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

NCT01614665 | Completed Phase 2 DMC

• 2 other identifiers: PMR-EC-12072011-000078-80
• Study Type: interventional
• Target: 44
• Locations: 5 countries
• Sites: 10

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.

Conditions

Heart Transplantation; Kidney Transplantation; Liver Transplantation

Keywords

Transplant; Prograf; Heart; Advagraf; Tacrolimus; Immunosuppression; Kidney; Liver; Pharmacokinetic; Pediatric

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus (Part A)

  Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose

• Number of Participants with Adverse Events (Part A + B)

  Safety is assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important.

  From first dose of study drug up to 7 days after last dose of study drug in Part B (up to 53 weeks)

• Number of Participants with Adverse Events (Part C)

  Safety is assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important.

  Up to 9 years

Secondary Outcomes (11)

• Maximum Concentration (Cmax) of Tacrolimus (Part A)

  Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose

• Time to Attain Maximum Concentration (tmax) of Tacrolimus (Part A)

  Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose

• Trough Concentration (C12) for Tacrolimus (Part A)

  Days 1, 7 and 28, 12 hours after dosing

• Trough Concentration (C24) for Tacrolimus (Part A)

  Days 1, 7 and 28, 24 hours after dosing

• Correlation between AUC24 & C24 (Part A)

  Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

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

Drug: Tacrolimus

Tacrolimus Prolonged Release

EXPERIMENTAL

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 and of the study.

Drug: Tacrolimus prolonged release

Interventions

Tacrolimus DRUG

Participants receive an initial total daily dose of tacrolimus depending on the type of organ transplant (heart = 0.075 mg/kg; liver/kidney = 0.3 mg/kg), to be given orally (or via nasogastric tube for liver transplant recipients) in 2 doses in the morning and the evening. The first dose is administered in the morning within days of skin closure (heart = 4 days; liver = 2 days; kidney = within 24 hours following reperfusion). Subsequent tacrolimus doses are taken orally twice a day in the morning and evening and are adjusted on the basis of clinical evidence of efficacy, occurrence of adverse events and observing the recommended whole blood trough level ranges (day 1 through 21 = 10 to 20 ng/mL; day 22 through 365 = 5 to 15 ng/mL).

Also known as: Prograf, FK506

Tacrolimus

Tacrolimus prolonged release DRUG

Participants receive an initial total daily dose of tacrolimus prolonged release depending on the type of organ transplant (heart = 0.075 mg/kg; liver/kidney = 0.3 mg/kg), to be given orally (or via nasogastric tube for liver transplant recipients) in 1 dose. The first dose is administered in the morning within days of skin closure (heart = 4 days; liver = 2 days; kidney = within 24 hours following reperfusion). Subsequent tacrolimus prolonged release doses are taken orally once a day in the morning and are adjusted on the basis of clinical evidence of efficacy, occurrence of adverse events and observing the recommended whole blood trough level ranges (day 1 through 21 = 10 to 20 ng/mL; day 22 through 365 = 5 to 15 ng/mL).

Also known as: Prograf XL, Graceptor, FK506 (MR4), Advagraf, Astagraf XL

Tacrolimus Prolonged Release

Eligibility Criteria

• Age: Up to 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Europe Ltd.: lead

Study Sites (10)

Site CZ61

Prague, 150 06, Czechia

Location

Site FR33

Bron, 69677, France

Location

Site FR32

Paris, France

Location

Site IT52

Rome, 00165, Italy

Location

Site PL71

Warsaw, 04-730, Poland

Location

Site GB43

Birmingham, B4 6NH, United Kingdom

Location

Site GB46

Liverpool, L12 2AP, United Kingdom

Location

Site GB44

London, SE5 9RS, United Kingdom

Location

Site GB45

London, WC1 3JH, United Kingdom

Location

Site GB42

Manchester, M13 9WL, United Kingdom

Location

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website.
• Link to plain language summary of the study on the Trial Results Summaries website.

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Clinical Study Manager

  Astellas Pharma Europe Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 8, 2012
• Study Start: April 3, 2012
• Primary Completion: April 21, 2021
• Study Completion: April 21, 2021
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); IT (1); CZ (1); FR (2); GB (5)