Clinical trial NCT01294020: Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From Prograf® to Advagraf®
Official title: A Phase II, Open-Label, Multi-Center Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From a Prograf® Based Immunosuppressive Regimen to a Tacrolimus Prolonged Release, Advagraf® Based Immunosuppressive Regimen, Including a Long-Term Follow-Up
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Intestine Transplantation
Kidney Transplantation
Lung Transplantation
Liver Transplantation
Heart Transplantation
Keywords: Transplant
Liver
Tacrolimus
Kidney
Heart
Lung
Immunosuppression
Advagraf
Pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-02-11
Enrollment: 81
Sex: ALL
Minimum age (years): 5
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Parts A \& B: Conversion of stable pediatric allograft recipients from Prograf® immunosuppression to Advagraf® immunosuppression to compare exposure and one year follow-up for safety and efficacy.

Part C: Continuation of long-term follow-up and provision of ongoing study medication to subjects to whom Advagraf® is currently not available.

Detailed description: Part A: On Day 1 subjects will be converted from their routine Prograf®-based immunosuppressive regimen to a Prograf®-based immunosuppressive regimen supplied by the Sponsor as study medication and continue treatment until Day 7. The daily dose of the study medication must be the same \[1:1 (mg:mg)\] as the Prograf® dose received during the 30-day screening period.

On Day 7 the first 24 hour PK profile will be started. Samples will be taken over a 24 hour period and will be completed on Day 8.

On Day 8 subjects will be switched to once-daily Advagraf® on a 1:1 (mg:mg) total daily dose basis and continue treatment until Day 14.

On Day 14 the second 24-hour PK profile will be started. Samples will be taken over a 24-hour period and will be completed on Day 15.

Part B: One year follow-up period to evaluate safety and efficacy of tacrolimus when administered as an Advagraf®-based immunosuppressive regimen.

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.

Part C applies to patients in the following countries: United Kingdom, Czech Republic, Germany, Italy, and Poland only.

Eligibility criteria: Inclusion Criteria:

* Must be able to swallow intact study medication capsules
* Received a single solid organ transplant at least 6 months prior to entry into the study
* 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
* Has been receiving a Prograf® based immunosuppressive regimen for a minimum of 3 months
* Negative pregnancy test prior to enrolment (females)
* Must agree to practice effective birth control during the study
* Stable whole blood trough levels of tacrolimus in the range of 3.5 - 15ng/mL (+/-0.5ng/mL) and clinically stable in the opinion of the Investigator

Exclusion Criteria:

* Previously received a multiple organ transplant
* Any rejection episode within 3 months prior to enrolment or within the last 6 months that required anti-lymphocyte antibody therapy, or 2 or more rejection episodes within the last 12 months
* Currently receiving Rapamycin, Certican or MPA (Myfortic®)
* Chronic dysfunction of the allograft, in the opinion of the Investigator
* Major changes in their immunosuppressive regimen within the last 3 months prior to entry into the study
* The subject is pregnant or breast feeding

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus and Tacrolimus Prolonged Release
timeFrame: Day 7 (for tacrolimus) and day 14 (for tacrolimus prolonged release) at predose and 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
Secondary outcomes:
measure: Maximum Concentration (Cmax) of Tacrolimus and Tacrolimus Prolonged Release
timeFrame: Day 7 (for tacrolimus) and day 14 (for tacrolimus prolonged release) at predose and 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
measure: Time to Attain Maximum Concentration (tmax) of Tacrolimus and Tacrolimus Prolonged Release
timeFrame: Day 7 (for tacrolimus) and day 14 (for tacrolimus prolonged release) at predose and 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose
measure: Trough Concentration (C24) for Tacrolimus and Tacrolimus Prolonged Release
timeFrame: Days 7 and 14, 24 hours after dosing
measure: Number of Participants with Acute Rejections
timeFrame: Up to Week 54
measure: Number of Participants with Biopsy Proven Acute Rejections (BPARs)
timeFrame: Up to Week 54
measure: Severity of Biopsy Proven Acute Rejection Episodes
timeFrame: Up to Week 54
measure: Patient survival
timeFrame: Up to Week 54
measure: Graft survival
timeFrame: Up to Week 54
measure: Efficacy Failure
timeFrame: Up to Week 54
measure: Number of Participants with Adverse Events (Part A)
timeFrame: From first dose of tacrolimus up to 7 days after last dose of tacrolimus prolonged release in Part A (up to 21 days)
measure: Number of Participants with Adverse Events (Part B)
timeFrame: From first dose of tacrolimus prolonged release in Part A up to 7 days after last dose of tacrolimus prolonged release in Part B (up to 55 weeks)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Site BE21
city: Brussels
country: Belgium
facility: Site BE22
city: Prague 5
country: Czechia
facility: Site CZ42
city: Bron Cedex
country: France
facility: Site FR34
city: BRON Cedex
country: France
facility: Site FR35
city: Paris Cedex 15
country: France
facility: Site FR31
city: Paris Cedex 15
country: France
facility: Site FR32
city: Paris Cedex 15
country: France
facility: Site FR33
city: Heidelberg
country: Germany
facility: Site DE41
city: Bergamo
country: Italy
facility: Site IT74
city: Palermo
country: Italy
facility: Site IT75
city: Warsaw
country: Poland
facility: Site PL51
city: Warsaw
country: Poland
facility: Site PL52
city: Birmingham
country: United Kingdom
facility: Site GB62
city: London
country: United Kingdom
facility: Site GB64
city: Manchester
country: United Kingdom
facility: Site GB61
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Use Central Contact
role: STUDY_CHAIR
References: