Clinical trial NCT00282243: A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Liver Transplant Patients
Official title: A Phase 2, Open-Label, Multi-Center Study to Assess the Pharmacokinetics, Long-term Safety and Tolerability of Tacrolimus in Stable Liver 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: Liver Transplantation
Keywords: Pharmacokinetics
Therapy
Immunosuppression
Drugs, Investigational
Adult
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2006-01-26
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 liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.

Detailed description: A one arm study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (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 liver 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 liver
* 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: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
measure: Minimum Observed Concentration of Tacrolimus (Cmin)
timeFrame: Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for tacrolimus MR).
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: Maximum Observed Concentration of Tacrolimus (Cmax)
timeFrame: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
measure: Time to Maximum Observed Concentration of Tacrolimus (Tmax)
timeFrame: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
measure: Percentage of Participants With Biopsy-confirmed Acute Rejection
timeFrame: From enrollment until the end of study (up to 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: Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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 Aspartate Aminotransferase (AST)
timeFrame: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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 Total Bilirubin
timeFrame: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 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 last dose day plus 10 days (approximately 60 months).
Other outcomes:
Locations:
city: Palo Alto
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Baltimore
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Dallas
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Astellas Pharma US, Inc.
name: Central Contact
role: STUDY_DIRECTOR
References:
citation: Florman S, Alloway R, Kalayoglu M, Punch J, Bak T, Melancon J, Klintmalm G, Busque S, Charlton M, Lake J, Dhadda S, Wisemandle K, Wirth M, Fitzsimmons W, Holman J, First MR. Once-daily tacrolimus extended release formulation: experience at 2 years postconversion from a Prograf-based regimen in stable liver transplant recipients. Transplantation. 2007 Jun 27;83(12):1639-42. doi: 10.1097/01.tp.0000265445.09987.f1.
citation: Florman S, Alloway R, Kalayoglu M, Lake K, Bak T, Klein A, Klintmalm G, Busque S, Brandenhagen D, Lake J, Wisemandle K, Fitzsimmons W, First MR. Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen. Transplant Proc. 2005 Mar;37(2):1211-3. doi: 10.1016/j.transproceed.2004.11.086.