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Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients

Primary Purpose

Renal Failure

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LCP Tacro (tacrolimus)
Prograf
Sponsored by
Veloxis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Failure focused on measuring Tacrolimus, Pharmacokinetics, Kidney Transplantation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men and women 18-65 years of age who are recipients of a renal transplant at least 6 months prior to enrollment
  • Patients on oral Prograf therapy as part of their maintenance immunosuppression therapy, with stable doses and trough levels of tacrolimus of 7-12 ng/mL for at least two weeks prior to enrollment.
  • Patients maintained on concurrent immunosuppression with mycophenolate mofetil (MMF, CellCept) or mycophenolic acid delayed-release tablets (Myfortic), with stable doses for at least two weeks prior to enrollment
  • Patients with serum creatinine < 2.0mg/dL prior to enrollment
  • Able to swallow study medication
  • Patients capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study
  • Women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication
  • Patients who successfully pass a drug screen

Exclusion Criteria:

  • Recipients of any transplanted organ other than a kidney
  • White blood cell count < 2.8 x 10^9 /L
  • Patients who are receiving a total dose of Prograf for 24 hours < 3mg
  • Patients unable or unwilling to provide informed consent
  • Pregnant or nursing women
  • Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception
  • Administration of other investigational agent in the three months prior to enrollment
  • Patient receiving any drug interfering with tacrolimus metabolism
  • Patients who have taken sirolimus within the past three months prior to screening
  • Patient with an episode of acute cellular requiring antibody therapy within the 6 months prior to enrollment
  • Patient treated for acute cellular rejection within the 30 days prior to enrollment
  • Patient who is HCV negative and has received an HCV positive (HCV RNA by PCR or HCV antibody) donor kidney
  • Patient has a current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully
  • Patient has uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives
  • Patient has severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of tacrolimus
  • Patient will require therapy with any immunosuppressive agent other than those prescribed in the study
  • Patient has a known hypersensitivity to corticosteroids, mycophenolate mofetil, mycophenolic acid or tacrolimus
  • Patient has any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator

Sites / Locations

  • University of Cincinnati
  • Methodist Hospital Houston

Arms of the Study

Arm 1

Arm Type

Active Comparator

Arm Label

LCP-Tacro (tacrolimus)

Arm Description

Experimental: LCP Tacro; investigational product LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.

Outcomes

Primary Outcome Measures

Evaluation of Steady State Tacrolimus Trough Levels (C24).
Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).
Patients had a baseline AUC measured (0 to 24 hours) at day 7 before conversion to LCP-Tacro.
Evaluation of Steady State Tacrolimus Exposure Trough Levels (C24).
Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, a trough level (C24) was measured.
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).
Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, AUC was measured (0 to 24 hours).

Secondary Outcome Measures

Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 21.
Cmax and Cavg was measured at day 21 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 21.
Tmax was measured at day 21 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 21.
Degree og fluctuation and degree of swing was measured at day 21 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 7.
Cmax and Cavg was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 7.
Tmax was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 7.
Degree og fluctuation and degree of swing was measured as baseline at day 7 (Cmin was measured as part of the primary outcome).
Safety Evaluation
A combination of deaths, graft failure and biopsy proven acute rejections (BPAR) was used to evaluate the safety.

Full Information

First Posted
July 2, 2007
Last Updated
June 25, 2015
Sponsor
Veloxis Pharmaceuticals
Collaborators
CTI Clinical Trial and Consulting Services
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1. Study Identification

Unique Protocol Identification Number
NCT00496483
Brief Title
Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients
Official Title
A Phase II, Open-Label, Multi-Center Prospective, Conversion Study in Stable Kidney Transplant Patients to Compare the Pharmacokinetics of LCP-Tacro Tablets Once-A-Day to Prograf® Capsules Twice-A-Day
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Veloxis Pharmaceuticals
Collaborators
CTI Clinical Trial and Consulting Services

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
A three sequence, open-label, multi-center, prospective, study in stable kidney transplant patients to assess and compare the pharmacokinetics (Cmax, C24, and AUC), and safety of LCP-Tacro (tacrolimus) tablets versus Prograf (tacrolimus) capsules.
Detailed Description
A three sequence, open-label, multi-center, prospective, study in stable kidney transplant patients to assess and compare the pharmacokinetics (Cmax, C24, and AUC), and safety of LCP-Tacro (tacrolimus) tablets versus Prograf (tacrolimus) capsules. Stable kidney transplant patients who fulfill all I/E criteria will be enrolled and kept on Prograf for 7 days. Following a 24-hour PK study on Day 7 to determine pharmacokinetics for Prograf, all patients will be converted to once daily LCP-Tacro for 7 days with no dose changes allowed. On Day 14 and Day 21 a 24-hour LCP-Tacro PK study will be performed. On Day 22 patients will be converted back to their original twice daily dose of Prograf for a safety follow-up period of 30 days ending with a safety assessment on day 53.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Failure
Keywords
Tacrolimus, Pharmacokinetics, Kidney Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LCP-Tacro (tacrolimus)
Arm Type
Active Comparator
Arm Description
Experimental: LCP Tacro; investigational product LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.
Intervention Type
Drug
Intervention Name(s)
LCP Tacro (tacrolimus)
Other Intervention Name(s)
tacrolimus
Intervention Description
Prograf will be administrated twice a day, per product labeling, with an interval of 12 ± 1 hours between the morning and evening doses. Patients will continue on the same dose on Day0 through Day 7 to maintain target trough levels of 7-12 ng/mL. On the morning of Day 8, following the final blood draw for the PK assessment, patient will be converted to LCP-Tacro using the conversion Ratio 0.66-0.8. LCP-Tacro tablets will be administered orally once daily in the morning, with an interval of 24 ± 1 hours between doses. Other Names: Tacrolimus modified-release LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.
Intervention Type
Drug
Intervention Name(s)
Prograf
Other Intervention Name(s)
Tacrolimus
Intervention Description
Prograf will be administrated twice a day, per product labeling, with an interval of 12 ± 1 hours between the morning and evening doses. Patients will continue on the same dose on Day0 through Day 7 to maintain target trough levels of 7-12 ng/mL. On the morning of Day 8, following the final blood draw for the PK assessment, patient will be converted to LCP-Tacro using the conversion Ratio 0.66-0.8. LCP-Tacro tablets will be administered orally once daily in the morning, with an interval of 24 ± 1 hours between doses. Other Names: Tacrolimus modified-release LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.
Primary Outcome Measure Information:
Title
Evaluation of Steady State Tacrolimus Trough Levels (C24).
Description
Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.
Time Frame
7 days
Title
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).
Description
Patients had a baseline AUC measured (0 to 24 hours) at day 7 before conversion to LCP-Tacro.
Time Frame
7 days
Title
Evaluation of Steady State Tacrolimus Exposure Trough Levels (C24).
Description
Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, a trough level (C24) was measured.
Time Frame
21 days
Title
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).
Description
Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, AUC was measured (0 to 24 hours).
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 21.
Description
Cmax and Cavg was measured at day 21 (Cmin was measured as part of the primary outcome).
Time Frame
21 days
Title
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 21.
Description
Tmax was measured at day 21 (Cmin was measured as part of the primary outcome).
Time Frame
21 days
Title
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 21.
Description
Degree og fluctuation and degree of swing was measured at day 21 (Cmin was measured as part of the primary outcome).
Time Frame
21 days
Title
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 7.
Description
Cmax and Cavg was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Time Frame
7 days
Title
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 7.
Description
Tmax was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Time Frame
7 days
Title
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 7.
Description
Degree og fluctuation and degree of swing was measured as baseline at day 7 (Cmin was measured as part of the primary outcome).
Time Frame
7 days
Title
Safety Evaluation
Description
A combination of deaths, graft failure and biopsy proven acute rejections (BPAR) was used to evaluate the safety.
Time Frame
52 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women 18-65 years of age who are recipients of a renal transplant at least 6 months prior to enrollment Patients on oral Prograf therapy as part of their maintenance immunosuppression therapy, with stable doses and trough levels of tacrolimus of 7-12 ng/mL for at least two weeks prior to enrollment. Patients maintained on concurrent immunosuppression with mycophenolate mofetil (MMF, CellCept) or mycophenolic acid delayed-release tablets (Myfortic), with stable doses for at least two weeks prior to enrollment Patients with serum creatinine < 2.0mg/dL prior to enrollment Able to swallow study medication Patients capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study Women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication Patients who successfully pass a drug screen Exclusion Criteria: Recipients of any transplanted organ other than a kidney White blood cell count < 2.8 x 10^9 /L Patients who are receiving a total dose of Prograf for 24 hours < 3mg Patients unable or unwilling to provide informed consent Pregnant or nursing women Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception Administration of other investigational agent in the three months prior to enrollment Patient receiving any drug interfering with tacrolimus metabolism Patients who have taken sirolimus within the past three months prior to screening Patient with an episode of acute cellular requiring antibody therapy within the 6 months prior to enrollment Patient treated for acute cellular rejection within the 30 days prior to enrollment Patient who is HCV negative and has received an HCV positive (HCV RNA by PCR or HCV antibody) donor kidney Patient has a current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully Patient has uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives Patient has severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of tacrolimus Patient will require therapy with any immunosuppressive agent other than those prescribed in the study Patient has a known hypersensitivity to corticosteroids, mycophenolate mofetil, mycophenolic acid or tacrolimus Patient has any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Glicklich, MD
Organizational Affiliation
Veloxis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Methodist Hospital Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients

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