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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )
ClinicalTrials.gov Identifier:
NCT01614665
First received: June 6, 2012
Last updated: February 8, 2017
Last verified: February 2017
  Purpose

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 Intervention Phase
Heart Transplantation
Kidney Transplantation
Liver Transplantation
Drug: Prograf®
Drug: Advagraf
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

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

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

Enrollment: 44
Study Start Date: March 2012
Estimated Study Completion Date: November 2025
Estimated Primary Completion Date: November 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Prograf®
oral
Drug: Prograf®
Oral
Other Names:
  • tacrolimus
  • FK506
Experimental: Advagraf®
oral
Drug: Advagraf
oral
Other Names:
  • tacrolimus
  • prolonged release formulation
  • FK506E (MR4)

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 and Poland only.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01614665

Locations
Belgium
Site BE22
Leuven, Belgium, 3000
Czech Republic
Site CZ61
Prague 5, Czech Republic, 150 06
France
Site FR32
Paris Cedex 15, Necker, France
Site FR33
Bron Cedex, France, 69677
Italy
Site IT51
Bergamo, Italy, 24127
Site IT52
Rome, Italy, 00165
Poland
Site PL71
Warsaw, Poland, 04-730
Site PL72
Warsaw, Poland, 04-736
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, WC1N3JH
Site GB42
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Investigators
Study Director: Clinical Study Manager Astellas Pharma Europe Ltd.
  More Information

Responsible Party: Astellas Pharma Europe Ltd.
ClinicalTrials.gov Identifier: NCT01614665     History of Changes
Other Study ID Numbers: PMR-EC-1207  2011-000078-80 
Study First Received: June 6, 2012
Last Updated: February 8, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc:
Transplant
Prograf
Heart
Advagraf
Tacrolimus
Immunosuppression
Kidney
Liver
Pharmacokinetic
Pediatric

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

ClinicalTrials.gov processed this record on February 24, 2017