A study to determine the uptake, distribution and removal of the active ingredient tacrolimus from the body in children with newly transplanted organs after taking Modigraf (tacrolimus-containing medicine in the form of granules that can be suspended in fluid).

Phase 1

• Conditions: De novo allograft transplantation (liver, heart, kidney) in paediatric patients.; MedDRA version: 18.0Level: PTClassification code 10019314Term: Heart transplantSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 18.0Level: LLTClassification code 10023438Term: Kidney transplantSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 18.0Level: LLTClassification code 10024716Term: Liver transplantationSystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

• Registration Number: EUCTR2009-012258-19-FR
• Lead Sponsor: Astellas Pharma Europe Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-16
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. The subject is 12 years of age or younger.
2. The subject is the recipient of a solid organ (liver, kidney or heart) transplant. Multiorgan transplants are acceptable as long as one of the organs transplanted is liver, kidney or heart.
3. The subject’s parent(s) or their legal representative(s) has been fully informed and has given written informed consent to participate in the study. The subject has given assent where applicable.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. The subject has previously received another organ transplant (including liver, kidney or heart re-transplantation).
2. Subject has a high immunological risk, defined as a Panel Reactive Antibody (PRA)
score >50% in the previous 6 months (only applicable for renal transplant recipients).
3. Cold ischemia time of the donor kidney greater than 30 hours (only applicable for renal transplant recipients).
4. Subject receives an AB0 incompatible donor organ.
5. Subject has significant renal impairment, defined as having serum creatinine =230
µmol/l (=2.6 mg/dl) pre-transplantation (not applicable for renal transplant recipients).
6. Subject has significant liver disease, defined as having elevated ALT and/or AST and/or Total Bilirubin levels 3 times the upper value of the normal range during the 28 days prior to transplantation (not applicable for liver transplant recipients).
7. Subject with pulmonary vascular resistance greater than 4 Wood units which is
unresponsive to treatment.
8. Subjects with malignancies or a history of malignancy within the last 5 years.
9. Subject 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.
10. Subject requires systemic immunosuppressive medication for any indication other than transplantation.
11. Recipient or donor known to be HIV, HCV or HBV positive.
12. Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab or tacrolimus.
13. Subject is currently participating in another clinical trial and/or has been taking an
investigational drug in the 3 months prior to transplantation.
14. Subject is unlikely to comply with the visits scheduled in the protocol.
15. Subjects taking or requiring to be treated with medication or substances prohibited by this protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Day 1 and Day 7;Main Objective: To determine the pharmacokinetics (PK) of tacrolimus following oral administration of<br>Modigraf®, after the first oral dose and at steady state in paediatric subjects undergoing de novo allograft transplantation.;Secondary Objective: Safety and efficacy of Modigraf®. ;Primary end point(s): PK parameters for tacrolimus will be determined after the morning dose on<br>Day 1 and Day 7 (+7 days): <br>- AUCtau<br>- Cmax<br>- tmax<br>- Ctrough

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy:<br>• Rejection episodes<br>• Patient and graft survival<br>Safety:<br>• Incidence of adverse events<br>• Laboratory parameters<br>• Vital signs;Timepoint(s) of evaluation of this end point: Day 14 (end of study duration)