Study Evaluating Betrixaban in Pediatric Participants

NCT ID: NCT03346083

Last Updated: 2024-01-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-13
• Study Completion Date: 2019-10-08

Brief Summary

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).

Detailed 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.

Conditions

VTE Prophylaxis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Betrixaban 40 mg

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

Group Type: EXPERIMENTAL

Betrixaban

Intervention Type: DRUG

Factor Xa inhibitor.

Cohort 2: Betrixaban 80 mg

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

Group Type: EXPERIMENTAL

Betrixaban

Intervention Type: DRUG

Factor Xa inhibitor.

Interventions

Betrixaban

Factor Xa inhibitor.

Intervention Type: DRUG

Other Intervention Names

PRT054021

Eligibility Criteria

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

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).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Portola Pharmaceuticals, LLC (a wholly owned subsidiary of Alexion Pharmaceuticals)

INDUSTRY

Sponsor Role: collaborator

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

ACTCA, Axis Clinical Trials

Los Angeles, California, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Tulane Medical Center

New Orleans, Louisiana, United States

Rainbow Babies & Children's Hospital

Cleveland, Ohio, United States

Children's Hospital of Tatarstan Republic

Kazan', , Russia

Federal State Institution

Kemerovo, , Russia

Children's City Clinical Hospital

Moscow, , Russia

Pirogov Russian National Research Medical University

Moscow, , Russia

State Budgetary Institution

Nizhny Novgorod, , Russia

Saint Petersburg State Pediatric Medical University

Saint Petersburg, , Russia

Ivano-Frankivsk Regional Children Clinical Hospital

Ivano-Frankivsk, , Ukraine

Odessa Regional Children Clinical Hospital

Odesa, , Ukraine

Sumy Regional Children's Hospital

Sumy, , Ukraine

Vinnytsia Regional Children's Clinical Hospital, Department of Anesthesiology and Intensive Care

Vinnitsa, , Ukraine

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, , United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Children's Hospital for Wales

Cardiff, , United Kingdom

Glenfield Hospital

Leicester, , United Kingdom

Evelina London Children's Hospital

London, , United Kingdom

Countries

United States; Russia; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002562-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16-021

Identifier Type: -

Identifier Source: org_study_id