A Phase 1, Open-Label, Single-Dose, Non-Randomized Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Betrixaban in Pediatric Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 20
- 主要终点
- Area Under The Plasma Concentration-Time Curve From 0 To Infinity (AUC(0-inf)) Of Betrixaban
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Pediatric participant who was assessed to be at risk for VTE but did not require immediate anticoagulant therapy, for example:
- •Had previous thrombosis and completed a course of anti-coagulant therapy, and is considered to have a risk for recurrence of VTE, or
- •Had any stable disease with a risk for arterial or venous thromboembolism, or
- •Had any functional central venous access device in the upper or lower venous system.
- •Participant had normalized coagulation parameters (international normalized ratio or partial thromboplastin time, as appropriate) within 7 days of study drug administration.
排除标准
- •Participants who meet any one of the following exclusion criteria were excluded from the study:
- •Participant received any dose of anti-coagulant therapy within 7 days of Day
- •Participant had active bleeding or had a comorbid disorder that placed the participant at high risk for bleeding.
- •Participant had a comorbid disorder that placed the participant at risk of death within 90 days of enrollment.
- •Participant had abnormal coagulation tests at baseline.
- •Participant had recent or planned invasive procedures, including lumbar puncture and removal of non-peripherally placed central lines during study.
- •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.
- •Participant had known congenital or acquired bleeding diathesis.
- •Participant required concomitant therapy with a strong P-glycoprotein inhibitor.
- •Participant had previous history of any non-traumatic bleeding event that was life threatening or required medical attention.
- •Participant had been administered thrombolytic therapy, or had undergone thrombectomy, or insertion of a caval filter to treat prior VTE.
- •Participant had known inherited or acquired bleeding diathesis or coagulopathy.
- •Participant had abnormal QTcF interval on baseline electrocardiogram.
- •Participant received a dose of any antiplatelet medication (including aspirin) within 14 days before study drug dosing.
- •Participant had malabsorption disorders (for example, cystic fibrosis or short bowel syndrome).
- •Participant had an estimated glomerular filtration rate < 30 milliliters/minute.
- •Participant was unable or reluctant to cooperate with the study procedures.
- •Participant had hypersensitivity to other Factor Xa inhibitors, or the components of the dosage form.
- •Participant had participated in a study with an investigational drug or medical device within 30 days prior to administration of betrixaban.
- •Participant was female and of childbearing potential and was either pregnant or breastfeeding a child.
- •Participant was sexually active and was not using medically accepted contraceptive method (if applicable).
研究组 & 干预措施
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.
干预措施: Betrixaban (Drug)
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.
干预措施: Betrixaban (Drug)
结局指标
主要结局
Area Under The Plasma Concentration-Time Curve From 0 To Infinity (AUC(0-inf)) Of Betrixaban
时间窗: Up to 6 days post dose
Following the Sponsor's decision to cease developing betrixaban, data for AUC(0-inf) were not collected.
Maximum Observed Plasma Concentration (Cmax) Of Betrixaban
时间窗: Up to 6 days post dose
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.
次要结局
- AUC To The Last Measurable Concentration Above The Quantitation Limit (AUC(0-last)) Of Betrixaban(Up to 6 days post dose)
- Apparent Total Body Clearance Of Betrixaban From Plasma (CL)(Up to 6 days post dose)
- Count Of Participants With Treatment-related Adverse Events(Up to 7 days post dose)
- Percent Change From Baseline In Thrombin Level At Day 6(Baseline, Day 6)
- Terminal Plasma Half-life (t½) Of Betrixaban(Up to 6 days post dose)
- Time To Maximum Observed Plasma Concentration (Tmax) Of Betrixaban(Up to 6 days post dose)
- Apparent Volume Of Distribution (Vd) Of Betrixaban(Up to 6 days post dose)