteria were excluded from the study:

1. Participant received any dose of anti-coagulant therapy within 7 days of Day 1.

2. Participant had active bleeding or had a comorbid disorder that placed the participant at high risk for bleeding.

3. Participant had a comorbid disorder that placed the participant at risk of death within 90 days of enrollment.

4. Participant had abnormal coagulation tests at baseline.

5. Participant had recent or planned invasive procedures, including lumbar puncture and removal of non-peripherally placed central lines during study.

6. Participant had 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 × ULN or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total.
   • Platelet count < 75 × 10^9/liter or hemoglobin < 10.0 mg/deciliter.
   • Hypertension.

7. Participant had known congenital or acquired bleeding diathesis.

8. Participant required concomitant therapy with a strong P-glycoprotein inhibitor.

9. Participant had previous history of any non-traumatic bleeding event that was life threatening or required medical attention.

10. Participant had been administered thrombolytic therapy, or had undergone thrombectomy, or insertion of a caval filter to treat prior VTE.

11. Participant had known inherited or acquired bleeding diathesis or coagulopathy.

12. Participant had abnormal QTcF interval on baseline electrocardiogram.

13. Participant received a dose of any antiplatelet medication (including aspirin) within 14 days before study drug dosing.

14. Participant had malabsorption disorders (for example, cystic fibrosis or short bowel syndrome).

15. Participant had an estimated glomerular filtration rate < 30 milliliters/minute.

16. Participant was unable or reluctant to cooperate with the study procedures.

17. Participant had hypersensitivity to other Factor Xa inhibitors, or the components of the dosage form.

18. Participant had participated in a study with an investigational drug or medical device within 30 days prior to administration of betrixaban.

19. Participant was female and of childbearing potential and was either pregnant or breastfeeding a child.

20. Participant was sexually active and was not using medically accepted contraceptive method (if applicable).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 2 patient groups

Cohort 1: Betrixaban 40 mg

Experimental group

Description:

Participants received a single, oral dose of betrixaban at 40 mg in a fed state, and had 10 PK blood sampling time points.

Treatment:

Drug: Betrixaban

Cohort 2: Betrixaban 80 mg

Experimental group

Description:

Participants received a single, oral dose of betrixaban at 80 mg in a fed state, and had 5 PK sampling time points.

Treatment:

Drug: Betrixaban