Clinical trial NCT01371331: A Study to Determine Pharmacokinetics of Children Receiving Modigraf (Tacrolimus Granules) Following Solid Organ Transplantation
Official title: A Multicentre, Open-label, Pharmacokinetic Study of Modigraf® (Tacrolimus Granules) in de Novo Paediatric Allograft Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Heart Transplantation
Liver Transplantation
Keywords: Kidney Transplantation
Pharmacokinetics
Heart Transplantation
Liver Transplantation
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-06-10
Enrollment: 52
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to find out how much of Modigraf is absorbed and used in the body and how fast it leaves the body (Pharmacokinetics). The results will then help to decide how much Modigraf in future can be given safely to children and young people following transplantation.

Detailed description: The primary objective of this study is to determine the pharmacokinetics (PK) of tacrolimus following oral administration of Modigraf, after the first oral dose and at steady state in paediatric subjects undergoing de novo allograft transplantation.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* The subject has previously received another organ transplant (including liver, kidney or heart re-transplantation)
* 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)
* Cold ischemia time of the donor kidney greater than 30 hours (only applicable for renal transplant recipients)
* Subject receives an AB0 incompatible donor organ
* 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)
* Subject has significant liver disease, defined as having elevated Alanine Aminotransferase (ALT) and/or Asparate Aminotransferase (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)
* Subject with pulmonary vascular resistance greater than 4 Wood units which is unresponsive to treatment
* Subjects with malignancies or a history of malignancy within the last 5 years
* 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
* Subject requires systemic immunosuppressive medication for any indication other than transplantation
* Recipient or donor known to be HIV, HCV or HBV positive
* Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab or tacrolimus
* Subject is currently participating in another clinical trial and/or has been taking an investigational drug in the 3 months prior to transplantation
* Subject is unlikely to comply with the visits scheduled in the protocol
* Subjects taking or requiring to be treated with medication or substances prohibited by this protocol

Primary outcomes:
measure: Determine AUCtau (area under the plasma concentration-time curve for a dosing interval)
timeFrame: on Day 1 and Day 7 (+/- 7 days)
measure: Determine Cmax (maximum concentration)
timeFrame: on Day 1 and Day 7 (+/- 7 days)
measure: Determine tmax (time to attain Cmax)
timeFrame: on Day 1 and Day 7 (+/- 7 days)
measure: Determine Ctrough (plasma concentration at the end of a dosing interval)
timeFrame: on Day 1 and Day 7 (+/- 7 days)
Secondary outcomes:
measure: Rejection episodes
timeFrame: 14 days
measure: Patient survival
timeFrame: 14 days
measure: Graft survival
timeFrame: 14 days
measure: Assessment of safety through the evaluation of Adverse Events, laboratory parameters and vital signs
timeFrame: 14 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Site 40
city: Bron Cedex
country: France
facility: Site: 60
city: Hannover
country: Germany
facility: Site 31
city: Heidelberg
country: Germany
facility: Site 30
city: Warsaw
country: Poland
facility: Site 50
city: Madrid
country: Spain
facility: Site 22
city: Madrid
country: Spain
facility: Site 20
city: Madrid
country: Spain
facility: Site 21
city: Birmingham
country: United Kingdom
facility: Site 10
city: Manchester
country: United Kingdom
facility: Site 13
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Senior Study Manager
role: STUDY_CHAIR
References:
citation: Webb NJA, Baumann U, Camino M, Frauca E, Undre N; OPTION Study Group. Pharmacokinetics of tacrolimus granules in pediatric de novo liver, kidney, and heart transplantation: The OPTION study. Pediatr Transplant. 2019 Feb;23(1):e13328. doi: 10.1111/petr.13328. Epub 2019 Jan 21.