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
- Conditions
- Prophylaxis of heart, liver and kidney transplant rejection in paediatricsMedDRA version: 20.0Level: LLTClassification code 10050434Term: Prophylaxis against liver transplant rejectionSystem Organ Class: 100000004865MedDRA version: 20.0Level: LLTClassification code 10050436Term: Prophylaxis against renal transplant rejectionSystem Organ Class: 100000004865MedDRA version: 20.0Level: LLTClassification code 10050432Term: Prophylaxis against heart transplant rejectionSystem Organ Class: 100000004865Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2011-000078-80-PL
- Lead Sponsor
- Astellas Pharma Europe Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 44
1. The subject is aged < 16 years of age, undergoing primary liver, kidney or heart allograft transplantation.
2. The subject must be able to swallow intact Prograf® or Advagraf® capsules.
3. Female subjects of child bearing potential must provide a negative urine or serum pregnancy test prior to enrolment in the study.
4. Male and female subjects that are sexually active must agree to practice effective birth control during the study. (An effective method of birth control is defined as those which result in a low failure rate (ICH M3(R2)) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner).
5. The subject’s parent(s), or their legal representative(s), has been fully informed and has given written informed consent to participate in the study. The subject has given assent where applicable.
Additional Inclusion Criteria on Day 1 (Heart transplant subjects):
6. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 64
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Subject is receiving a multi-organ transplant or has previously received an organ transplant (including re-transplantation).
2. Subject with pulmonary vascular resistance =4 Wood units despite medication.
3. 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)
4. 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)
5. 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)
6. Subject with significant, uncontrolled concomitant infections and/or severe diarrhoea, vomiting, active upper gastrointestinal disorder that may affect the absorption of tacrolimus or active peptic ulcer.
7. Subject requiring systemic immunosuppressive medication for any other indication than transplantation.
8. Subject or donor known to be HIV or HCV or HBV positive.
9. Subject is allergic or intolerant to steroids, macrolide antibiotics, MMF or tacrolimus.
10. Subject is pregnant or breast-feeding.
11. Subject is unlikely to comply with the visits scheduled in the protocol.
12. Subject has any form of substance abuse, psychiatric disorder or condition which, in the opinion of the Investigator, may complicate communication with the Investigator.
13. Subject is participating or has participated in another clinical trial and/or those taking or having taken an investigational/non-registered drug in the past 28 days.
14. Subject is taking or requiring to be treated with medication or substances known to interfere with tacrolimus metabolism and listed in section below ‘Prohibited Concomitant Medication’ or having taken such medication within 28 days prior to inclusion.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the systemic exposure (AUC0-24h) of tacrolimus for Advagraf® versus Prograf® after the first dose and following repeated administration in pediatric subjects undergoing de novo allograft transplantation of kidney, liver or heart.;Secondary Objective: To observe the long-term safety and efficacy profile of tacrolimus for Advagraf® with that of Prograf® in pediatric subjects undergoing de novo allograft transplantation of kidney, liver or heart.;Primary end point(s): Primary Pharmacokinetic Variables<br>• The systemic exposure (AUC0-24h at each of Day 1, Day 7 and Day 28) of tacrolimus after first dose and under steady state conditions. Primary Safety Variables<br>• AEs<br>• Laboratory parameters<br>• Vital signs;Timepoint(s) of evaluation of this end point: AUC0-24h at each of Day 1, Day 7 and Day 28.<br>Long term safety at 2, 3, 6 and 12 months.
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: PK variables at Day 1, Day 7 and Day 28<br><br>Long term efficacy variables at 2, 3, 6 and 12 months.;Secondary end point(s): Secondary Pharmacokinetic Variables<br>The following PK parameters for tacrolimus will be determined for each profile<br>• Cmax<br>• tmax<br>• C24<br>Efficacy Variables<br>• Rejection episodes<br>• Subject and graft survival<br>