<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/NCT02221583</url>
  </required_header>
  <id_info>
    <org_study_id>ASTA-14B02</org_study_id>
    <nct_id>NCT02221583</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Immunosuppressants in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy</brief_title>
  <official_title>A Multicenter Pilot Study to Determine the Pharmacokinetics of Astagraf XL, Prograf and Mycophenolate Mofetil in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cincinnati</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate how quickly and to what extent different&#xD;
      immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal&#xD;
      transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system&#xD;
      is the body's defense against diseases. It also attacks &quot;foreign&quot; tissues such as a&#xD;
      transplanted kidney. Immunosuppressant medications such as Astagraf sustained release (XL),&#xD;
      Prograf, and mycophenolate mofetil may be given to suppress the immune system following&#xD;
      kidney transplantation and prevent rejection of a transplanted kidney. This study is being&#xD;
      performed to determine if patients who undergo laparoscopic sleeve gastrectomy need different&#xD;
      doses of immunosuppressant medications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators propose a single dose, cross over pharmacokinetic study of Astagraf XL and&#xD;
      Prograf® in combination with MMF in RTx candidates that have undergone LSG. Subjects at least&#xD;
      three months post LSG and pre-renal transplant will undergo preliminary screening. The study&#xD;
      population will consist of 24 male and female subjects, ≥ 18 years old from UC Health&#xD;
      University Hospital and The Christ Hospital who meet the inclusion/exclusion criteria.&#xD;
&#xD;
      Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf&#xD;
      XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A&#xD;
      full 24 hour PK profile will be constructed. After at least a one week washout period, the&#xD;
      patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or&#xD;
      Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. The&#xD;
      immunosuppressants chosen reflect the regimen most commonly prescribed to transplant&#xD;
      recipients.&#xD;
&#xD;
      Subjects participating in the study will have pharmacokinetic blood samples drawn over a 24&#xD;
      hour time period in order to determine the AUC, Tmax, Cmax, and half-life of tacrolimus, MMF&#xD;
      and their metabolites. Samples would be drawn prior to dosing (C0) and at 1, 1.5, 2, 2.5, 3,&#xD;
      4, 6, 8, 12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing (18 time points) by&#xD;
      venipuncture or IV.&#xD;
&#xD;
      This study proposal represents a simple and expeditious method to achieve PK information in&#xD;
      patients that have undergone LSG. If desired, study could be expanded to evaluate PK in&#xD;
      additional patient groups such as pre and post LSG and/or pre and post renal transplant. The&#xD;
      exact sample collection time will be recorded in the case report form. All deviations from&#xD;
      the scheduled sampling time of more than 5 minutes for the first 4 hours after the AM dose&#xD;
      (predose-4 hr) and first 4 hours of the PM dose (12 hr-16 hr), and more than 10 minutes for&#xD;
      all remaining samples (6 hr-8 hr; 18 hr-24 hr) will be reported as a protocol deviation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under Curve (AUC)</measure>
    <time_frame>Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing</time_frame>
    <description>AUC of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum concentration (Cmax)</measure>
    <time_frame>Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing</time_frame>
    <description>Cmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to maximum concentration (Tmax)</measure>
    <time_frame>Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing</time_frame>
    <description>Tmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Half life (T 1/2)</measure>
    <time_frame>24 hours</time_frame>
    <description>Half-life of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events (serious and non-serious)</measure>
    <time_frame>Study Day 1 and Day 8</time_frame>
    <description>All serious adverse events and non-serious adverse events as reported by the subject will be recorded</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>End Stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Astagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Astagraf XL</intervention_name>
    <description>Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Tacrolimus sustained release</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prograf</intervention_name>
    <description>Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Tacrolimus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil</intervention_name>
    <description>Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Cellcept</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female or male patient aged &gt; 18 years old.&#xD;
&#xD;
          2. ESRD patient (on dialysis or preemptive) who is a potential candidate for kidney&#xD;
             transplantation&#xD;
&#xD;
          3. Undergone laparoscopic sleeve gastrectomy procedure &gt; 3 months prior to enrollment.&#xD;
&#xD;
          4. Subjects have signed and dated the informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients taking a drug known to interact with Astagraf XL, Prograf®, or MMF.&#xD;
&#xD;
          2. Patients that have an allergy to Astagraf XL, Prograf®, or MMF.&#xD;
&#xD;
          3. Patients currently taking Astagraf XL, Prograf®, or MMF.&#xD;
&#xD;
          4. Post-surgical leak complication&#xD;
&#xD;
          5. Patients failing to adhere to post laparoscopic sleeve gastrectomy follow-up&#xD;
             recommendations and clinic visits&#xD;
&#xD;
          6. Patients with any severe medical condition requiring acute or chronic treatment that&#xD;
             in the investigator's opinion would interfere with study participation.&#xD;
&#xD;
          7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a&#xD;
             female after conception and until the termination of gestation, confirmed by a&#xD;
             positive laboratory test&#xD;
&#xD;
          8. Currently taking or planning to initiate of any medications that could interfere with&#xD;
             tacrolimus and/or mycophenolate blood levels, including over the counter (OTC)&#xD;
             medications, herbal supplements, grapefruit or grapefruit juice.&#xD;
&#xD;
          9. Subjects who have been exposed to an investigational therapy within 30 days prior to&#xD;
             enrollment or 5 half-lives of the investigational product, whichever is greater.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tayyab Diwan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>May 11, 2015</last_update_submitted>
  <last_update_submitted_qc>May 11, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 12, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Tayyab Diwan</investigator_full_name>
    <investigator_title>Assistant Professor of Surgery</investigator_title>
  </responsible_party>
  <keyword>End stage renal disease</keyword>
  <keyword>Renal transplant candidate</keyword>
  <keyword>Laparoscopic sleeve gastrectomy</keyword>
  <keyword>Immunosuppressants</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>June 30, 2016</submitted>
    <returned>August 9, 2016</returned>
    <submitted>August 20, 2016</submitted>
    <returned>October 13, 2016</returned>
    <submitted>October 26, 2016</submitted>
    <returned>December 27, 2016</returned>
  </pending_results>
  <!-- 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/NCT02221583
org study id: ASTA-14B02
nct id: NCT02221583
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate how quickly and to what extent different
      immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal
      transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system
      is the body's defense against diseases. It also attacks "foreign" tissues such as a
      transplanted kidney. Immunosuppressant medications such as Astagraf sustained release (XL),
      Prograf, and mycophenolate mofetil may be given to suppress the immune system following
      kidney transplantation and prevent rejection of a transplanted kidney. This study is being
      performed to determine if patients who undergo laparoscopic sleeve gastrectomy need different
      doses of immunosuppressant medications.
Investigators propose a single dose, cross over pharmacokinetic study of Astagraf XL and
      Prograf® in combination with MMF in RTx candidates that have undergone LSG. Subjects at least
      three months post LSG and pre-renal transplant will undergo preliminary screening. The study
      population will consist of 24 male and female subjects, ≥ 18 years old from UC Health
      University Hospital and The Christ Hospital who meet the inclusion/exclusion criteria.

      Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf
      XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A
      full 24 hour PK profile will be constructed. After at least a one week washout period, the
      patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or
      Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. The
      immunosuppressants chosen reflect the regimen most commonly prescribed to transplant
      recipients.

      Subjects participating in the study will have pharmacokinetic blood samples drawn over a 24
      hour time period in order to determine the AUC, Tmax, Cmax, and half-life of tacrolimus, MMF
      and their metabolites. Samples would be drawn prior to dosing (C0) and at 1, 1.5, 2, 2.5, 3,
      4, 6, 8, 12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing (18 time points) by
      venipuncture or IV.

      This study proposal represents a simple and expeditious method to achieve PK information in
      patients that have undergone LSG. If desired, study could be expanded to evaluate PK in
      additional patient groups such as pre and post LSG and/or pre and post renal transplant. The
      exact sample collection time will be recorded in the case report form. All deviations from
      the scheduled sampling time of more than 5 minutes for the first 4 hours after the AM dose
      (predose-4 hr) and first 4 hours of the PM dose (12 hr-16 hr), and more than 10 minutes for
      all remaining samples (6 hr-8 hr; 18 hr-24 hr) will be reported as a protocol deviation.
allocation: Randomized
intervention model: Crossover Assignment
masking: Double (Participant, Investigator)
measure: Area Under Curve (AUC)
time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
description: AUC of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
measure: Maximum concentration (Cmax)
time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
description: Cmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
measure: Time to maximum concentration (Tmax)
time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
description: Tmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
measure: Half life (T 1/2)
time frame: 24 hours
description: Half-life of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
measure: Adverse events (serious and non-serious)
time frame: Study Day 1 and Day 8
description: All serious adverse events and non-serious adverse events as reported by the subject will be recorded
arm group label: Group 1
arm group type: Experimental
description: Astagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate
arm group label: Group 2
arm group type: Experimental
description: Prograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate
intervention type: Drug
intervention name: Astagraf XL
description: Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
arm group label: Group 1
arm group label: Group 2
other name: Tacrolimus sustained release
intervention type: Drug
intervention name: Prograf
description: Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
arm group label: Group 1
arm group label: Group 2
other name: Tacrolimus
intervention type: Drug
intervention name: Mycophenolate mofetil
description: Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
arm group label: Group 1
arm group label: Group 2
other name: Cellcept
criteria: 
gender: All
minimum age: 19 Years
maximum age: 75 Years
healthy volunteers: No
last name: Tayyab Diwan, MD
role: Principal Investigator
affiliation: University of Cincinnati
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Cincinnati
investigator full name: Tayyab Diwan
investigator title: Assistant Professor of Surgery
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
mesh term: Mycophenolic Acid
mesh term: Tacrolimus
submitted: June 30, 2016
returned: August 9, 2016
submitted: August 20, 2016
returned: October 13, 2016
submitted: October 26, 2016
returned: December 27, 2016