Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From Prograf® to Advagraf®

Astellas

Status and phase: Completed; Phase 2

Conditions: Liver Transplantation; Kidney Transplantation; Lung Transplantation; Heart Transplantation; Intestine Transplantation

Treatments: Drug: Tacrolimus; Drug: Tacrolimus prolonged release

Study type: Interventional

Funder types: Industry

Identifiers

NCT01294020

2024-517571-20-00 (Registry Identifier)

PMR-EC-1206

2010-020925-42 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 81 patients

Sex: All

Ages: 5 to 16 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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81 participants in 1 patient group

Tacrolimus Prolonged Release

Experimental group

Description:

Participants receive tacrolimus prolonged release once daily starting from day 1 for 4 weeks for in Part A, and continue to receive tacrolimus prolonged release once daily up to end of Part B of the study.

Treatment:

Drug: Tacrolimus prolonged release

Drug: Tacrolimus