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

Condition(s) targeted: Liver Transplantation

Intervention: tacrolimus modified release (MR) (Drug); tacrolimus (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Astellas Pharma Inc

Official(s) and/or principal investigator(s):
Central Contact, Study Director, Affiliation: Astellas Pharma US, Inc.

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.

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 design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome:

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

Minimum Observed Concentration of Tacrolimus (Cmin)

Patient Survival

Graft Survival

Secondary outcome:

Maximum Observed Concentration of Tacrolimus (Cmax)

Time to Maximum Observed Concentration of Tacrolimus (Tmax)

Percentage of Participants With Biopsy-confirmed Acute Rejection

Time to Event for Patient Non-survival

Time to Event for Graft Non-survival

Time to First Biopsy-confirmed Acute Rejection

Grade of Biopsy-confirmed Acute Rejection Episodes

Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection

Number of Participants With Multiple Rejection Episodes

Number of Participants With Clinically Treated Acute Rejection Episodes

Number of Participants With Chronic Rejection

Number of Participants With Treatment Failure

Primary Reason for Graft Loss

Change From Baseline in Alanine Aminotransferase (ALT)

Change From Baseline in Aspartate Aminotransferase (AST)

Change From Baseline in Total Bilirubin

Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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.

Palo Alto, California, United States

Denver, Colorado 80262, United States

Baltimore, Maryland 21287, United States

Ann Arbor, Michigan 48109, United States

Minneapolis, Minnesota 55455, United States

Rochester, Minnesota 55905, United States

New York, New York 10029, United States

Cincinnati, Ohio 45267, United States

Dallas, Texas 75246, United States

Madison, Wisconsin 53792, United States

Related publications:

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.

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.

Starting date: February 2003
Last updated: August 1, 2013