Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients

This study has been completed.
Sponsor:
Collaborator:
CTI Clinical Trial and Consulting Services
Information provided by (Responsible Party):
Veloxis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00496483
First received: July 2, 2007
Last updated: June 25, 2015
Last verified: June 2015

July 2, 2007
June 25, 2015
July 2007
March 2008   (final data collection date for primary outcome measure)
  • Evaluation of Steady State Tacrolimus Trough Levels (C24). [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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). [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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). [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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). [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, AUC was measured (0 to 24 hours).
Evaluation of steady state tacrolimus exposure (AUC 0-24) and trough levels (C24) in stable kidney transplant recipients converted from Prograf® (tacrolimus, Astellas Pharma US, Inc.) to LCP-Tacro in a three sequence study design. [ Time Frame: 22 days ]
Complete list of historical versions of study NCT00496483 on ClinicalTrials.gov Archive Site
  • Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 21. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 52 days ] [ Designated as safety issue: Yes ]
    A combination of deaths, graft failure and biopsy proven acute rejections (BPAR) was used to evaluate the safety.
  • To determine whether patients can be safely converted from Prograf to LCP-Tacro [ Time Frame: 52 days ]
  • To evaluate tacrolimus exposure and trough concentrations in stable kidney transplant recipients converted from Prograf to LCP-Tacro in a three-sequence study design [ Time Frame: 22 days ]
  • To determine the mean conversion ratio between Prograf twice-a-day and LCP Tacro once-a-day [ Time Frame: 22 days ]
  • To evaluate the safety of LCP-Tacro compared to Prograf [ Time Frame: 52 days ]
Not Provided
Not Provided
 
Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients
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
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.

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.

Interventional
Phase 2
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Renal Failure
  • Drug: LCP Tacro (tacrolimus)

    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.

    Other Name: tacrolimus
  • Drug: Prograf

    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.

    Other Name: Tacrolimus
Active Comparator: LCP-Tacro (tacrolimus)
Experimental: LCP Tacro; investigational product LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.
Interventions:
  • Drug: LCP Tacro (tacrolimus)
  • Drug: Prograf
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
March 2008
March 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00496483
LCP-Tacro 2011
No
Not Provided
Not Provided
Veloxis Pharmaceuticals
Veloxis Pharmaceuticals
CTI Clinical Trial and Consulting Services
Study Director: Alan Glicklich, MD Veloxis Pharmaceuticals
Veloxis Pharmaceuticals
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP