A Study 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

Astellas

Status and phase: Completed; Phase 2

Conditions: Liver Transplantation; Kidney Transplantation; Heart Transplantation

Treatments: Drug: Tacrolimus; Drug: Tacrolimus prolonged release

Study type: Interventional

Funder types: Industry

Identifiers

NCT01614665

PMR-EC-1207

2011-000078-80 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Part C: Continuation of long-term follow-up (from Day 365 onwards). Participants who have completed Part B and to whom continued treatment with Advagraf® is not currently available, will be offered participation in a continuation of long-term follow-up Part C. Part C will continue until Advagraf® becomes available to these participants or these participants' discontinuation, whichever is the earliest.

This applies to participants in the following countries: Czech Republic, Italy, UK and Poland only.

Enrollment: 44 patients

Sex: All

Ages: Under 15 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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44 participants in 2 patient groups

Tacrolimus

Active Comparator group

Description:

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.

Treatment:

Drug: Tacrolimus

Tacrolimus Prolonged Release

Experimental group

Description:

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.

Treatment:

Drug: Tacrolimus prolonged release