VTE Prophylaxis Clinical Trial
Official title:
A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Betrixaban in Pediatric Patients
| Verified date | April 2023 |
| Source | Alexion Pharmaceuticals, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Terminated |
| Enrollment | 21 |
| Est. completion date | October 8, 2019 |
| Est. primary completion date | October 8, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 17 Years |
| Eligibility | 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). |
| Country | Name | City | State |
|---|---|---|---|
| Russian Federation | Children's Hospital of Tatarstan Republic | Kazan | |
| Russian Federation | Federal State Institution | Kemerovo | |
| Russian Federation | Children's City Clinical Hospital | Moscow | |
| Russian Federation | Pirogov Russian National Research Medical University | Moscow | |
| Russian Federation | State Budgetary Institution | Nizhny Novgorod | |
| Russian Federation | Saint Petersburg State Pediatric Medical University | Saint Petersburg | |
| Ukraine | Ivano-Frankivsk Regional Children Clinical Hospital | Ivano-Frankivs'k | |
| 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 | |
| United Kingdom | 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 States | Children's Healthcare of Atlanta | Atlanta | Georgia |
| United States | Rainbow Babies & Children's Hospital | Cleveland | Ohio |
| United States | ACTCA, Axis Clinical Trials | Los Angeles | California |
| United States | Children's Hospital Los Angeles | Los Angeles | California |
| United States | Tulane Medical Center | New Orleans | Louisiana |
| Lead Sponsor | Collaborator |
|---|---|
| Alexion Pharmaceuticals, Inc. | Portola Pharmaceuticals, LLC (a wholly owned subsidiary of Alexion Pharmaceuticals) |
United States, Russian Federation, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 |