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

NCT00282243 | Completed Phase 2 Results

• 1 other identifier: 02-0-152
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 10

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.

Conditions

Liver Transplantation

Keywords

Pharmacokinetics; Therapy; Immunosuppression; Drugs, Investigational; Adult

Outcome Measures

Primary Outcomes (4)

• 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 the tacrolimus and tacrolimus MR treatment periods at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 for the morning (0-12 hour) and afternoon (12-24 hour) doses.

  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.

• Minimum Observed Concentration of Tacrolimus (Cmin)

  The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.

  Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for tacrolimus MR).

• Patient Survival

  Patient survival was defined as any participant known to be alive at 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 participant death.

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

Secondary Outcomes (17)

• Maximum Observed Concentration of Tacrolimus (Cmax)

  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.

• Time to Maximum Observed Concentration of Tacrolimus (Tmax)

  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.

• Percentage of Participants With Biopsy-confirmed Acute Rejection

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

Study Arms (1)

Tacrolimus MR

EXPERIMENTAL

After enrollment in the pharmacokinetic period, patients were maintained on their usual dose of tacrolimus twice daily on Day 1 through Day 14 and on Day 15 were converted to tacrolimus modified release (MR) once-daily in the morning for 14 days, converted back to tacrolimus twice daily for 14 days and then converted back to tacrolimus MR formulation once-daily in the morning for 14 days, all based on a 1:1 mg for mg total daily dose conversion. The extended treatment period began on day 57 and consisted of a single dose of tacrolimus extended-release formulation once every morning through the end of the study. Dose adjustments were allowed in order to maintain the target tacrolimus trough level within the range of 5 to 20 ng/mL and for clinical reasons.

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

Interventions

tacrolimus modified release (MR) DRUG

Oral

Also known as: Advagraf,, FK506E,, MR4,, FKMR,, Astagraf XL

Tacrolimus MR

tacrolimus DRUG

Oral

Also known as: Prograf,, FK506

Tacrolimus MR

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (10)

Unknown Facility

Palo Alto, California, United States

Location

Unknown Facility

Denver, Colorado, 80262, United States

Location

Unknown Facility

Baltimore, Maryland, 21287, United States

Location

Unknown Facility

Ann Arbor, Michigan, 48109, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55455, United States

Location

Unknown Facility

Rochester, Minnesota, 55905, United States

Location

Unknown Facility

New York, New York, 10029, United States

Location

Unknown Facility

Cincinnati, Ohio, 45267, United States

Location

Unknown Facility

Dallas, Texas, 75246, United States

Location

Unknown Facility

Madison, Wisconsin, 53792, United States

Location

Related Publications (2)

• 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.

  PMID: 17589349 BACKGROUND

• 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.

  PMID: 15848672 BACKGROUND

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

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 24, 2006
• First Posted: January 26, 2006
• Study Start: February 1, 2003
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: September 30, 2013
• Results First Posted: September 30, 2013

Record last verified: 2013-08

Locations

US (10)