Clinical trial NCT00282568: A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Kidney Transplant Patients
Official title: A Phase 2, Open-Label, Multi-center Study to Assess the Pharmacokinetics, Safety and Tolerability of Tacrolimus in Stable Kidney Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplantation
Keywords: Pharmacokinetics
Therapy
Immunosuppression
Drugs, Investigational
Adult
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2006-01-27
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Detailed description: This is a Phase II open-label, multi-center conversion study in stable, adult kidney transplant recipients 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
timeFrame: 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.
measure: Maximum Observed Concentration (Cmax) of Tacrolimus
timeFrame: 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.
measure: Minimum Concentration of Tacrolimus (Cmin)
timeFrame: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.
measure: Time to Maximum Observed Concentration of Tacrolimus (Tmax)
timeFrame: 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.
measure: Patient Survival
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Graft Survival
timeFrame: From enrollment until the end of study (up to 60 months).
Secondary outcomes:
measure: Percentage of Participants With Biopsy-confirmed Acute Rejection
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Change From Baseline in Serum Creatinine
timeFrame: 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).
measure: Change From Baseline in Creatinine Clearance
timeFrame: 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).
measure: Time to Event for Patient Non Survival
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Time to Event for Graft Non Survival
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Time to First Biopsy-confirmed Acute Rejection
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Grade of Biopsy-confirmed Acute Rejection Episodes
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Number of Participants With Multiple Rejection Episodes
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Number of Participants With Clinically Treated Acute Rejection Episodes
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Number of Participants With Chronic Rejection
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Number of Participants With Treatment Failure
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Primary Reason for Graft Loss
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Number of Participants Returning to Permanent Dialysis
timeFrame: From enrollment until the end of study (up to 60 months).
measure: Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs
timeFrame: From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).
Other outcomes:
Locations:
city: San Diego
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Minneapolis
country: United States
state: Minnesota
city: Cincinnati
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Edmonton
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
Study officials:
affiliation: Astellas Pharma US, Inc.
name: Central Contact
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.