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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01614665
Recruitment Status : Active, not recruiting
First Posted : June 8, 2012
Last Update Posted : December 21, 2017
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Heart Transplantation Kidney Transplantation Liver Transplantation Drug: Tacrolimus Phase 2

Detailed Description:

Subjects 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.

Subjects 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). Patients 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 patients or these patients' discontinuation, whichever is the earliest.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase II, Parallel Group, Randomized, Multicentre, Open Label Study to Compare the Pharmacokinetics of Tacrolimus in De Novo Pediatric Allograft Recipients Treated With an Advagraf® or Prograf® Based Immunosuppressive Regimen, Including a Long-Term Follow-Up
Actual Study Start Date : April 3, 2012
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Active Comparator: Prograf®
Drug: Tacrolimus
Other Names:
  • Advagraf
  • prolonged release formulation
  • Prograf
  • FK506E (MR4)

Experimental: Advagraf®
Drug: Tacrolimus
Other Names:
  • Advagraf
  • prolonged release formulation
  • Prograf
  • FK506E (MR4)

Primary Outcome Measures :
  1. Part A: Determine steady state systemic exposure (AUC0-24h) [ Time Frame: Day 1, Day 7 and Day 28 ]
  2. Part A & B: Assessment of safety through the evaluation of adverse events, laboratory parameters and vital signs [ Time Frame: Up to 1 year ]
  3. Part C: Assessment of safety through evaluation of adverse events [ Time Frame: Up to 9 years ]

Secondary Outcome Measures :
  1. Part A: Determine Cmax (maximum concentration) [ Time Frame: Day 1, Day 7 and Day 28 ]
  2. Part A: Determine Tmax (time to attain Cmax) [ Time Frame: Day 1, Day 7 and Day 28 ]
  3. Part A: Determine C24 (concentration prior to morning dose) [ Time Frame: Day 1, Day 7 and Day 28 ]
  4. Part A & B: Rejection episodes [ Time Frame: Up to 1 year (End of study) ]
  5. Part A & B: Subject and graft survival [ Time Frame: Up to 1 year (End of study) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01614665

Site CZ61
Prague 5, Czechia, 150 06
Site FR33
Bron Cedex, France, 69677
Site FR32
Paris Cedex 15, France
Site IT52
Rome, Italy, 00165
Site PL71
Warsaw, Poland, 04-730
United Kingdom
Site GB43
Birmingham, United Kingdom, B4 6NH
Site GB46
Liverpool, United Kingdom, L12 2AP
Site GB44
London, United Kingdom, SE5 9RS
Site GB45
London, United Kingdom, WC1 3JH
Site GB42
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Study Director: Clinical Study Manager Astellas Pharma Europe Ltd.

Responsible Party: Astellas Pharma Europe Ltd. Identifier: NCT01614665     History of Changes
Other Study ID Numbers: PMR-EC-1207
2011-000078-80 ( EudraCT Number )
First Posted: June 8, 2012    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe Ltd. ):

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action