NCT00282568

Brief Summary

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

Trial Health

90
On Track

Trial Health Score

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

Enrollment
70

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2002

Longer than P75 for phase_2

Geographic Reach
2 countries

9 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

August 1, 2002

Completed
3.5 years until next milestone

First Submitted

Initial submission to the registry

January 25, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 27, 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

September 26, 2013

Completed
Last Updated

September 26, 2013

Status Verified

July 1, 2013

Enrollment Period

6.2 years

First QC Date

January 25, 2006

Results QC Date

July 25, 2013

Last Update Submit

July 25, 2013

Conditions

Kidney Transplantation

Keywords

PharmacokineticsTherapyImmunosuppressionDrugs, InvestigationalAdult

Outcome Measures

Primary Outcomes (6)

  • 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 trapezoidal rule.

    For tacrolimus, Days 1 and 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, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

  • Maximum Observed Concentration (Cmax) of Tacrolimus

    The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.

    For tacrolimus, Days 1 and 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, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

  • Minimum Concentration of Tacrolimus (Cmin)

    The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose.

    Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.

  • Time to Maximum Observed Concentration of Tacrolimus (Tmax)

    The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.

    For tacrolimus, Days 1 and 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, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

  • Patient Survival

    Patient Survival defined as any participant who did not die by the time of analysis.

    From enrollment until the end of study (up to 60 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 permanent return to dialysis (for more than 30 days)) or participants death.

    From enrollment until the end of study (up to 60 months).

Secondary Outcomes (15)

  • Percentage of Participants With Biopsy-confirmed Acute Rejection

    From enrollment until the end of study (up to 60 months).

  • Change From Baseline in Serum Creatinine

    Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).

  • Change From Baseline in Creatinine Clearance

    Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).

  • Time to Event for Patient Non Survival

    From enrollment until the end of study (up to 60 months).

  • Time to Event for Graft Non Survival

    From enrollment until the end of study (up to 60 months).

  • +10 more secondary outcomes

Study Arms (1)

Tacrolimus Modified Release

EXPERIMENTAL

Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.

Drug: Tacrolimus Modified Release (MR)Drug: tacrolimus

Interventions

Tacrolimus Modified Release (MR)DRUG

Oral

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

Oral

Also known as: Prograf®, FK506
Tacrolimus Modified Release

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient is currently receiving Prograf ® based immunosuppressive therapy for kidney 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 kidney
  • Patient is currently receiving sirolimus immunosuppression therapy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55455, United States

Location

Unknown Facility

Cincinnati, Ohio, 45267, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

Unknown Facility

Madison, Wisconsin, 53792, United States

Location

Unknown Facility

Milwaukee, Wisconsin, 53226, United States

Location

Unknown Facility

Edmonton, Alberta, T6G 2B7, Canada

Location

Unknown Facility

Toronto, Ontario, M5C 2T2, Canada

Location

Related Publications (2)

  • Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. Transplantation. 2007 Jun 27;83(12):1648-51. doi: 10.1097/01.tp.0000264056.20105.b4.

    PMID: 17589351BACKGROUND

  • Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen. Transplant Proc. 2005 Mar;37(2):867-70. doi: 10.1016/j.transproceed.2004.12.222.

    PMID: 15848559BACKGROUND

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 25, 2006

First Posted

January 27, 2006

Study Start

August 1, 2002

Primary Completion

October 1, 2008

Study Completion

October 1, 2008

Last Updated

September 26, 2013

Results First Posted

September 26, 2013

Record last verified: 2013-07

Locations

US(7)CA(2)