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

Study Overview
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Brief Summary
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This study will investigate whether converting patients from FDA approved immediate-release tacrolimus to FDA approved extended release tacrolimus (Envarsus) reduces neurological side-effects, improves quality of life, and enhances adherence. A select group of elderly (> 60 years of age) patients, who are especially sensitive to tacrolimus-related adverse (AEs) effects, will be provided the opportunity to convert to Envarsus with this study.

Detailed Description
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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.

Official Title
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An Evaluation of Converting Elderly Kidney Transplant Recipients From Tacrolimus to Envarsus to Limit Neurological Adverse Events and Improve Quality of Life

Conditions
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Disorder Related to Renal Transplantation

Intervention / Treatment
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* Drug: Tacrolimus XR (Envarsus)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is a recipient of a living donor or deceased donor kidney only transplant Subject is > 60 years of age Subject reports neurological AEs from tacrolimus that include one or more of the following: insomnia, vertigo, photophobia, mood disturbances, tremor, and/or headache. Patients must be able to understand English and provide written informed consent 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 Patients with a screening tacrolimus trough level of 3-12 ng/mL, measured between Day -7 to 0 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) Patients must be willing to commit to and comply with the schedule of study visits Exclusion Criteria: Multi-organ transplant Subjects not taking tacrolimus post-transplant Documented Parkinson's disease or dementia Known cause of neurological symptoms other than tacrolimus Patients with significant visual and hearing impairments affecting their ability to complete the study requirements and assessments Patients with any severe medical condition (including infection) requiring acute or chronic treatment that in the Investigator's opinion would interfere with study participation 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 Patients who are taking any acute or chronic medications that may impact reaction time, memory, or sleep habits, based on Investigator discretion Patients with any form of current drug or alcohol abuse as assessed by the Investigator

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tacrolimus XR<br> | Drug: Tacrolimus XR (Envarsus)<br>* Elderly patients (age 60 or older) on tacrolimus experiencing neurological AEs (tremor, insomnia, vertigo, photophobia, mood disturbances, or headache) presumably from tacrolimus immediate-release or tacrolimus XL will be converted to Envarsus. This conversion will be based on the Envarsus package insert which is a 20% reduction in total daily dose and is taken once a day. The conversion from Astagraf to Envarsus will be a 36% reduction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (QOL) | Mean change in QOL scores from baseline to day 14 and day 28 after conversion from tacrolimus to Envarsus. | through study completion, an average of two years | 
| Neurological Scores | Mean change in neurological scores (including insomnia, vertigo, photophobia, mood, headache, and tremor) from baseline to day 14 and day 28 after conversion from tacrolimus to Envarsus. | through study completion, an average of two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tacrolimus preference | Proportion of patients preferring Envarsus compared with their previous tacrolimus formulation after 28 days of treatment | through study completion, an average of two years | 
| Non-adherence | Percent of patients reporting non-adherence from baseline to day 14 and 28 after conversion from tacrolimus to Envarsus. | through study completion, an average of two years | 
| Incremental costs | Mean incremental costs from baseline to day 28 following conversion to Envarsus. | through study completion, an average of two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplant, immunosuppression, tacrolimus XR, elderly, quality of life, neurological adverse events