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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01294020
First Posted: February 11, 2011
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )
  Purpose
Conversion of stable pediatric allograft recipients from Prograf® immunosuppression to Advagraf® immunosuppression to compare exposure and follow for safety and efficacy over one year.

Condition Intervention Phase
Intestine Transplantation Kidney Transplantation Lung Transplantation Liver Transplantation Heart Transplantation Drug: Tacrolimus Drug: Tacrolimus prolonged release Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Europe Ltd. ):

Primary Outcome Measures:
  • Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus and Tacrolimus Prolonged Release [ Time Frame: 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 Outcome Measures:
  • Maximum Concentration (Cmax) of Tacrolimus and Tacrolimus Prolonged Release [ Time Frame: 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 ]
  • Time to Attain Maximum Concentration (tmax) of Tacrolimus and Tacrolimus Prolonged Release [ Time Frame: 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 ]
  • Trough Concentration (C24) for Tacrolimus and Tacrolimus Prolonged Release [ Time Frame: Days 7 and 14, 24 hours after dosing ]
  • Trough Concentration (C12) for Tacrolimus [ Time Frame: Day 7, 12 hours after dosing ]
  • Number of Participants with Acute Rejections [ Time Frame: Up to Week 54 ]
    Rejection episodes/acute rejections are indicated by clinical and/or laboratory signs, and are classified according to their rejection specific treatment: •Spontaneously Resolving Acute Rejection: not treated with new or increased corticosteroid medication, antibodies or any other medication and resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Sensitive Acute Rejection: treated with new or increased corticosteroid medication only and which has resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Resistant Acute Rejection: did not resolve following treatment with corticosteroids; - Resolved with further treatment: any acute rejection with an end date AND a treatment other than corticosteroid used; - Unresolved with further treatment: any acute rejection with no end date AND a treatment other than corticosteroid used; - Unresolved with no further treatment: any acute rejection with no end date AND ONLY corticosteroid treatment was used.

  • Number of Participants with Biopsy Proven Acute Rejections (BPARs) [ Time Frame: Up to Week 54 ]
    BPAR episodes are defined as acute rejection episodes confirmed by biopsy, and are classified according to their rejection specific treatment: •Spontaneously Resolving Acute Rejection: not treated with new or increased corticosteroid medication, antibodies or any other medication and resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Sensitive Acute Rejection: treated with new or increased corticosteroid medication only and which has resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Resistant Acute Rejection: did not resolve following treatment with corticosteroids; - Resolved with further treatment: any acute rejection with an end date AND a treatment other than corticosteroid used; - Unresolved with further treatment: any acute rejection with no end date AND a treatment other than corticosteroid used; - Unresolved with no further treatment: any acute rejection with no end date AND ONLY corticosteroid treatment used.

  • Severity of Biopsy Proven Acute Rejection Episodes [ Time Frame: Up to Week 54 ]
    The severity of BPARs is categorized with specific criteria by organ: For kidney transplant participants, according to Banff '97 Diagnostic categories for renal allograft biopsies - Banff '07 update (Acute antibody-mediated rejection I, II, and III, Acute T cell mediated rejection IA, IB, IIA, IIB and III); for liver transplant participants, according to 1997 Banff Schema for grading of Liver Allograft Rejection (mild, moderate, severe or indeterminate/borderline); for heart, according to Standardized Nomenclature of the International Society of Heart and Lung Transplantation (mild, moderate, severe).

  • Patient survival [ Time Frame: Up to Week 54 ]
    Patient survival is defined as the time from first dose of tacrolimus as study drug to the date of death from any cause

  • Graft survival [ Time Frame: Up to Week 54 ]
    Graft survival is defined as the time from the first dose of tacrolimus as study drug to graft loss. Graft loss is defined as retransplantation, nephrectomy (in case of kidney transplantation), death or dialysis (in case of kidney transplantation) ongoing at end of study or at discontinuation, unless superseded by follow-up information.

  • Efficacy Failure [ Time Frame: Up to Week 54 ]
    Efficacy failure is defined as the composite of the following: death, graft loss, BPAR and unknown outcome.

  • Number of Participants with Adverse Events (Part A) [ Time Frame: From first dose of tacrolimus up to 7 days after last dose of tacrolimus prolonged release in Part A (up to 21 days) ]
    Safety as assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was 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, required or prolonged hospitalization or is considered medically important.

  • Number of Participants with Adverse Events (Part B) [ Time Frame: 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) ]
    Safety as assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was 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, required or prolonged hospitalization or is considered medically important.


Enrollment: 81
Actual Study Start Date: May 25, 2011
Estimated Study Completion Date: May 2026
Primary Completion Date: October 25, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tacrolimus Prolonged Release
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.
Drug: Tacrolimus
Oral capsule
Other Names:
  • Prograf
  • FK506
Drug: Tacrolimus prolonged release
Oral capsule
Other Names:
  • FK506E
  • MR4
  • Advagraf
  • tacrolimus modified release
  • Astagraf XL
  • Graceptor
  • Prograf XL

Detailed Description:

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.

This applies to patients in the following countries: Czech Republic, Germany, Italy and Poland only.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   5 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01294020


Locations
Belgium
Site BE21
Brussels, Belgium, 1020
Site BE22
Brussels, Belgium, 1200
Czechia
Site CZ42
Prague 5, Czechia, 150 06
France
Site FR34
Bron Cedex, France, 69677
Site FR35
BRON Cedex, France, 69677
Site FR31
Paris Cedex 15, France, 75743
Site FR32
Paris Cedex 15, France, 75743
Site FR33
Paris Cedex 15, France, 75908
Germany
Site DE41
Heidelberg, Germany, 69120
Italy
Site IT74
Bergamo, Italy, 24127
Site IT75
Palermo, Italy, 90127
Poland
Site PL51
Warsaw, Poland, 04-730
Site PL52
Warsaw, Poland, 04-730
United Kingdom
Site GB62
Birmingham, United Kingdom, B4 6NH
Site GB64
London, United Kingdom, WC1 3JH
Site GB61
Manchester, United Kingdom, M27 4HA
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Investigators
Study Chair: Use Central Contact Astellas Pharma Europe Ltd.
  More Information

Additional Information:
Responsible Party: Astellas Pharma Europe Ltd.
ClinicalTrials.gov Identifier: NCT01294020     History of Changes
Other Study ID Numbers: PMR-EC-1206
2010-020925-42 ( EudraCT Number )
First Submitted: February 3, 2011
First Posted: February 11, 2011
Last Update Posted: December 7, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe Ltd. ):
Transplant
Liver
Tacrolimus
Kidney
Heart
Lung
Immunosuppression
Advagraf
Pharmacokinetics

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action