Pharmacokinetics of LCP-Tacro in Stable Liver Transplant Patients
Condition: Liver Failure
MeSH terms: Liver Failure
Intervention: LCP Tacro; Prograf
Intervention description: In the morning of Day 8 (after completing one week treatment with Prograf), all patients will be converted to LCP Tacro QD with a conversion ratio of 0.66-0.8.
LCP-Tacro will be administered for 14 Days with one fixed dose change allowed at Day 15. LCP-Tacro will be administered orally once daily in the morning, with an interval of 24 ± 1 h between doses.
Trough levels were to be maintained within predefined therapeutic ranges of 5 to 15 ng/mL.; 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 Day 0 through Day 7 to maintain target trough levels of 5-12 ng/mL.
Intervention MeSH terms: Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Tacrolimus; Pharmacokinetics; Liver Transplantation

Summary:

      A three sequence, open-label, multi-center, prospective, study in stable liver transplant
      patients to assess and compare the pharmacokinetics (Cmax, C24, and AUC), and safety of
      LCP-Tacro (tacrolimus) tablets versus Prograf (tacrolimus) capsules.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women 18-65 years of age who are recipients of a liver transplant at least six
             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 5-12 ng/mL for at least
             four weeks prior to enrollment with at least two measurements at least two days apart
             in the screening period up to fourteen days prior to enrollment

          -  Concurrent immunosuppression with mycophenolate mofetil (MMF, CellCept) or
             mycophenolic acid delayed-release tablets (Myfortic) is allowed but patients on either
             of these medications should be on stable doses for at least four weeks prior to
             enrollment

          -  Patients with stable serum bilirubin, AST, ALT, and Alk Phos or GGT that are ≤ 2 times
             the upper limit of normal based on local laboratory criteria

          -  Patients with serum creatinine ≤2.0 mg/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 protocol.

          -  Women of childbearing potential must have a negative serum pregnancy test within seven
             days prior to receiving study medication and agree to use contraceptive measures to
             avoid pregnancy during participation in the trial.

        Exclusion Criteria:

          -  Recipients of any transplanted organ other than a liver

          -  White blood cell count ≤ 2.8 x 109/L

          -  Patients who are receiving a total dose of Prograf < 3 mg per 24 hours

          -  Patients who are receiving more than 10 mg of prednisone per day

          -  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 any other investigational agent in the three months prior to
             enrollment

          -  Patients receiving any drug interfering with tacrolimus metabolism

          -  Patients who have taken sirolimus within the three months prior to screening

          -  Patient with an episode of acute cellular requiring antibody therapy within the six
             months prior to enrollment

          -  Patients treated for acute cellular rejection within the thirty days prior to
             enrollment

          -  Patient who is HCV negative and has received an HCV positive (HCV RNA by PCR or HCV
             antibody) donor liver

          -  Patients presenting after liver transplantation with recurrent HCV infection,
             documented by presence of HCV RNA in serum and grade II or greater inflammation or
             stage II or greater fibrosis on liver biopsy

          -  Patients being actively treated with antiviral therapy, such as interferons or
             ribavirin, for recurrent hepatitis C.

          -  Patients with an alpha-feto protein ≥ 20 ng/mL

          -  Patient has a current malignancy or a history of malignancy (within the past five
             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 or tacrolimus

          -  Patient has any form of current substance abuse (patients must pass a standard drug
             screen), psychiatric disorder or a condition that, in the opinion of the Investigator,
             may invalidate communication with the Investigator Version