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

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

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.

Study Overview

• Status: Completed
• Conditions: Disorder Related to Renal Transplantation
• Intervention / Treatment: Drug: Tacrolimus XR (Envarsus)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll elderly kidney transplant recipients who are at least 60 years of age and have experienced neurological adverse events while on generic tacrolimus, Prograf, or Astagraf XL.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Crossover
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Tacrolimus XR

Drug: Tacrolimus XR (Envarsus); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Veloxis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: August 25, 2017
• First Posted (Actual): August 28, 2017

Study Record Updates

• Last Update Posted (Actual): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: quality of life; immunosuppression; elderly; kidney transplant; tacrolimus XR; neurological adverse events
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 2017-0400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No