NCT00282256

Brief Summary

A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable pediatric liver transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2004

Longer than P75 for phase_2

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2004

Completed
2.1 years until next milestone

First Submitted

Initial submission to the registry

January 24, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 26, 2006

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2008

Completed
5 years until next milestone

Results Posted

Study results publicly available

October 17, 2013

Completed
Last Updated

October 17, 2013

Status Verified

August 1, 2013

Enrollment Period

4.8 years

First QC Date

January 24, 2006

Results QC Date

August 12, 2013

Last Update Submit

August 12, 2013

Conditions

Liver Transplantation

Keywords

ChildPharmacokineticsImmunosuppression DrugsHepatic transplantLiver Transplantation

Outcome Measures

Primary Outcomes (4)

  • Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus

    The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 and AUC 12-24 for the morning and afternoon doses.

    For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

  • Minimum Observed Concentration of Tacrolimus (Cmin)

    The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.

    Day 7 at 12 hours post-dose (tacrolimus) and Day 14 at 24 hours post-dose (tacrolimus MR).

  • Patient Survival

    Patient survival was defined as any participant known to be alive at the end of the study.

    From enrollment until the end of study (up to 54 months).

  • Graft Survival

    Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant) or participant death.

    From enrollment until the end of study (up to 54 months).

Secondary Outcomes (14)

  • Maximum Observed Concentration of Tacrolimus (Cmax)

    For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

  • Time to Maximum Observed Concentration of Tacrolimus (Tmax)

    For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

  • Percentage of Participants With Biopsy-confirmed Acute Rejection

    From enrollment until the end of study (up to 54 months).

  • Time to Event for Patient Non-survival

    From enrollment until the end of study (up to 54 months).

  • Time to Event for Graft Non-survival

    From enrollment until the end of study (up to 54 months).

  • +9 more secondary outcomes

Study Arms (1)

Tacrolimus MR

EXPERIMENTAL

Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.

Drug: tacrolimus modified release (MR)Drug: tacrolimus

Interventions

tacrolimus modified release (MR)DRUG

Oral

Also known as: Advagraf,, FK506E,, MR4,, FKMR,, Astagraf XL
Tacrolimus MR
tacrolimusDRUG

Oral

Also known as: Prograf,, FK506
Tacrolimus MR

Eligibility Criteria

AgeUp to 12 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Patient is currently receiving Prograf® based immunosuppressive therapy for liver transplantation.
  • Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable

You may not qualify if:

  • Patient has previously received an organ transplant other than a liver
  • Patient is currently receiving sirolimus immunosuppression therapy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Indianapolis, Indiana, 46202, United States

Location

Unknown Facility

New Orleans, Louisiana, 70433, United States

Location

Unknown Facility

New York, New York, 10029, United States

Location

Unknown Facility

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

  • Heffron TG, Pescovitz MD, Florman S, Kalayoglu M, Emre S, Smallwood G, Wisemandle K, Anania C, Dhadda S, Sawamoto T, Keirns J, Fitzsimmons W, First MR. Once-daily tacrolimus extended-release formulation: 1-year post-conversion in stable pediatric liver transplant recipients. Am J Transplant. 2007 Jun;7(6):1609-15. doi: 10.1111/j.1600-6143.2007.01803.x.

    PMID: 17511684BACKGROUND

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Limitations and Caveats

Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

Results Point of Contact

Title
Vice President, Therapeutic Area Head, Transplantation
Organization
Astellas Pharma Global Development, Inc.
ClinicalTrials.Disclosure@us.astellas.com

Study Officials

  • Central Contact

    Astellas Pharma US, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 24, 2006

First Posted

January 26, 2006

Study Start

January 1, 2004

Primary Completion

October 1, 2008

Study Completion

October 1, 2008

Last Updated

October 17, 2013

Results First Posted

October 17, 2013

Record last verified: 2013-08

Locations

US(5)