Clinical trial NCT03346083: Study Evaluating Betrixaban in Pediatric Participants
Official title: A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Betrixaban in Pediatric Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: VTE Prophylaxis
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Portola Pharmaceuticals, LLC (a wholly owned subsidiary of Alexion Pharmaceuticals)
First posted: 2017-11-17
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

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).

Primary outcomes:
measure: Area Under The Plasma Concentration-Time Curve From 0 To Infinity (AUC(0-inf)) Of Betrixaban
timeFrame: Up to 6 days post dose
measure: Maximum Observed Plasma Concentration (Cmax) Of Betrixaban
timeFrame: Up to 6 days post dose
Secondary outcomes:
measure: AUC To The Last Measurable Concentration Above The Quantitation Limit (AUC(0-last)) Of Betrixaban
timeFrame: Up to 6 days post dose
measure: Terminal Plasma Half-life (t½) Of Betrixaban
timeFrame: Up to 6 days post dose
measure: Time To Maximum Observed Plasma Concentration (Tmax) Of Betrixaban
timeFrame: Up to 6 days post dose
measure: Apparent Total Body Clearance Of Betrixaban From Plasma (CL)
timeFrame: Up to 6 days post dose
measure: Apparent Volume Of Distribution (Vd) Of Betrixaban
timeFrame: Up to 6 days post dose
measure: Percent Change From Baseline In Thrombin Level At Day 6
timeFrame: Baseline, Day 6
measure: Count Of Participants With Treatment-related Adverse Events
timeFrame: Up to 7 days post dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: ACTCA, Axis Clinical Trials
state: California
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital
state: Ohio
city: Kazan
country: Russian Federation
facility: Children's Hospital of Tatarstan Republic
city: Kemerovo
country: Russian Federation
facility: Federal State Institution
city: Moscow
country: Russian Federation
facility: Children's City Clinical Hospital
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
city: Nizhny Novgorod
country: Russian Federation
facility: State Budgetary Institution
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical University
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano-Frankivsk Regional Children Clinical Hospital
city: Odesa
country: Ukraine
facility: Odessa Regional Children Clinical Hospital
city: Sumy
country: Ukraine
facility: Sumy Regional Children's Hospital
city: Vinnitsa
country: Ukraine
facility: Vinnytsia Regional Children's Clinical Hospital, Department of Anesthesiology and Intensive Care
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Children's Hospital for Wales
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
Study officials:
References: