Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients
Condition: Renal Transplant Rejection
Intervention: Prograf; Tacrolimus
Intervention description: Brand Drug for the duration of the study.; Generic
Intervention MeSH terms: Tacrolimus
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 176.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      As the patents for brand-name immunosuppressive medications expire, there is increasing
      interest in using generic immunosuppressive drugs. However, despite pharmacokinetic studies
      showing bioequivalence, questions remain regarding the clinical impact of use of generic
      immunosuppression.

      The most important immunosuppressive agent in the modern transplant era is arguably
      tacrolimus, a calcineurin-inhibitor with a narrow therapeutic index. This study seeks to
      answer the question regarding the clinical impact of generic tacrolimus use as measured
      primarily by acute rejection, loss of graft function, and patient death through a randomized
      trial of 2 phases: Brand tacrolimus only, and Generic A tacrolimus only. Given that kidney
      transplantations are the most commonly performed transplants with well-defined measures of
      rejection and graft failure, this organs will be studied in a six-center study designed to
      accrue the target number of transplant recipients within the one-year study period.

      The study has now been branched off into 2 phases. Phase 1: consists of randomization of
      patients onto brand and generic tacrolimus. This was completed once 40 brand patients were
      enrolled. Phase 2: consists of patients being enrolled only on generic tacrolimus (standard
      of care from subject's insurance). This will be completed once there is a total of 160
      generic participants. 200 participants total in the study.
    

Eligibility criteria:

        Inclusion Criteria

          1. Signed informed consent and or/assent

          2. Between the ages of 18 and 70 years, inclusive

          3. Current or future kidney transplant recipients, no more than 14 days after transplant
             and prior to hospital discharge. Inclusion of future kidney transplant recipients
             cannot exceed 30-days pre-transplant.

          4. Able to swallow tablets and capsules at the time of randomization

          5. Subjects must be receiving a primary or secondary kidney allograft from a deceased
             donor or from a non- HLA identical living donor

          6. Negative cross match test, and compatible (A, B, AB or O) blood type

          7. Subjects must have no known contraindications to tacrolimus

          8. Women of childbearing potential (WOCBP) must have a negative pregnancy test and be
             willing to use 2 methods of contraception during the study and for 6 weeks after
             stopping the study drug.

        WOCBP includes any female who has experienced menarche and who has not undergone successful
        surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
        or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on
        hormone replacement therapy with documented serum follicle stimulating hormone level > 35
        mIU/cc). Women who are using oral, implanted, or injectable contraceptive hormones
        (intrauterine device), mechanical products or barrier methods (diaphragm, condoms,
        spermicides), are practicing abstinence, or have a sterile partner (e.g., vasectomy), will
        be considered of child bearing potential.

        In addition, WOCBP who are taking MMF must use methods of birth control as stipulated in
        the package insert, namely:

        Either intrauterine device, or partner with vasectomy, or one hormone (oral contraceptive
        pill, transdermal patch, vaginal ring, or progesterone injection or implant) and one
        barrier method (diaphragm or cervical cap with spermicide, contraceptive sponge, or male or
        female condom), or two barrier methods as described above.

        WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent
        units of human chorionic gonadotropin [HCG]) at the time of transplant.

        Exclusion Criteria

          1. Those who receive simultaneous combined organ transplants

          2. Subjects with clinically significant active infections (for example, those requiring
             hospitalization, or as judged by the Investigator) or malignancies

          3. Recipients who are concurrently receiving belatacept or anticipate to receive
             belatacept as part of their immunosuppressive regimen

          4. Subjects currently enrolled in another investigational device or drug study

          5. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
             the entire study period and for 6 weeks after stopping the study drug

          6. Women who are breast-feeding or pregnant with a positive pregnancy test on enrollment
             or prior to study drug administration

          7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious disease) illness must
             not be enrolled into this study.

          8. Any psychiatric or medical condition that, in the investigator's opinion, may put the
             subject at significant risk, may confound the study results, or may interfere
             significantly with the subject's participation in the study.