Pharmacokinetics of LCP-Tacro™ Once Daily and Prograf® Twice A Day in Adult De Novo Liver Transplant Patients
Condition: Liver Failure
MeSH terms: Liver Failure
Intervention: LCP -Tacro; Prograf
Intervention description: LCP-Tacro tablets will be administered orally once daily in the morning starting at 0.07 - 0.11 mg/kg. The starting dose for African-American patients will be 0.09 - 0.13 mg/kg. Subsequent doses of each study drug will be adjusted to maintain target whole blood tacrolimus trough levels of 5 - 20 ng/mL.
Other Names:Tacrolimus modified-release LCP-Tacro™ tablets (0.5 mg, 1 mg, 2 mg, 5 mg); Oral Prograf capsules will be administered starting at 0.10 - 0.15 mg/kg per day in two equally divided morning and evening doses. Subsequent doses of each study drug will be adjusted to maintain target whole blood tacrolimus trough levels of 5 - 20 ng/mL.
Other name: tacrolimus Prograf® capsules (0.5 mg, 1 mg, 5 mg)
Intervention MeSH terms: Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver; Hepatic; Transplantation; Immunosuppression; Tacrolimus; Prograf

Summary:

      The purpose of this study is to demonstrate the pharmacokinetics (PK, measuring the amount of
      medication in blood samples) and safety of a new medicine, LCP-Tacro™ tablets, and Prograf®
      capsules, a drug commonly taken by transplant recipients to prevent the body from rejecting a
      transplanted kidney and liver. LCP-Tacro is a tablet containing the same active ingredient
      (tacrolimus) that is in Prograf capsules, but the tablet has been designed to release
      tacrolimus over an extended period so that it only has to be taken once daily. LCP-Tacro is
      an investigational drug.

      This study will evaluate the levels of tacrolimus in the blood in the first two weeks after a
      liver transplant in patients randomly assigned (by chance, like flipping a coin) to take
      either LCP-Tacro™ tablets (tacrolimus) once daily or Prograf® capsules twice daily. In
      addition, patients will remain on study drug for 360 days in order to evaluate the relative
      safety of LCP-Tacro™ tablets compared to Prograf over a longer period of time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult men and women at least 18 years of age who are recipients of a liver transplant
             from a deceased donor with a Model for End-Stage Liver Disease (MELD) score at the
             time of transplantation of ≤ 30 who are able to give informed consent for
             participation

        Exclusion Criteria:

          -  Recipient of any transplanted organ other than a liver

          -  Recipients of a liver from a non-heart beating donor

          -  Recipients of a liver from an ABO incompatible donor

          -  Recipients of a bone marrow or stem cell transplant

          -  Patients with a white blood cell count ≤ 2.8 x 109/L unless the absolute neutrophil
             count (ANC) is > 1.0 x 109/L

          -  Patients who fail a drugs of abuse screen in the pre-transplant evaluation

          -  Patients unable to swallow study medication

          -  Patients incapable of understanding the purposes and risks of the study, who cannot
             give written informed consent, or who are unwilling to comply with the study protocol

          -  Pregnant or nursing women (women of childbearing potential must have a negative serum
             pregnancy test within seven days prior to receiving study medication)

          -  Patients with reproductive potential who are unwilling/unable to use a double barrier
             method of contraception throughout the duration of the study

          -  Patients who were treated with any other investigational agent in the 30 days prior to
             enrollment

          -  Patients seropositive for human immunodeficiency virus (HIV)

          -  Patients with 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, or hepatocellular carcinoma (HCC) that meet the Milan
             Criteria for liver transplantation

          -  Patients with uncontrolled concomitant infection, a systemic infection requiring
             treatment, or any other unstable medical condition that could interfere with the study
             objectives

          -  Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal
             disorder that may affect the absorption of tacrolimus

          -  Patients with a known hypersensitivity to tacrolimus

          -  Patients with any form of current substance abuse, psychiatric disorder or a condition
             that, in the opinion of the Investigator, may invalidate communication with the
             Investigator

        Randomization to one of two treatment groups will be done post transplantation provided
        that the patient fulfills the following additional criteria:

          -  Patient is able to receive their first dose of randomized study drug orally within 72
             hours after the transplant surgery (graft reperfusion)

          -  Patient was NOT given intravenous tacrolimus prior to their first oral dose of study
             medication

          -  Recipient of a liver with a cold ischemia time of ≤ 10 hours