<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/NCT03229265</url>
  </required_header>
  <id_info>
    <org_study_id>1606017355</org_study_id>
    <nct_id>NCT03229265</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of Tacrolimus and Mycophenolate Mofetil in Kidney Transplant Recipients With Hyperkalemia Receiving Patiromer</brief_title>
  <official_title>Pharmacokinetic Study of Tacrolimus and Mycophenolate Mofetil in Kidney Transplant Recipients With Hyperkalemia Receiving Patiromer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Rogosin Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Rogosin Institute</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>
      Hyperkalemia (high potassium in blood) is a common condition found in kidney transplant&#xD;
      patients. Risk factors include poor kidney function and exposure to various drugs. Regardless&#xD;
      of the causes, current treatment options are limited. Previously, the only available&#xD;
      potassium binder for lowering potassium in the blood is sodium polystyrene sulfonate, which&#xD;
      has unknown drug interaction profile with transplant medications. Patiromer is a newly&#xD;
      approved potassium binder indicated for the treatment of hyperkalemia. Kidney transplant&#xD;
      patients with hyperkalemia may benefit from patiromer. However, the interaction of patiromer&#xD;
      and transplant medications has not been studied. The goal of this study is to look into the&#xD;
      drug interactions between patiromer and transplant medications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label single center pharmacokinetic study of kidney transplant recipients&#xD;
      with hyperkalemia receiving tacrolimus and MMF-based immunosuppression.&#xD;
&#xD;
      Subjects will be screened for inclusion and exclusion criteria during the screening visit.&#xD;
      There will be 2 study visits (visit 0 and visit 1) for each subject after successful&#xD;
      screening. Visit 0 occurs within 14 days (± 3 days) after screening. Visit 1 occurs at 7 days&#xD;
      (± 3 days) after visit 0. There will be 3 clinical visits (standard of care) after visit 1. A&#xD;
      total of 6 visits are anticipated for this study.&#xD;
&#xD;
      Standard diet for lunch and dinner will be provided to subjects during visit 0 and visit 1.&#xD;
      Meals provided will be monitored in relationship to C0 and C12.&#xD;
&#xD;
      During screening visit, blood tests for baseline BMP, aldosterone, magnesium, tacrolimus,&#xD;
      DSA, and MMF will be obtained. If applicable, concomitant fludrocortiosone will be stopped&#xD;
      prior to screening.&#xD;
&#xD;
      During visit 0, tacrolimus levels will be drawn immediately before (0 hr) and at 8 intervals&#xD;
      after dosing (1,2,3,4,5,6,9,12 hrs). MMF levels will be drawn immediately before (0 hr) and&#xD;
      at 9 intervals after dosing (1,2,3,4,5,6,7,9,12 hrs). Basic metabolic profile and serum&#xD;
      magnesium levels will be drawn immediately before tacrolimus dosing. Oral MMF and tacrolimus&#xD;
      will be dosed at 8am ± 1hr.&#xD;
&#xD;
      Enrollment is defined as the first day when subject receives patiromer treatment. Patiromer&#xD;
      (8.4 grams) will be taken daily at 3 hours after oral tacrolimus and MMF dosing by subjects&#xD;
      commencing 3 days (± 1 day) prior to visit 1. No tacrolimus or MMF dosing changes are allowed&#xD;
      between visit 0 and 1. The addition of new concomitant drugs causing interactions with&#xD;
      tacrolimus and MMF are prohibited between visit 0 and 1.&#xD;
&#xD;
      During visit 1, subjects will follow the same protocol of blood draws as visit 0. Tacrolimus&#xD;
      levels will be drawn immediately before (0 hr) and at 8 intervals after tacrolimus dosing&#xD;
      (1,2,3,4,5,6,9,12 hrs). MMF levels will be drawn immediately before (0 hr) and at 9 intervals&#xD;
      after MMF dosing (1,2,3,4,5,6,7,9,12 hrs). Basic metabolic profile and serum magnesium levels&#xD;
      will be drawn immediately before tacrolimus dosing. Patiromer at 8.4 grams will be given 3&#xD;
      hrs after tacrolimus and MMF dosing. Oral MMF and tacrolimus will be dosed at 8am ± 1hr.&#xD;
&#xD;
      All subjects will followup for clinical visits (2-4) with the PI or their transplant&#xD;
      nephrologists after visit 1 according to schedule (see appendix for study visit events).&#xD;
      Subjects will complete study by 30 days (± 7 days) after visit 0. Adjustment of patiromer&#xD;
      dosing is at the discretion of PIs after visit 2. After completion of study visits, subjects&#xD;
      will continue to follow with transplant clinic monthly for 2 months or sooner if clinically&#xD;
      indicated per the discretion of the treating transplant nephrologist. After 2 months, clinic&#xD;
      visits will be conducted per routine clinic schedule.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">August 7, 2019</completion_date>
  <primary_completion_date type="Actual">August 7, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>Within 30 days</time_frame>
    <description>Investigate the pharmacokinetics of tacrolimus and mycophenolate mofetil in kidney transplant recipients receiving patiromer. Investigators will obtain serum levels of tacrolimus and mycophenolate mofetil before and after the administration of the study drug patiromer. Investigators will measure the areas under the curve of tacrolimus and mycophenolate mofetil before and after exposure to patiromer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum potassium levels</measure>
    <time_frame>Within 30 days</time_frame>
    <description>To assess the effect of patiromer in reducing hyperkalemia. Investigators will measure the serum potassium levels after the administration of the study drug patiromer.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Hyperkalemia</condition>
  <condition>Kidney Transplant</condition>
  <arm_group>
    <arm_group_label>Patiromer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Patiromer</intervention_name>
    <description>Patiromer (8.4 grams) will be taken daily at 3 hours after oral tacrolimus and MMF dosing by subjects commencing 3 days (± 1 day) prior to visit 1.</description>
    <arm_group_label>Patiromer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, 18 years of age or older.&#xD;
&#xD;
          2. Patient is capable of understanding the purposes and risks of the study, who can give&#xD;
             written informed consent and who are willing to participate in and comply with the&#xD;
             study.&#xD;
&#xD;
          3. Kidney transplant recipient.&#xD;
&#xD;
          4. Must be receiving MMF for maintenance immunosuppression&#xD;
&#xD;
          5. Must be receiving tacrolimus for maintenance immunosuppression&#xD;
&#xD;
          6. Subjects must have hyperkalemia (serum potassium ≥ 5.0 mEq/L and ≤ 6.0 mEq/L).&#xD;
&#xD;
          7. Prior to enrollment, subjects must be taking a steady dose of tacrolimus for 3 days.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of Kayexalate 1 day prior to screening visit.&#xD;
&#xD;
          2. Serum potassium level of greater than 6.0 mEq/L at screening.&#xD;
&#xD;
          3. Serum magnesium level of less than 1.0mg/dL at screening.&#xD;
&#xD;
          4. Acute rejection episode within 30 days prior to enrollment.&#xD;
&#xD;
          5. Anemia with hemoglobin level of ≤ 9.0 g/dL prior to screening.&#xD;
&#xD;
          6. Patient has hypersensitivity to patiromer.&#xD;
&#xD;
          7. Receiving maintenance corticosteroid for immunosuppression&#xD;
&#xD;
          8. Serious medical (including history of cardiac arrhythmias) or psychiatric illness&#xD;
             likely to interfere with participation in this clinical study.&#xD;
&#xD;
          9. Patients with known donor-specific antibodies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jun Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Rogosin Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Rogosin Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</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>June 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>April 9, 2020</last_update_submitted>
  <last_update_submitted_qc>April 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkalemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03229265
org study id: 1606017355
nct id: NCT03229265
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Hyperkalemia (high potassium in blood) is a common condition found in kidney transplant
      patients. Risk factors include poor kidney function and exposure to various drugs. Regardless
      of the causes, current treatment options are limited. Previously, the only available
      potassium binder for lowering potassium in the blood is sodium polystyrene sulfonate, which
      has unknown drug interaction profile with transplant medications. Patiromer is a newly
      approved potassium binder indicated for the treatment of hyperkalemia. Kidney transplant
      patients with hyperkalemia may benefit from patiromer. However, the interaction of patiromer
      and transplant medications has not been studied. The goal of this study is to look into the
      drug interactions between patiromer and transplant medications.
This is an open-label single center pharmacokinetic study of kidney transplant recipients
      with hyperkalemia receiving tacrolimus and MMF-based immunosuppression.

      Subjects will be screened for inclusion and exclusion criteria during the screening visit.
      There will be 2 study visits (visit 0 and visit 1) for each subject after successful
      screening. Visit 0 occurs within 14 days (± 3 days) after screening. Visit 1 occurs at 7 days
      (± 3 days) after visit 0. There will be 3 clinical visits (standard of care) after visit 1. A
      total of 6 visits are anticipated for this study.

      Standard diet for lunch and dinner will be provided to subjects during visit 0 and visit 1.
      Meals provided will be monitored in relationship to C0 and C12.

      During screening visit, blood tests for baseline BMP, aldosterone, magnesium, tacrolimus,
      DSA, and MMF will be obtained. If applicable, concomitant fludrocortiosone will be stopped
      prior to screening.

      During visit 0, tacrolimus levels will be drawn immediately before (0 hr) and at 8 intervals
      after dosing (1,2,3,4,5,6,9,12 hrs). MMF levels will be drawn immediately before (0 hr) and
      at 9 intervals after dosing (1,2,3,4,5,6,7,9,12 hrs). Basic metabolic profile and serum
      magnesium levels will be drawn immediately before tacrolimus dosing. Oral MMF and tacrolimus
      will be dosed at 8am ± 1hr.

      Enrollment is defined as the first day when subject receives patiromer treatment. Patiromer
      (8.4 grams) will be taken daily at 3 hours after oral tacrolimus and MMF dosing by subjects
      commencing 3 days (± 1 day) prior to visit 1. No tacrolimus or MMF dosing changes are allowed
      between visit 0 and 1. The addition of new concomitant drugs causing interactions with
      tacrolimus and MMF are prohibited between visit 0 and 1.

      During visit 1, subjects will follow the same protocol of blood draws as visit 0. Tacrolimus
      levels will be drawn immediately before (0 hr) and at 8 intervals after tacrolimus dosing
      (1,2,3,4,5,6,9,12 hrs). MMF levels will be drawn immediately before (0 hr) and at 9 intervals
      after MMF dosing (1,2,3,4,5,6,7,9,12 hrs). Basic metabolic profile and serum magnesium levels
      will be drawn immediately before tacrolimus dosing. Patiromer at 8.4 grams will be given 3
      hrs after tacrolimus and MMF dosing. Oral MMF and tacrolimus will be dosed at 8am ± 1hr.

      All subjects will followup for clinical visits (2-4) with the PI or their transplant
      nephrologists after visit 1 according to schedule (see appendix for study visit events).
      Subjects will complete study by 30 days (± 7 days) after visit 0. Adjustment of patiromer
      dosing is at the discretion of PIs after visit 2. After completion of study visits, subjects
      will continue to follow with transplant clinic monthly for 2 months or sooner if clinically
      indicated per the discretion of the treating transplant nephrologist. After 2 months, clinic
      visits will be conducted per routine clinic schedule.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC
time frame: Within 30 days
description: Investigate the pharmacokinetics of tacrolimus and mycophenolate mofetil in kidney transplant recipients receiving patiromer. Investigators will obtain serum levels of tacrolimus and mycophenolate mofetil before and after the administration of the study drug patiromer. Investigators will measure the areas under the curve of tacrolimus and mycophenolate mofetil before and after exposure to patiromer.
measure: Serum potassium levels
time frame: Within 30 days
description: To assess the effect of patiromer in reducing hyperkalemia. Investigators will measure the serum potassium levels after the administration of the study drug patiromer.
arm group label: Patiromer
arm group type: Experimental
intervention type: Drug
intervention name: Patiromer
description: Patiromer (8.4 grams) will be taken daily at 3 hours after oral tacrolimus and MMF dosing by subjects commencing 3 days (± 1 day) prior to visit 1.
arm group label: Patiromer
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Lee, MD
role: Principal Investigator
affiliation: The Rogosin Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hyperkalemia
sharing ipd: Undecided