Clinical trial NCT01614665: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Transplantation
Kidney Transplantation
Liver Transplantation
Keywords: Transplant
Prograf
Heart
Advagraf
Tacrolimus
Immunosuppression
Kidney
Liver
Pharmacokinetic
Pediatric
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-06-08
Enrollment: 44
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus (Part A)
timeFrame: Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
measure: Number of Participants with Adverse Events (Part A + B)
timeFrame: From first dose of study drug up to 7 days after last dose of study drug in Part B (up to 53 weeks)
measure: Number of Participants with Adverse Events (Part C)
timeFrame: Up to 9 years
Secondary outcomes:
measure: Maximum Concentration (Cmax) of Tacrolimus (Part A)
timeFrame: Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
measure: Time to Attain Maximum Concentration (tmax) of Tacrolimus (Part A)
timeFrame: Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
measure: Trough Concentration (C12) for Tacrolimus (Part A)
timeFrame: Days 1, 7 and 28, 12 hours after dosing
measure: Trough Concentration (C24) for Tacrolimus (Part A)
timeFrame: Days 1, 7 and 28, 24 hours after dosing
measure: Correlation between AUC24 & C24 (Part A)
timeFrame: Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
measure: Number of Participants with Acute Rejections (Part A + B)
timeFrame: Up to Week 52
measure: Number of Participants with Biopsy-proven Acute Rejection Episodes (BPARs) (Part A + B)
timeFrame: Up to Week 52
measure: Severity of Biopsy Proven Acute Rejection Episodes (Part A + B)
timeFrame: Up to Week 52
measure: Patient Survival (Part A + B)
timeFrame: Up to Week 52
measure: Graft Survival (Part A + B)
timeFrame: Up to Week 52
measure: Efficacy Failure (Part A + B)
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Prague 5
country: Czechia
facility: Site CZ61
city: Bron Cedex
country: France
facility: Site FR33
city: Paris Cedex 15
country: France
facility: Site FR32
city: Rome
country: Italy
facility: Site IT52
city: Warsaw
country: Poland
facility: Site PL71
city: Birmingham
country: United Kingdom
facility: Site GB43
city: Liverpool
country: United Kingdom
facility: Site GB46
city: London
country: United Kingdom
facility: Site GB44
city: London
country: United Kingdom
facility: Site GB45
city: Manchester
country: United Kingdom
facility: Site GB42
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Clinical Study Manager
role: STUDY_DIRECTOR
References: