临床试验/NCT02846532

NCT02846532已完成3 期

A Prospective, Open-Label, Active-Controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Rivaroxaban for Thromboprophylaxis in Pediatric Subjects 2 to 8 Years of Age After the Fontan Procedure

Janssen Research & Development, LLC0 个研究点目标入组 112 人开始时间: 2016年11月16日最近更新: 2025年3月30日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方: Janssen Research & Development, LLC
入组人数: 112
主要终点: Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

The Purpose of this study is to characterize the single and multiple-dose pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/ PD) profiles after oral rivaroxaban therapy administered to pediatric participants 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment (Part A) and to evaluate the safety and efficacy of rivaroxaban, administered twice daily (exposure matched to rivaroxaban 10 milligram [mg] once daily in adults) compared to acetylsalicylic acid (ASA), given once daily (approximately 5 milligram per kilogram [mg/kg]) for thromboprophylaxis in pediatric participants 2 to 8 years of age with single ventricle physiology who have completed the Fontan procedure within 4 months prior to enrollment.

详细描述

Part A: This part includes a 12-day Initial PK, PD, and Safety Assessment Period. Participants in Part A will not participate in Part B. Randomization in Part B of this study will begin once the cumulative data from the Initial PK, PD, and Safety Assessment Period in Part A are deemed acceptable by the Independent Data Monitoring Committee. Part A of the study will consist of an up to 21-day Screening Period, a 12-day Initial PK, PD, and Safety Assessment Period, a 12-month Open-Label Treatment Period, and a 30-day Follow-Up phone contact. Part B: Participants will be randomly assigned to two treatment groups and randomization ratio will be 2:1 for rivaroxaban and ASA. ASA will be used as control. There will be an up to a 21-day Screening Period, a 12 month Open-Label Treatment Period and a 30-day Follow-Up phone contact.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Prevention
盲法: None

入排标准

年龄范围: 2 Years 至 8 Years（Child）
性别: All
接受健康志愿者: 否

入选标准

•Participant must be considered to be clinically stable by the investigator and able to tolerate oral or enteral administration of a suspension formulation and oral/enteral feedings
•Satisfactory initial post-Fontan transthoracic echocardiographic Screening as defined in the Post-Fontan Echocardiographic Examination Research Protocol
•Parent/legally acceptable representative must sign an informed consent form (ICF) and child assent will also be provided, if applicable, according to local requirements

排除标准

•Evidence of thrombosis, including those that are asymptomatic confirmed by post-Fontan procedure transthoracic echocardiogram, or other imaging techniques, during the Screening period of the study
•History of gastrointestinal disease or surgery associated with clinically relevant impaired absorption
•History of or signs/symptoms suggestive of protein-losing enteropathy
•Active bleeding or high risk for bleeding contraindicating antiplatelet or anticoagulant therapy, including a history of intracranial bleeding
•Platelet count less than (<)50*10^9/Liters (L) at Screening
•Estimated glomerular filtration rate (eGFR) <30 milliliters per minute per 1.73 meter square (mL/min/1.73m^2)
•Known clinically significant liver disease

研究组 & 干预措施

Rivaroxaban

Experimental

干预措施: Rivaroxaban (Drug)

Acetylsalicylic Acid

Experimental

干预措施: Acetylsalicylic Acid (Drug)

结局指标

主要结局

Percentage of Participants With Any Thrombotic Event (Venous or Arterial and Symptomatic or Asymptomatic)

时间窗: Up to 12 months

Thrombotic event was defined as the appearance of a new thrombotic burden within the cardiovascular system on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus (such as cardioembolic stroke, pulmonary embolism). The event included ischemic stroke, pulmonary embolism, venous thrombosis, arterial/intracardiac thrombosis, and other thrombosis.

Plasma Concentration of Rivaroxaban at Day 1 (0.5-1.5 Hours Postdose)

时间窗: Day 1: 0.5-1.5 hours postdose

Plasma rivaroxaban concentrations for Parts A and B were assessed. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.

Plasma Concentration of Rivaroxaban at Day 1 (1.5-4 Hours Postdose)

时间窗: Day 1: 1.5-4 hours postdose

Absolute PT at Day 4 (6-8 Hours Postdose)

时间窗: Day 4: 6-8 hours postdose

Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.

Plasma Concentration of Rivaroxaban at Day 4 (Up to 3 Hours Predose)

时间窗: Day 4: Up to 3 hours predose

Plasma Concentration of Rivaroxaban at Day 4 (0.5-1.5 Hours Postdose)

时间窗: Day 4: 0.5-1.5 hours postdose

Plasma Concentration of Rivaroxaban at Day 4 (1.5-4 Hours Postdose)

时间窗: Day 4: 1.5-4 hours postdose

Plasma Concentration of Rivaroxaban at Day 4 (6-8 Hours Postdose)

时间窗: Day 4: 6-8 hours postdose

Plasma Concentration of Rivaroxaban at Month 3 (Up to 3 Hours Predose)

时间窗: Month 3: Up to 3 hours predose

Plasma Concentration of Rivaroxaban at Month 3 (0.5-1.5 Hours Postdose)

时间窗: Month 3: 0.5-1.5 hours postdose

Plasma Concentration of Rivaroxaban at Month 3 (2.5-4 Hours Postdose)

时间窗: Month 3: 2.5-4 hours postdose

Percentage of Participants With Bleeding Events

时间窗: Up to 12 months

Bleeding events were categorized into major, clinically relevant non-major bleeding (CRNM), and trivial bleeding events. Major bleeding: overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more; or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults; or occurring in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or contributing to death. CRNM bleeding: overt bleeding not meeting the criteria for major bleeding but associated with: Medical intervention, or Unscheduled contact with a physician, cessation of study treatment, or Discomfort for the subject such as pain, or Impairment of activities of daily life. Trivial bleeding: any other overt bleeding event that does not meet criteria for CRNM bleeding.

Absolute Prothrombin Time (PT) at Day 1 (0.5-1.5 Hours Postdose)

时间窗: Day 1: 0.5-1.5 hours postdose

Absolute prothrombin time was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.

Absolute PT at Day 1 (1.5-4 Hours Postdose)

时间窗: Day 1: 1.5-4 hours postdose

Absolute PT at Day 4 (Up to 3 Hours Predose)

时间窗: Day 4: Up to 3 hours predose

Absolute PT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here.

Absolute PT at Day 4 (0.5-1.5 Hours Postdose)

时间窗: Day 4: 0.5-1.5 hours postdose

Absolute PT at Day 4 (1.5-4 Hours Postdose)

时间窗: Day 4: 1.5-4 hours postdose

Absolute PT at Month 3 (Up to 3 Hours Predose)

时间窗: Month 3: Up to 3 hours predose

Absolute PT at Month 3 (0.5-1.5 Hours Postdose)

时间窗: Month 3: 0.5-1.5 hours postdose

Absolute PT at Month 3 (2.5-4 Hours Postdose)

时间窗: Month 3: 2.5-4 hours postdose

Activated Partial Thromboplastin Time (aPTT) at Day 1 (0.5-1.5 Hours Postdose)

时间窗: Day 1: 0.5-1.5 hours postdose

aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.

aPTT at Day 1 (1.5-4 Hours Postdose)

时间窗: Day 1: 1.5-4 hours postdose

aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and average of the participants included in the given time-range is presented here.

aPTT at Day 4 (Up to 3 Hours Predose)

时间窗: Day 4: Up to 3 hours predose

aPTT at Day 4 (0.5-1.5 Hours Postdose)

时间窗: Day 4: 0.5-1.5 hours postdose

aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average the participants included in the given time-range is presented here.

aPTT at Day 4 (1.5-4 Hours Postdose)

时间窗: Day 4: 1.5-4 hours postdose

aPTT was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average for the participants included in the given time-range is presented here.

aPTT at Day 4 (6-8 Hours Postdose)

时间窗: Day 4: 6-8 hours postdose

aPTT at Month 3 (Up to 3 Hours Predose)

时间窗: Month 3: Up to 3 hours predose

aPTT at Month 3 (0.5-1.5 Hours Postdose)

时间窗: Month 3: 0.5-1.5 hours postdose

aPTT at Month 3 (2.5-4 Hours Postdose)

时间窗: Month 3: 2.5-4 hours postdose

Anti-FXa at Day 1 (0.5-1.5 Hours Postdose)

时间窗: Day 1: 0.5-1.5 hours postdose

Anti-FXa was assessed as pharmacodynamic parameter. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here.

Anti-FXa at Day 1 (1.5-4 Hours Postdose)

时间窗: Day 1: 1.5-4 hours postdose

Anti-FXa at Day 4 (6-8 Hours Postdose)

时间窗: Day 4: 6-8 hours postdose

Anti-FXa at Month 3 (Up to 3 Hours Predose)

时间窗: Month 3: Up to 3 hours predose

Anti-FXa at Month 3 (0.5-1.5 Hours Postdose)

时间窗: Month 3: 0.5-1.5 hours postdose

Anti-FXa at Month 3 (2.5-4 Hours Postdose)

时间窗: Month 3: 2.5-4 hours postdose

次要结局

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to 12 months)

研究者

发起方

Janssen Research & Development, LLC

申办方类型

Industry

责任方

Sponsor

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