A Phase II, Parallel Group, Randomized, Multicentre, Open Label Study to Compare the Pharmacokinetics of Tacrolimus in De Novo Pediatric Allograft Recipients Treated With an Advagraf® or Prograf® Based Immunosuppressive Regimen, Including a Long-Term Follow-Up
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 10
- 主要终点
- Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus (Part A)
研究概览
简要总结
The purpose of this study is to compare how the body absorbs and processes two different formulations of the anti-rejection medication tacrolimus (Advagraf® or Prograf®) in children receiving an organ transplant, and how safe and effective they are over a longer period of time.
This study is for children less than 16 years old. No minimum age has been set, however, to be included in this study participants must able to swallow the medication capsules intact.
详细描述
Participants undergoing primary heart, kidney or liver transplantation and meeting the Inclusion Criteria and complying with the Exclusion Criteria prior to initiation of tacrolimus therapy will be enrolled.
Participants will be randomized to treatment with either Advagraf® or Prograf®. The randomization will be on a 1:1 basis stratified by organ and centre.
The study is divided in to two parts:
Part A: The initial pharmacokinetic part of the study.
Part B: A long term follow-up of one year. The main objective of Part A of the study is to collect PK data following administration of Advagraf® and Prograf® in de novo pediatric allograft recipients. Part B allows comparison of the safety and efficacy profiles of Advagraf® vs. Prograf® for longer term (52 weeks) post allograft transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- — 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject is aged <16 years of age, undergoing primary liver, kidney or heart allograft transplantation
- •The subject must be able to swallow intact Prograf® or Advagraf® capsules
- •Subjects, treated since transplantation with Basiliximab or ATG/ Mycophenolate Mofetil (MMF)/steroids, whose gastric motility has resumed and whose renal function is adequate on Day 1 (Heart only)
排除标准
- •Subject is receiving a multi-organ transplant or has previously received an organ transplant (including re-transplantation)
- •Subject with pulmonary vascular resistance ≥4 Wood units despite medication
- •Subject with significant renal impairment, defined as having serum creatinine ≥230 μmol/l (≥2.6 mg/dl) pre-transplantation. (Not applicable for renal transplanted subjects)
- •Subject with significant liver disease, defined as having continuously elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels of ≥3 times the upper value of the normal range of the investigational site during the past 28 days. (Not applicable for liver transplanted subjects)
- •Subject with malignancies or a history of malignancy within the last 5 years, with the exception of those with basalioma or squamous cell carcinoma of the skin that has been treated successfully. (Not applicable for transplanted subjects with a primary organ diagnosis of cancer)
- •Subject requiring systemic immunosuppressive medication for any other indication than transplantation
研究组 & 干预措施
Tacrolimus
Participants receive tacrolimus twice daily starting from day 1 for 4 weeks for in Part A, and continue to receive tacrolimus twice daily up to end of Part B and C of the study.
干预措施: Tacrolimus (Drug)
Tacrolimus Prolonged Release
Participants receive tacrolimus prolonged release once daily starting from day 1 for 4 weeks for in Part A, and continue to receive tacrolimus prolonged release once daily up to end of Part B and of the study.
干预措施: Tacrolimus prolonged release (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus (Part A)
时间窗: Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
Number of Participants with Adverse Events (Part A + B)
时间窗: From first dose of study drug up to 7 days after last dose of study drug in Part B (up to 53 weeks)
Safety is assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important.
Number of Participants with Adverse Events (Part C)
时间窗: Up to 9 years
Safety is assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important.
次要结局
- Trough Concentration (C24) for Tacrolimus (Part A)(Days 1, 7 and 28, 24 hours after dosing)
- Correlation between AUC24 & C24 (Part A)(Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose)
- Maximum Concentration (Cmax) of Tacrolimus (Part A)(Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose)
- Time to Attain Maximum Concentration (tmax) of Tacrolimus (Part A)(Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose)
- Trough Concentration (C12) for Tacrolimus (Part A)(Days 1, 7 and 28, 12 hours after dosing)
- Number of Participants with Acute Rejections (Part A + B)(Up to Week 52)
- Number of Participants with Biopsy-proven Acute Rejection Episodes (BPARs) (Part A + B)(Up to Week 52)
- Severity of Biopsy Proven Acute Rejection Episodes (Part A + B)(Up to Week 52)
- Patient Survival (Part A + B)(Up to Week 52)
- Graft Survival (Part A + B)(Up to Week 52)
- Efficacy Failure (Part A + B)(Up to Week 52)