A 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

Study Overview
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Brief Summary
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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.

Detailed Description
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Pediatric participants will be treated with a Modigraf (tacrolimus granules) based immunosuppressive regimen for 12 months.

Official Title
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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

Conditions
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Liver Transplantation, Kidney Transplantation

Intervention / Treatment
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* Drug: Tacrolimus granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus granules (Modigraf)<br>Participants will receive the first dose of Modigraf in the morning within 24 hours after reperfusion. Total initial dose will be received in two divided doses post operatively. Subsequent oral Modigraf doses will be adjusted by the investigator and will be received in two doses (recommended interval 12 hours) | Drug: Tacrolimus granules<br>* Oral<br>* Other names: Modigraf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of tacrolimus in whole blood: area under the blood concentration - time curve for a dosing interval (AUCtau) | AUCtau will be recorded from the pharmacokinetic (PK) whole blood sample collected. | Up to 14 days | 
| Pharmacokinetics of tacrolimus in whole blood: maximum concentration (Cmax) | Cmax will be recorded from the PK whole blood sample collected. | Up to 14 days | 
| Pharmacokinetics of tacrolimus in whole blood: time to attain Cmax (tmax) | tmax will be recorded from the PK whole blood sample collected. | Up to 14 days | 
| Pharmacokinetics of tacrolimus in whole blood: blood concenration at the end of a dosing interval (Ctrough) | Ctrough will be recorded from the PK whole blood sample collected. | Up to 14 days | 
| Determine the correlation between Ctrough and AUCtau PK parameters | The correlation between Ctrough and AUCtau PK parameters will be assessed by Pearson's coefficient at each sample time. | up to 14 days | 
| Incidence of rejection episodes | The reporting of acute rejection includes any biopsy-proven or clinically suspected rejection of a participant after transplantation. | Up to 12 months | 
| Number of participant survivals | Participant survival status will be recorded during 12 months post-transplant. | Up to 12 months | 
| Number of graft survivals | Graft failure is defined as graft dysfunction, including re-transplantation or death. | Up to 12 months | 
| Number of dose changes throughout the study period | The number of dose changes will be recorded throughout the study period. | Up to 12 months | 
| Number of participants with Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not related to study drug. | Up to 12 months | 
| Number of participants with laboratory value abnormalities and/or adverse events (AEs) | Number of participants with potentially clinically significant laboratory values. | Up to 12 months | 
| Number of participants with vital sign abnormalities and/or adverse events (AEs) | Number of participants with potentially clinically significant vital sign values. | Up to 12 months | 
| Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events (AE) | Number of participants with potentially clinically significant ECG values. | Up to 12 months | 
| Assess levels of Tacrolimus whole blood trough using a local assay method | Tacrolimus whole blood trough levels will be routinely monitored using a local assay method, for example EMITÒ or Liquid-Chromatography-Mass-Spectrometry-Mass-Spectrometry (LC-MS-MS) in local laboratories. | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Transplantation, Kidney Transplantation, Modigraf, Tacrolimus, Pediatric, Pharmacokinetics