A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Kidney Transplant Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00282568
First received: January 25, 2006
Last updated: July 25, 2013
Last verified: July 2013
Results First Received: July 25, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Kidney Transplantation
Interventions: Drug: Tacrolimus Modified Release (MR)
Drug: tacrolimus

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Stable, adult kidney transplant recipients being treated with tacrolimus (Prograf)-based immunosuppressive regimen.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Pharmacokinetic (PK) treatment period was from Day 1 - 35. Participants who completed the PK period were eligible to continue receiving tacrolimus MR in the extended treatment period, from Day 36 up to 60 months.

Reporting Groups
  Description
Tacrolimus Modified Release 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.

Participant Flow for 2 periods

Period 1:   Pharmacokinetic Treatment Period
    Tacrolimus Modified Release  
STARTED     70  
Received Tacrolimus     68  
Received Tacrolimus MR     67  
COMPLETED     67  
NOT COMPLETED     3  
Discontinued prior to Day 1                 2  
Enrolled erroneously                 1  

Period 2:   Extended Treatment Period
    Tacrolimus Modified Release  
STARTED     66 [1]
COMPLETED     42  
NOT COMPLETED     24  
Adverse Event                 17  
Non-compliance                 4  
Physician Decision                 1  
Lost to Follow-up                 2  
[1] One patient who completed the PK period did not enter the extended treatment period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable set defined as all patients with all five complete pharmacokinetic profiles (two tacrolimus and three tacrolimus MR).

Reporting Groups
  Description
Tacrolimus Modified Release 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.

Baseline Measures
    Tacrolimus Modified Release  
Number of Participants  
[units: participants]
  66  
Age  
[units: years]
Mean ± Standard Deviation
  46.9  ± 12.37  
Gender  
[units: participants]
 
Female     24  
Male     42  
Race/Ethnicity, Customized  
[units: participants]
 
White     53  
Black     12  
Asian     1  
Reason for End Stage Renal Disease  
[units: participants]
 
Glomerulonephritis     16  
Polycystic Kidney Disease     8  
Hypertensive Nephrosclerosis     6  
Immunoglobulin A Nephropathy     6  
Diabetes     6  
Systemic Lupus Erythematosis     5  
Focal Segmental Glomerulonephritis     5  
Tubular and Interstitial Disease     3  
Unknown     1  
Other     10  
Type of Current Transplant  
[units: participants]
 
Cadaver     43  
Living Related Donor     18  
Living Nonrelated Donor     5  
Re-transplant  
[units: participants]
 
No     61  
Yes     5  
History of Pre-Study Dialysis  
[units: participants]
 
No     12  
Yes     54  



  Outcome Measures
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1.  Primary:   Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus   [ Time Frame: 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. ]

2.  Primary:   Maximum Observed Concentration (Cmax) of Tacrolimus   [ Time Frame: 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. ]

3.  Primary:   Minimum Concentration of Tacrolimus (Cmin)   [ Time Frame: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose. ]

4.  Primary:   Time to Maximum Observed Concentration of Tacrolimus (Tmax)   [ Time Frame: 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. ]

5.  Primary:   Patient Survival   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

6.  Primary:   Graft Survival   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

7.  Secondary:   Percentage of Participants With Biopsy-confirmed Acute Rejection   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

8.  Secondary:   Change From Baseline in Serum Creatinine   [ Time Frame: 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). ]

9.  Secondary:   Change From Baseline in Creatinine Clearance   [ Time Frame: 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). ]

10.  Secondary:   Time to Event for Patient Non Survival   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

11.  Secondary:   Time to Event for Graft Non Survival   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

12.  Secondary:   Time to First Biopsy-confirmed Acute Rejection   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

13.  Secondary:   Grade of Biopsy-confirmed Acute Rejection Episodes   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

14.  Secondary:   Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

15.  Secondary:   Number of Participants With Multiple Rejection Episodes   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

16.  Secondary:   Number of Participants With Clinically Treated Acute Rejection Episodes   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

17.  Secondary:   Number of Participants With Chronic Rejection   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

18.  Secondary:   Number of Participants With Treatment Failure   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

19.  Secondary:   Primary Reason for Graft Loss   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

20.  Secondary:   Number of Participants Returning to Permanent Dialysis   [ Time Frame: From enrollment until the end of study (up to 60 months). ]

21.  Secondary:   Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs   [ Time Frame: From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Therapeutic Area Head, Transplantation
Organization: Astellas Pharma Global Development, Inc.
e-mail: ClinicalTrials.Disclosure@us.astellas.com


Publications:

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00282568     History of Changes
Other Study ID Numbers: 02-0-131
Study First Received: January 25, 2006
Results First Received: July 25, 2013
Last Updated: July 25, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada