Converting Elderly Kidney Transplant Recipients From Tacrolimus to Envarsus to Limit Neurological AE and Improve QOL

Tacrolimus (Prograf) is a calcineurin inhibitor that is widely used in all types of solid
organ transplants. However, one of the major limitations in using tacrolimus are the adverse
effects that significantly reduce a transplant recipient's quality-of-life (QOL). These QOL
reducing AEs associated with tacrolimus include post-transplant diabetes mellitus,
neurotoxicity, diarrhea, nephrotoxicity, and alopecia. A recent open-label, multicenter,
prospective phase 3b study showed that Envarsus significantly reduced tremors and improved
quality of life when compared to tacrolimus. It is postulated that the mechanism behind
tremor reduction occurs as a result of lower Cmax tacrolimus concentrations with the new
Envarsus formulation. Given its ability for tremor improvement, it would be beneficial to
investigate whether conversion from tacrolimus to Envarsus can improve other neurological AEs
such as insomnia vertigo, photophobia, mood disturbances, or headache. In particular, the
elderly are especially sensitive to tacrolimus-related AEs and may benefit from tacrolimus to
Envarsus conversion. Further, it is useful to understand the cost effectiveness of converting
to Envarsus in this patient population.

Study duration: 35 days per subject until a total of 40 subjects are enrolled. Patients will
have a total of 4 visits.

Inclusion Criteria:

1. The subject is a recipient of a living donor or deceased donor kidney only transplant

2. Subject is > 60 years of age

3. Subject reports neurological AEs from tacrolimus that include one or more of the
following: insomnia, vertigo, photophobia, mood disturbances, tremor, and/or headache.

4. Patients must be able to understand English and provide written informed consent

5. Patients receiving a stable dose (i.e., no dose adjustments) of immediate-release
tacrolimus (Prograf) or extended-release tacrolimus (Astagraf) for a minimum of 4-7
days at screening

6. Patients with a screening tacrolimus trough level of 3-12 ng/mL, measured between Day
-7 to 0

7. The patient is not scheduled to begin any new medication that could interfere with
tacrolimus blood levels, including prescription and over-the-counter medications,
herbal or food supplements (including grapefruit and pomegranate products)

8. Patients must be willing to commit to and comply with the schedule of study visits

Exclusion Criteria:

1. Multi-organ transplant

2. Subjects not taking tacrolimus post-transplant

3. Documented Parkinson's disease or dementia

4. Known cause of neurological symptoms other than tacrolimus

5. Patients with significant visual and hearing impairments affecting their ability to
complete the study requirements and assessments

6. Patients with any severe medical condition (including infection) requiring acute or
chronic treatment that in the Investigator's opinion would interfere with study
participation

7. Known non-adherence (defined as documentation in the patient chart of multiple missed
visits and/or medication doses) which in the investigator's opinion would interfere
with the objectives of the study

8. Patients who are taking any acute or chronic medications that may impact reaction
time, memory, or sleep habits, based on Investigator discretion

9. Patients with any form of current drug or alcohol abuse as assessed by the
Investigator