Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients

Patients will be identified when an organ from live or deceased donor becomes available for
kidney transplant. Prior to receiving their kidney transplant, subjects will be screened for
inclusion/exclusion criteria on the day of transplantation. During the pre-operative
preparation for transplant, patients will be consented for surgery and consented for the
study at the same time if they volunteer to be included. The transplant surgeon performing
the transplant operation will be responsible for screening the patients for inclusion and
exclusion criteria as well as obtaining informed consent. Patients will need to provide
informed consent to be included in the study, and will receive a copy of their consent. Each
potential participant will be approached by the transplant surgeon and informed of all
information pertinent to the study prior to providing consent. No advertisements for
recruitment will be performed and no compensation will be provided for participation.

This study is a single center prospective observational study conducted at Temple University
Hospital (TUH). All participants will be consented for all procedures involved in this study.
This study will utilize the QUEST questionnaire (attached) to evaluate the severity of
tremors at 1 month. Data to be collected includes tacrolimus trough levels, study drug
dosing, hemoglobin A1c, incidence and severity of tremors, potassium, glomerular filtration
rate, and rejection episodes.

Day 0 Study drug (tacrolimus) initiated at 0.13/mg/kg/day for all patients (the day of
initiation decided per transplant surgeon discretion)

Day 0-4 Inpatient laboratory parameters checked every 24 hours (serum creatinine, tacrolimus
level, glomerular filtration rate, potassium, blood glucose)

Day 4-30 Outpatient laboratory parameters checked three times weekly on Monday, Wednesday,
and Friday (serum creatinine, tacrolimus level, glomerular filtration rate, potassium, blood
glucose)

Day 30 visit (within 5 days) Draw tacrolimus trough levels, serum creatinine, estimated
glomerular filtration rate, serum potassium, and blood glucose. Complete tremor questionnaire
with participant.

During or prior to Day 30 visit Oral swab performed to be analyzed for testing of metabolic
enzymatic activity (This will be performed to determine ability of the patient to metabolize
tacrolimus)

Inclusion Criteria:

Adult patient who is 18 years of age or older receiving a kidney transplant at the Temple
University Hospital's Kidney Transplant Program who are capable of understanding consent
and volunteer to take part in the study

Exclusion Criteria:

Scheduled for multiple organ transplant at enrollment Non-English speaking Pregnant women
Moderate-severe hepatic impairment (Child Pugh > 10 or bilirubin > 2) Existing
contraindications to tacrolimus-based products including known hypersensitivity to
tacrolimus or any other component of the formulation Receiving concomitant medications
known to have strong drug-drug interaction potential with tacrolimus including fluconazole,
voriconazole, posaconazole, isavuconazole, itraconazole, ketoconazole, diltiazem,
verapamil, metronidazole, erythromycin, clarithromycin, rifampin, rifabutin, rifapentine,
phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, St. John's Wort,
efavirenz, neivrapine, etravirine, atazanavir, darunavir, fosamprenavir, indinavir,
lopinavir, ritonavir, nelfinavir, saquinavir, tipranavir, cobicistat