A Multicenter, Open-label, Non-comparative Study of Modigraf® (Tacrolimus Granules) to Evaluate the Pharmacokinetics and Long-term Safety and Efficacy in De Novo Pediatric Allograft Liver and Kidney Transplantation Recipients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 4
- 主要终点
- Pharmacokinetics (PK) of tacrolimus granules in whole blood: area under the blood concentration - time curve for a dosing interval (AUCtau) on Day 1
研究概览
简要总结
The purpose of this study is to determine the pharmacokinetics of tacrolimus following oral administration of Modigraf, after the first oral dose and at steady state in pediatric participants undergoing de novo allograft liver or kidney transplantation. This study will also observe the safety and efficacy of Modigraf in de novo pediatric allograft liver and kidney transplantation recipients.
详细描述
Pediatric participants will be treated with a Modigraf (tacrolimus granules) based immunosuppressive regimen for 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant's parent(s) or their legal representative(s), and participant where applicable agrees not to participate in another interventional study while participating in the present study from 1 month before screening to the end of the study.
排除标准
- •Participant has previously received another organ transplant.
- •Participant has a high immunological risk, defined as a panel reactive antibody (PRA) score > 50% in the previous 6 months (only applicable for kidney transplantation recipients).
- •Cold ischemia time of the donor kidney longer than 30 hours (only applicable for kidney transplantation recipients).
- •Bilateral kidney transplantation recipients (only applicable for kidney transplantation recipients).
- •Participant receives an ABO incompatible donor organ.
- •Participant has significant kidney impairment, defined as having serum creatinine ≥ 230 μmol/L (≥ 2.6 mg/dL) prior to transplantation (not applicable for kidney transplantation recipients).
- •Participant has significant liver disease, defined as having elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or total bilirubin (TBL) levels 3 times the upper value of the normal range prior to transplantation (not applicable for liver transplantation recipients).
- •Participants with malignancies or a history of malignancy within the last 5 years.
- •Participant has a significant, uncontrolled systemic infection and/or severe diarrhea, vomiting, active upper gastrointestinal disorder that may affect the absorption of tacrolimus or has an active peptic ulcer.
- •Recipient or donor known to be human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) positive.
- •Participant requires systemic immunosuppressive medication for any indication other than transplantation.
- •Participants taking or requiring to be treated with medication or substances prohibited by this protocol.
- •Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab, or tacrolimus.
- •Participants with severe primary disease/complications/poor general condition which may be unsuitable for participating in this study.
- •Participant is currently participating in another clinical trial and/or has been taking any other study drug within 1 month prior to screening.
- •Participant is unlikely to comply with the visits scheduled in the protocol.
研究组 & 干预措施
Liver Transplant
Pediatric participants who undergo de novo allograft liver transplantation receive initial daily dose of 0.2 milligram per kilogram (mg/kg) of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
干预措施: Tacrolimus granules (Drug)
Kidney Transplant
Pediatric participants who undergo de novo allograft kidney transplantation receive initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
干预措施: Tacrolimus granules (Drug)
结局指标
主要结局
Pharmacokinetics (PK) of tacrolimus granules in whole blood: area under the blood concentration - time curve for a dosing interval (AUCtau) on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
AUCtau is recorded from the pharmacokinetic (PK) whole blood samples collected.
PK of tacrolimus granules in Whole Blood: Time of Maximum Concentration (Tmax) on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Tmax is recorded from the PK blood samples collected. Tmax is time of maximum concentration in an observation period.
Correlation between Ctrough and AUCtau of tacrolimus granules PK parameters in whole blood on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
The correlation between Ctrough and AUCtau PK parameters will be assessed by Pearson's coefficient at each sample time by visit.
PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Ctrough normalized with the dose just prior to blood sampling. Dose-normalized Ctrough is calculated as Ctrough/dose.
PK of tacrolimus granules in whole blood: AUCtau on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
AUCtau is recorded from the PK blood samples collected.
PK of tacrolimus granules in whole blood: Cmax on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Cmax is recorded from the PK blood samples collected. Cmax is maximum concentration observed in an observation period.
PK of tacrolimus granules in Whole Blood: Tmax on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Tmax is recorded from the PK blood samples collected. Tmax is time of maximum concentration in an observation period.
Number of Participants who Died
时间窗: From first dose to month 12
Number of participant who died is recorded during 12 months' post-transplant; any cause of death is taken into account.
Number of Participants with Graft Failure
时间窗: From first dose to month 12
Graft failure is defined as graft dysfunction, including re-transplantation or death, during the study period. A graft dysfunction to permanent dialysis in kidney transplantation is also considered as graft failure.
Number of Dose Adjustments Throughout the Study Period
时间窗: From first dose to month 12
The dose adjustments required for the organ transplant is reported.
Whole Blood Trough Levels of Tacrolimus
时间窗: From day 1 through month 12 (predose)
Tacrolimus whole blood trough levels are routinely monitored from whole blood samples, using a local assay method, for example EMITÒ or Liquid-Chromatography-Mass-Spectrometry-Mass-Spectrometry (LC-MS-MS) in the local laboratories. Mean trough levels of tacrolimus from day 1 through month 12 are reported.
PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Dose-normalized Cmax is Cmax normalized with the dose just prior to blood sampling. Dose-normalized Cmax is calculated as Cmax/dose.
PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Dose-normalized Cmax is Cmax normalized with the dose just prior to blood sampling. Dose-normalized Cmax is calculated as Cmax/dose.
PK of tacrolimus granules in whole blood: maximum concentration (Cmax) on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Cmax is recorded from the PK blood samples collected. Cmax is maximum concentration observed in an observation period.
Correlation between Ctrough and AUCtau of tacrolimus granules in whole blood on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
The correlation between Ctrough and AUCtau is assessed by Pearson's coefficient at each sample time by visit.
PK of tacrolimus granules in whole blood: Trough blood concentration (Ctrough) on Day 1
时间窗: Pre-dose on day 1
Ctrough is recorded from the PK blood samples collected.
Number of Participants with Treatment Emergent Adverse Events (AEs)
时间窗: From first dose to month 12
An AE is defined as any untoward medical occurrence in a participant given a study drug not necessarily linked to this treatment. An AE can be any unfavorable and unintended sign (e.g., abnormal laboratory finding; abnormal laboratory test result or other safety assessment, symptom, or disease) temporally associated with the use of study drug whether or not considered related to the study drug. Treatment emergent adverse event (TEAE) is defined as AE observed after administering the study drug.
PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 1
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Dose-normalized AUCtau is AUCtau normalized with the dose just prior to blood sampling. Dose-normalized AUCtau is calculated as AUCtau/dose.
Percentage of Participants With Biopsy-Proven Acute Rejections (BPAR)
时间窗: From first dose to month 12
AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection is performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies". A BPAR episode is defined as any AR episode confirmed by biopsy.
PK of granules tacrolimus in whole blood: Ctrough on Day 7
时间窗: Pre-dose on day 7
Ctrough is recorded from the PK blood samples collected.
Percentage of Participants With Acute Rejection (AR)
时间窗: From first dose to month 12
AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection is performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies".
PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Dose-normalized AUCtau is AUCtau normalized with the dose just prior to blood sampling. Dose-normalized AUCtau is calculated as AUCtau/dose.
PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 7
时间窗: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Ctrough normalized with the dose just prior to blood sampling. Dose-normalized Ctrough is calculated as Ctrough/dose.
Percentage of Participants With Clinically Suspected Rejection
时间窗: From first dose to month 12
AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection is performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies". An AR is clinically suspected in participants who experienced an increase in serum creatinine, after the exclusion of other causes of graft dysfunction (generally with biopsy).
次要结局
未报告次要终点