<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/NCT04439929</url>
  </required_header>
  <id_info>
    <org_study_id>240648</org_study_id>
    <nct_id>NCT04439929</nct_id>
  </id_info>
  <brief_title>Comparative Pharmacokinetic, Safety, Tolerability and Immunogenicity Study of Adalimumab in Healthy Subjects</brief_title>
  <official_title>A Randomized, Double-blind, Two-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Two Formulations of Adalimumab (TUR01 and EU Sourced Humira®) in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Turgut İlaçları A.Ş.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Turgut İlaçları A.Ş.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, two-arm, parallel group, single-dose study to demonstrate&#xD;
      pharmacokinetic, safety, tolerability and immunogenicity similarity of biosimilar candidate&#xD;
      TUR01 to EU-sourced Humira® in healthy participants after administration of adalimumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2019</start_date>
  <completion_date type="Actual">January 16, 2020</completion_date>
  <primary_completion_date type="Actual">January 16, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time curve from time 0 to infinity (AUCinf)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
    <description>AUCinf = area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast) + last observed concentration (Ct)/terminal rate constant (λz)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum serum concentration (Cmax)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
    <description>Cmax</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to 336 hours (AUC336)</measure>
    <time_frame>Day 1 - Day 15</time_frame>
    <description>Area under the concentration-time curve from time zero to 14 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to 672 hours (AUC672)</measure>
    <time_frame>Day 1 - Day 29</time_frame>
    <description>Area under the concentration-time curve from time zero to 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to 1008 hours (AUC1008)</measure>
    <time_frame>Day 1 - Day 43</time_frame>
    <description>Area under the concentration-time curve from time zero to 42 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to 1680 hours (AUC1680)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
    <description>Area under the concentration-time curve from time zero to 70 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
    <description>Time to reach the maximum concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution based on the terminal phase (Vz/F)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant (λz)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
    <description>The parameter will be calculated by linear least squares regression analysis using at least 3 non-zero concentrations in the terminal phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life calculated by ln(2)/λz (t½)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CL/F)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCextrap)</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Immunogenicity - Incidence of anti-drug antibodies to adalimumab</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Immunogenicity - Incidence of neutralizing antibodies</measure>
    <time_frame>Day 1 - Day 71</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">168</enrollment>
  <condition>Healthy Participants</condition>
  <arm_group>
    <arm_group_label>Adalimumab-TUR01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Adalimumab-EU</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TUR01</intervention_name>
    <description>Administered as a single 40 mg, subcutaneous dose</description>
    <arm_group_label>Adalimumab-TUR01</arm_group_label>
    <other_name>Adalimumab-Turgut</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab-EU</intervention_name>
    <description>Administered as a single 40 mg, subcutaneous dose</description>
    <arm_group_label>Adalimumab-EU</arm_group_label>
    <other_name>Humira</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy female subjects of non-childbearing potential or healthy male subjects aged 18&#xD;
             to 55 years (inclusive at screening).&#xD;
&#xD;
          -  Have body weight between 65.0 to 90.0 kg and a body mass index between 20.0 to 29.9&#xD;
             kg/m2, inclusive.&#xD;
&#xD;
          -  Must be willing and able to comply with scheduled visits, treatment plan, laboratory&#xD;
             tests and other study procedures.&#xD;
&#xD;
          -  Must be able to provide written informed consent, which must be obtained prior to any&#xD;
             study related procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant or relevant pathology.&#xD;
&#xD;
          -  Have either active or latent tuberculosis.&#xD;
&#xD;
          -  Have received treatment with a monoclonal antibody or fusion protein within 9 months&#xD;
             prior to administration and/or have evidence of immunogenicity from previous exposure&#xD;
             to a monoclonal antibody or fusion protein.&#xD;
&#xD;
          -  Have a mental disease classified as serious by the Investigator.&#xD;
&#xD;
          -  Have received live vaccine(s) within 4 weeks prior to Screening or who will require&#xD;
             live vaccine(s) between Screening and the final study visit.&#xD;
&#xD;
          -  Who intake alcoholic beverages more than 28 units per week.&#xD;
&#xD;
          -  Have taken medication with a half-life of &gt; 24 h within 4 weeks or 10 half-lives of&#xD;
             the medication prior to investigational medicinal product administration.&#xD;
&#xD;
          -  Have donated &gt; 100 mL of blood or plasma within 4 weeks prior to investigational&#xD;
             medicinal product administration.&#xD;
&#xD;
          -  Have participated in another study with an investigational drug within 4 weeks prior&#xD;
             to investigational medicinal product administration. Subjects who have received&#xD;
             treatment with a biological or immunosuppressive agent within 3 months of screening&#xD;
             should also be excluded.&#xD;
&#xD;
          -  Subjects who are not able to consume standardized meals provided by the clinical study&#xD;
             site during hospitalization.&#xD;
&#xD;
          -  Subjects who, in the opinion of the Investigator, are not likely to complete the study&#xD;
             for whatever reason.&#xD;
&#xD;
          -  Involvement of any sponsor, study site/contract research organisation employee,&#xD;
             Investigator or their close relatives.&#xD;
&#xD;
          -  Vulnerable subjects.&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rainard Fuhr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parexel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PAREXEL International GmbH, Early Phase Clinical Unit Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>14050</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>June 17, 2020</last_update_submitted>
  <last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>adalimumab</keyword>
  <keyword>biosimilar</keyword>
  <keyword>healthy</keyword>
  <keyword>phase 1</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>bioequivalence</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</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/NCT04439929
org study id: 240648
nct id: NCT04439929
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a randomized, double-blind, two-arm, parallel group, single-dose study to demonstrate
      pharmacokinetic, safety, tolerability and immunogenicity similarity of biosimilar candidate
      TUR01 to EU-sourced Humira® in healthy participants after administration of adalimumab.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Area under the concentration-time curve from time 0 to infinity (AUCinf)
time frame: Day 1 - Day 71
description: AUCinf = area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast) + last observed concentration (Ct)/terminal rate constant (λz)
measure: Maximum serum concentration (Cmax)
time frame: Day 1 - Day 71
description: Cmax
measure: Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)
time frame: Day 1 - Day 71
measure: Area under the concentration-time curve from time zero to 336 hours (AUC336)
time frame: Day 1 - Day 15
description: Area under the concentration-time curve from time zero to 14 days
measure: Area under the concentration-time curve from time zero to 672 hours (AUC672)
time frame: Day 1 - Day 29
description: Area under the concentration-time curve from time zero to 28 days
measure: Area under the concentration-time curve from time zero to 1008 hours (AUC1008)
time frame: Day 1 - Day 43
description: Area under the concentration-time curve from time zero to 42 days
measure: Area under the concentration-time curve from time zero to 1680 hours (AUC1680)
time frame: Day 1 - Day 71
description: Area under the concentration-time curve from time zero to 70 days
measure: Time to Cmax (Tmax)
time frame: Day 1 - Day 71
description: Time to reach the maximum concentration
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
time frame: Day 1 - Day 71
measure: Terminal rate constant (λz)
time frame: Day 1 - Day 71
description: The parameter will be calculated by linear least squares regression analysis using at least 3 non-zero concentrations in the terminal phase
measure: Terminal half-life calculated by ln(2)/λz (t½)
time frame: Day 1 - Day 71
measure: Apparent total body clearance (CL/F)
time frame: Day 1 - Day 71
measure: Area under the concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCextrap)
time frame: Day 1 - Day 71
measure: Immunogenicity - Incidence of anti-drug antibodies to adalimumab
time frame: Day 1 - Day 71
measure: Immunogenicity - Incidence of neutralizing antibodies
time frame: Day 1 - Day 71
arm group label: Adalimumab-TUR01
arm group type: Experimental
arm group label: Adalimumab-EU
arm group type: Active Comparator
intervention type: Biological
intervention name: TUR01
description: Administered as a single 40 mg, subcutaneous dose
arm group label: Adalimumab-TUR01
other name: Adalimumab-Turgut
intervention type: Biological
intervention name: Adalimumab-EU
description: Administered as a single 40 mg, subcutaneous dose
arm group label: Adalimumab-EU
other name: Humira
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rainard Fuhr
role: Principal Investigator
affiliation: Parexel
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Adalimumab