Safety, Tolerability and Pharmacokinetics of Oral CellCept (Mycophenolate Mofetil) in Pediatric Liver Transplant Recipients on Concomitant Treatment With Cyclosporine and Corticosteroids
Condition: Pediatric Liver Transplantation
Intervention: Corticosteroids; Cyclosporine; mycophenolate mofetil
Intervention description: Corticosteroids will be administered as per center practice. The choice of corticosteroid drug will also be based on center practice.; Cyclosporine will be administered as per center practice.; Part 1: Mycophenolate mofetil will be administered as per center practice. Part 2: Mycophenolate mofetil will be administered as per dose determined in Part 1.
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 3 Months
Maximum age: 12 Years
Healthy volunteers: No

Summary:

      The study is planned to be conducted in 2 parts. The first part (open label, multi-center,
      non-controlled) of the study will estimate a dose that would provide a mycophenolic acid
      (MPA) exposure in pediatric participant that is comparable to that achieved in adult liver
      transplant participants receiving the approved dose of mycophenolate mofetil (MMF, CellCept).
      The second part (open-label, multi-center, single-arm Phase IV study) of the study will
      provide the pharmacokinetics, efficacy and safety profile of the proposed dose in the
      immediate post-transplant period. This study will be conducted at two centers based in the
      United States of America. Twelve pediatric transplant participants receiving a first liver
      allograft from a cadaveric or living donor will be enrolled in this study. Stable pediatric
      liver transplant participants who are at least 6 months post-transplant and who were already
      receiving stable dose of MMF in combination with cyclosporine will be enrolled into the
      study. Participants should have received stable MMF dose according to center practice for at
      least seven days in order to get steady state pharmacokinetics (PK). Participants also should
      have received stable concomitant doses of cyclosporine (for at least 2 days) and
      corticosteroids per center practice. Participants will be aged between 9 months and 12 years,
      with at least 6 participants greater than or equal to (>/=) 9 months and less than (<) 36
      months, of whom at least 2 will be <24 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participant must be between 3 months and 12 years of age

          -  Participant is a recipient of a first liver allograft from cadaveric or living donors

          -  Participant is a single-organ recipient (liver only)

          -  Female participants of childbearing potential must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 milli International Units per
             milliliter (mIU/mL) within one week prior to PK sampling

          -  Female participants of childbearing potential must use two reliable forms of
             contraception simultaneously unless abstinence is the chosen method

          -  Effective contraception must be used before beginning of PK sampling

          -  Participants must be able to receive oral medication

          -  Participants must be at least 6 months post-transplant and had started on MMF in the
             early post-transplant period (within 2 weeks of transplant)

          -  Participants must be receiving stable doses of MMF per center practice for at least 7
             days prior to PK sampling

          -  In addition, participants must be receiving stable doses of cyclosporine and
             corticosteroids, according to center practice

          -  Participants' parent/guardian are capable of understanding the purposes and risks of
             the study and must sign an informed consent for the study

        Exclusion Criteria:

          -  Pregnant or nursing adolescents

          -  Participants who had undergone dialysis within two weeks before PK sampling

          -  Participants with active systemic infections

          -  Participants with absolute neutrophil counts (ANC) of less than 1300 per microliter
             (µL), or platelets counts less than 50 000/µL or hemoglobin at a concentration below a
             set lower limit (according to center practice, but not less than 8 grams per
             deciliter) at the time of study entry

          -  Participants with active peptic ulcer disease

          -  Participants with severe diarrhea (more than 5 watery stools per day) or other
             gastrointestinal disorders which might interfere with their ability to absorb oral
             medication

          -  History of positive human immunodeficiency virus (HIV) test