<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/NCT03241043</url>
  </required_header>
  <id_info>
    <org_study_id>PAKT CTC 151043</org_study_id>
    <nct_id>NCT03241043</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Pharmacokinetic and Bioavailability of Envarsus® vs. Advagraf® in Liver Transplant Recipients</brief_title>
  <official_title>Single Center, Open-label, Randomized, Controlled, Cross Over Study to Evaluate the Pharmacokinetic and Bioavailability of Envarsus® in Comparison to Advagraf® in de Novo Liver Transplant Recipients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitätsklinikum Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitätsklinikum Hamburg-Eppendorf</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Single centre, open-label, randomized, controlled, cross over study to evaluate the&#xD;
      pharmacokinetic and bioavailability of Envarsus® in comparison to Advagraf® in de novo liver&#xD;
      transplant recipients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using an open-label, randomized, controlled, 2-period cross-over design, two treatments&#xD;
      (Envarsus® and Advagraf®) will be compared (with regard to PK profile and bioavailability)&#xD;
      after administration of IMP to 20 de novo transplanted recipients. The patients will be&#xD;
      randomly assigned to one of the two treatments as treatment period 1 and afterwards switched&#xD;
      to treatment period 2 (Group 1: Envarsus® - Advagraf®; Group 2: Advagraf® - Envarsus®).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2016</start_date>
  <completion_date type="Actual">April 2019</completion_date>
  <primary_completion_date type="Actual">April 2019</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DAV (average cumulative dose) = cumulative dose per study period/ period days</measure>
    <time_frame>20 month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>C0/doses (trough level at steady state / daily dose at steady state)</measure>
    <time_frame>20 month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-24/doses</measure>
    <time_frame>20 month</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Liver Transplantation</condition>
  <arm_group>
    <arm_group_label>Envarsus - Advagraf</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Advagraf - Envarsus</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment 2 weeks Envarsus followed by 2 weeks Advagraf</intervention_name>
    <arm_group_label>Envarsus - Advagraf</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment 2 weeks Advagraf followed by 2 weeks Envarsus</intervention_name>
    <arm_group_label>Advagraf - Envarsus</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to understand the patient information and to personally sign and date the&#xD;
             informed consent to participate in the clinical trial, before completing any clinical&#xD;
             trial related procedures.&#xD;
&#xD;
          2. Male or female recipients ≥ 18 years of a liver graft from a deceased or living donor&#xD;
&#xD;
          3. The patient must receive a twice daily Tacrolimus based immunosuppression treatment.&#xD;
&#xD;
          4. Females of child-bearing potential who agree to comply with any applicable&#xD;
             contraceptive requirements of the protocol or females who are permanently sterilized&#xD;
             (at least 6 weeks post sterilization).&#xD;
&#xD;
          5. Non-pregnant, non-lactating female.&#xD;
&#xD;
          6. Recipients of a first or re-liver transplant in the last 30 days&#xD;
&#xD;
          7. The patient is co-operative and available for the entire clinical trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a known hypersensitivity to any of the drugs used in the study.&#xD;
&#xD;
          2. Patients who are not able to take oral medication at the time point of randomization.&#xD;
&#xD;
          3. Recipients of combined organ transplants.&#xD;
&#xD;
          4. Patients who are recipients of AB0 incompatible transplant grafts.&#xD;
&#xD;
          5. Currently participation in a clinical trial and any IMP intake within the last four&#xD;
             weeks.&#xD;
&#xD;
          6. Patients who use drugs known to strongly interact with the cytochrome P-450 3A4&#xD;
             pathway and therefore influence the tacrolimus blood level are not allowed during&#xD;
             Envarsus®/Advagraf® treatment period.&#xD;
&#xD;
          7. Patient with renal impairment with need of dialysis treatment at the time point of&#xD;
             randomization.&#xD;
&#xD;
          8. Patient with a quick value &lt; 30 %&#xD;
&#xD;
          9. Patient with a thrombocytopenia &lt;20 Mrd./L&#xD;
&#xD;
         10. Patients with a leukopenia &lt; 1.0 Mrd. / L&#xD;
&#xD;
         11. Patients with inability of oral food intake.&#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>Herden</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Hamburg-Eppendorf</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>September 12, 2016</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>May 3, 2021</last_update_submitted>
  <last_update_submitted_qc>May 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetic study</keyword>
  <keyword>Comparing Envarsus versus Advagraf</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03241043
org study id: PAKT CTC 151043
nct id: NCT03241043
lead sponsor: 
has dmc: No
Single centre, open-label, randomized, controlled, cross over study to evaluate the
      pharmacokinetic and bioavailability of Envarsus® in comparison to Advagraf® in de novo liver
      transplant recipients
Using an open-label, randomized, controlled, 2-period cross-over design, two treatments
      (Envarsus® and Advagraf®) will be compared (with regard to PK profile and bioavailability)
      after administration of IMP to 20 de novo transplanted recipients. The patients will be
      randomly assigned to one of the two treatments as treatment period 1 and afterwards switched
      to treatment period 2 (Group 1: Envarsus® - Advagraf®; Group 2: Advagraf® - Envarsus®).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DAV (average cumulative dose) = cumulative dose per study period/ period days
time frame: 20 month
measure: C0/doses (trough level at steady state / daily dose at steady state)
time frame: 20 month
measure: AUC0-24/doses
time frame: 20 month
arm group label: Envarsus - Advagraf
arm group type: Experimental
arm group label: Advagraf - Envarsus
arm group type: Active Comparator
intervention type: Drug
intervention name: Treatment 2 weeks Envarsus followed by 2 weeks Advagraf
arm group label: Envarsus - Advagraf
intervention type: Drug
intervention name: Treatment 2 weeks Advagraf followed by 2 weeks Envarsus
arm group label: Advagraf - Envarsus
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Herden
role: Principal Investigator
affiliation: Universitätsklinikum Hamburg-Eppendorf
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Tacrolimus