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 currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Astellas Pharma Inc
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )
ClinicalTrials.gov Identifier:
NCT01614665
First received: June 6, 2012
Last updated: March 11, 2014
Last verified: March 2014
  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
Kidney Transplantation
Liver Transplantation
Heart Transplantation
Drug: Prograf®
Drug: Advagraf
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part A: Determine Cmax (maximum concentration) [ Time Frame: Day 1, Day 7 and Day 28 ] [ Designated as safety issue: No ]
  • Part A: Determine Tmax (time to attain Cmax) [ Time Frame: Day 1, Day 7 and Day 28 ] [ Designated as safety issue: No ]
  • Part A: Determine C24 (concentration prior to morning dose) [ Time Frame: Day 1, Day 7 and Day 28 ] [ Designated as safety issue: No ]
  • Part A & B: Rejection episodes [ Time Frame: Up to 1 year (End of study) ] [ Designated as safety issue: No ]
  • Part A & B: Subject and graft survival [ Time Frame: Up to 1 year (End of study) ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: March 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Prograf® Drug: Prograf®
Oral
Other Names:
  • tacrolimus
  • FK506
Experimental: Advagraf® 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.

  Eligibility

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
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

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

Contacts
Contact: Medical Affairs Europe + 44 1784 419400 contact@nl.astellas.com

Locations
Austria
Vienna General Hospital (AKH)/11 Withdrawn
Vienna, Austria
Belgium
K.U.Leuven/22 Recruiting
Leuven, Belgium
Czech Republic
University Hospital Motol/61 Recruiting
Prague, Czech Republic
France
Necker-Enfants Malades Hospital/32 Not yet recruiting
Paris, Necker, France
Italy
Ospedali Riuniti di Bergamo/51 Recruiting
Bergamo, Italy
Ospedale Bambin Gesu/52 Recruiting
Rome, Italy
Poland
Children's Memorial Health Institute/71 Recruiting
Warsaw, Poland
Children's Memorial Health Institute/72 Recruiting
Warsaw, Poland
Silesian Center for Heart Disease/73 Withdrawn
Zabrze, Poland
United Kingdom
Birmingham Children's Hospital/43 Recruiting
Birmingham, United Kingdom
Great Ormond Street Hospital/41 Not yet recruiting
London, United Kingdom
Great Ormond Street Hospital/ 45 Not yet recruiting
London, United Kingdom
Kings College Hospital/ 44 Withdrawn
London, United Kingdom
Royal Manchester Children's Hospital/42 Recruiting
Manchester, United Kingdom
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Investigators
Study Director: Clinical Study Manager Astellas Pharma Europe Ltd.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( 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: March 11, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014