<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03263052</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0400</org_study_id>
    <nct_id>NCT03263052</nct_id>
  </id_info>
  <brief_title>Converting Elderly Kidney Transplant Recipients From Tacrolimus to Envarsus to Limit Neurological AE and Improve QOL</brief_title>
  <official_title>An Evaluation of Converting Elderly Kidney Transplant Recipients From Tacrolimus to Envarsus to Limit Neurological Adverse Events and Improve Quality of Life</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Illinois at Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Veloxis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Illinois at Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate whether converting patients from FDA approved immediate-release&#xD;
      tacrolimus to FDA approved extended release tacrolimus (Envarsus) reduces neurological&#xD;
      side-effects, improves quality of life, and enhances adherence. A select group of elderly (&gt;&#xD;
      60 years of age) patients, who are especially sensitive to tacrolimus-related adverse (AEs)&#xD;
      effects, will be provided the opportunity to convert to Envarsus with this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tacrolimus (Prograf) is a calcineurin inhibitor that is widely used in all types of solid&#xD;
      organ transplants. However, one of the major limitations in using tacrolimus are the adverse&#xD;
      effects that significantly reduce a transplant recipient's quality-of-life (QOL). These QOL&#xD;
      reducing AEs associated with tacrolimus include post-transplant diabetes mellitus,&#xD;
      neurotoxicity, diarrhea, nephrotoxicity, and alopecia. A recent open-label, multicenter,&#xD;
      prospective phase 3b study showed that Envarsus significantly reduced tremors and improved&#xD;
      quality of life when compared to tacrolimus. It is postulated that the mechanism behind&#xD;
      tremor reduction occurs as a result of lower Cmax tacrolimus concentrations with the new&#xD;
      Envarsus formulation. Given its ability for tremor improvement, it would be beneficial to&#xD;
      investigate whether conversion from tacrolimus to Envarsus can improve other neurological AEs&#xD;
      such as insomnia vertigo, photophobia, mood disturbances, or headache. In particular, the&#xD;
      elderly are especially sensitive to tacrolimus-related AEs and may benefit from tacrolimus to&#xD;
      Envarsus conversion. Further, it is useful to understand the cost effectiveness of converting&#xD;
      to Envarsus in this patient population.&#xD;
&#xD;
      Study duration: 35 days per subject until a total of 40 subjects are enrolled. Patients will&#xD;
      have a total of 4 visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">January 1, 2020</completion_date>
  <primary_completion_date type="Actual">January 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Crossover</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Quality of life (QOL)</measure>
    <time_frame>through study completion, an average of two years</time_frame>
    <description>Mean change in QOL scores from baseline to day 14 and day 28 after conversion from tacrolimus to Envarsus.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurological Scores</measure>
    <time_frame>through study completion, an average of two years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tacrolimus preference</measure>
    <time_frame>through study completion, an average of two years</time_frame>
    <description>Proportion of patients preferring Envarsus compared with their previous tacrolimus formulation after 28 days of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-adherence</measure>
    <time_frame>through study completion, an average of two years</time_frame>
    <description>Percent of patients reporting non-adherence from baseline to day 14 and 28 after conversion from tacrolimus to Envarsus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental costs</measure>
    <time_frame>through study completion, an average of two years</time_frame>
    <description>Mean incremental costs from baseline to day 28 following conversion to Envarsus.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">40</enrollment>
  <condition>Disorder Related to Renal Transplantation</condition>
  <arm_group>
    <arm_group_label>Tacrolimus XR</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus XR (Envarsus)</intervention_name>
    <description>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.</description>
    <arm_group_label>Tacrolimus XR</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This study will enroll elderly kidney transplant recipients who are at least 60 years of&#xD;
        age and have experienced neurological adverse events while on generic tacrolimus, Prograf,&#xD;
        or Astagraf XL.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject is a recipient of a living donor or deceased donor kidney only transplant&#xD;
&#xD;
          2. Subject is &gt; 60 years of age&#xD;
&#xD;
          3. Subject reports neurological AEs from tacrolimus that include one or more of the&#xD;
             following: insomnia, vertigo, photophobia, mood disturbances, tremor, and/or headache.&#xD;
&#xD;
          4. Patients must be able to understand English and provide written informed consent&#xD;
&#xD;
          5. Patients receiving a stable dose (i.e., no dose adjustments) of immediate-release&#xD;
             tacrolimus (Prograf) or extended-release tacrolimus (Astagraf) for a minimum of 4-7&#xD;
             days at screening&#xD;
&#xD;
          6. Patients with a screening tacrolimus trough level of 3-12 ng/mL, measured between Day&#xD;
             -7 to 0&#xD;
&#xD;
          7. The patient is not scheduled to begin any new medication that could interfere with&#xD;
             tacrolimus blood levels, including prescription and over-the-counter medications,&#xD;
             herbal or food supplements (including grapefruit and pomegranate products)&#xD;
&#xD;
          8. Patients must be willing to commit to and comply with the schedule of study visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Multi-organ transplant&#xD;
&#xD;
          2. Subjects not taking tacrolimus post-transplant&#xD;
&#xD;
          3. Documented Parkinson's disease or dementia&#xD;
&#xD;
          4. Known cause of neurological symptoms other than tacrolimus&#xD;
&#xD;
          5. Patients with significant visual and hearing impairments affecting their ability to&#xD;
             complete the study requirements and assessments&#xD;
&#xD;
          6. Patients with any severe medical condition (including infection) requiring acute or&#xD;
             chronic treatment that in the Investigator's opinion would interfere with study&#xD;
             participation&#xD;
&#xD;
          7. Known non-adherence (defined as documentation in the patient chart of multiple missed&#xD;
             visits and/or medication doses) which in the investigator's opinion would interfere&#xD;
             with the objectives of the study&#xD;
&#xD;
          8. Patients who are taking any acute or chronic medications that may impact reaction&#xD;
             time, memory, or sleep habits, based on Investigator discretion&#xD;
&#xD;
          9. Patients with any form of current drug or alcohol abuse as assessed by the&#xD;
             Investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>April 20, 2020</last_update_submitted>
  <last_update_submitted_qc>April 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
    <investigator_full_name>Patricia West-Thielke</investigator_full_name>
    <investigator_title>Director of Clinical Research</investigator_title>
  </responsible_party>
  <keyword>kidney transplant</keyword>
  <keyword>immunosuppression</keyword>
  <keyword>tacrolimus XR</keyword>
  <keyword>elderly</keyword>
  <keyword>quality of life</keyword>
  <keyword>neurological adverse events</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03263052
org study id: 2017-0400
nct id: NCT03263052
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
observational model: Case-Crossover
time perspective: Prospective
measure: Quality of life (QOL)
time frame: through study completion, an average of two years
description: Mean change in QOL scores from baseline to day 14 and day 28 after conversion from tacrolimus to Envarsus.
measure: Neurological Scores
time frame: through study completion, an average of two years
description: 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.
measure: Tacrolimus preference
time frame: through study completion, an average of two years
description: Proportion of patients preferring Envarsus compared with their previous tacrolimus formulation after 28 days of treatment
measure: Non-adherence
time frame: through study completion, an average of two years
description: Percent of patients reporting non-adherence from baseline to day 14 and 28 after conversion from tacrolimus to Envarsus.
measure: Incremental costs
time frame: through study completion, an average of two years
description: Mean incremental costs from baseline to day 28 following conversion to Envarsus.
arm group label: Tacrolimus XR
intervention type: Drug
intervention name: Tacrolimus XR (Envarsus)
description: 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.
arm group label: Tacrolimus XR
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Illinois at Chicago
investigator full name: Patricia West-Thielke
investigator title: Director of Clinical Research
mesh term: Tacrolimus
sharing ipd: No