Study Evaluating Betrixaban in Pediatric Participants

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

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).

Study Overview

• Status: Terminated
• Conditions: VTE Prophylaxis
• Intervention / Treatment: Drug: Betrixaban

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Kazan, Russian Federation, 420138
    • Children's Hospital of Tatarstan Republic
  • Kemerovo, Russian Federation, 650002
    • Federal State Institution
  • Moscow, Russian Federation, 125412
    • Pirogov Russian National Research Medical University
  • Moscow, Russian Federation, 119049
    • Children's City Clinical Hospital
  • Nizhny Novgorod, Russian Federation, 603136
    • State Budgetary Institution
  • Saint Petersburg, Russian Federation, 194100
    • Saint Petersburg State Pediatric Medical University
• Ukraine
  • Ivano-Frankivs'k, Ukraine, 76000
    • Ivano-Frankivsk Regional Children Clinical Hospital
  • Odesa, Ukraine
    • Odessa Regional Children Clinical Hospital
  • Sumy, Ukraine
    • Sumy Regional Children's Hospital
  • Vinnitsa, Ukraine
    • Vinnytsia Regional Children's Clinical Hospital, Department of Anesthesiology and Intensive Care
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Women's and Children's NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • Children's Hospital for Wales
  • Leicester, United Kingdom, LE3 9QP
    • Glenfield Hospital
  • London, United Kingdom, SE1 7EH
    • Evelina London Children's Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90036
      • ACTCA, Axis Clinical Trials
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Louisiana
    • New Orleans, Louisiana, United States, 70001
      • Tulane Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies & Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Betrixaban; Factor Xa inhibitor.; Other Names: PRT054021
Experimental: 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.	Drug: Betrixaban; Factor Xa inhibitor.; Other Names: PRT054021

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under The Plasma Concentration-Time Curve From 0 To Infinity (AUC(0-inf)) Of Betrixaban	Following the Sponsor's decision to cease developing betrixaban, data for AUC(0-inf) were not collected.	Up to 6 days post dose
Maximum Observed Plasma Concentration (Cmax) Of Betrixaban	Data reported as "0.200" indicates that the data are below the lower limit of quantification. Note that the Measure of Central Tendency could not be determined for Cohort 1 or Cohort 2 due to the values that are below the lower limit of quantification.	Up to 6 days post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC To The Last Measurable Concentration Above The Quantitation Limit (AUC(0-last)) Of Betrixaban	Following the Sponsor's decision to cease developing betrixaban, data for AUC(0-last) were not collected.	Up to 6 days post dose
Terminal Plasma Half-life (t½) Of Betrixaban	Following the Sponsor's decision to cease developing betrixaban, data for t½ were not collected.	Up to 6 days post dose
Time To Maximum Observed Plasma Concentration (Tmax) Of Betrixaban	The Tmax that the highest (maximum) Cmax of betrixaban was observed per group up to Day 6 (120 hours) post dosing is reported.	Up to 6 days post dose
Apparent Total Body Clearance Of Betrixaban From Plasma (CL)	Following the Sponsor's decision to cease developing betrixaban, data for CL were not collected.	Up to 6 days post dose
Apparent Volume Of Distribution (Vd) Of Betrixaban	Following the Sponsor's decision to cease developing betrixaban, data for Vd were not collected.	Up to 6 days post dose
Percent Change From Baseline In Thrombin Level At Day 6	Following the Sponsor's decision to cease developing betrixaban, data for thrombin levels were not collected.	Baseline, Day 6
Count Of Participants With Treatment-related Adverse Events	A treatment-related adverse event was any undesirable event or any untoward medical occurrence that occurs to a participant during the course of a study, or the protocol-defined time after study termination. An Investigator qualified in medicine made the determination of relationship to the investigational product for each adverse event (Unrelated, Unlikely Related, Possibly Related, or Probably Related). If the relationship between the adverse event and the investigational product was determined to be "possible" or "probable", the event was considered to be related to the investigational product for the purposes of expedited regulatory reporting. One participant experienced a mild study-drug-related headache that resolved in less than 2 hours. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Up to 7 days post dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic (PD) - Thrombin Level	The pharmacodynamic (PD) endpoint is the inhibition of thrombin generation during the first 24 hours post dosing, evaluated by the percent change in thrombin level from baseline.	Day 1 - Day 6
Number of patients with treatment related Adverse Events (AE)	The safety endpoint is the clinical assessment of AEs and other safety measurements (vital signs, ECGs, laboratory tests, etc.)	Day 1 - Day 6

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: Portola Pharmaceuticals, LLC (a wholly owned subsidiary of Alexion Pharmaceuticals)

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Actual): October 8, 2019
• Study Completion (Actual): October 8, 2019

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Betrixaban
• Other Study ID Numbers: 16-021; 2018-002562-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No