<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/NCT01692925</url>
  </required_header>
  <id_info>
    <org_study_id>NN7008-4015</org_study_id>
    <secondary_id>2012-001444-21</secondary_id>
    <secondary_id>U1111-1129-1517</secondary_id>
    <nct_id>NCT01692925</nct_id>
  </id_info>
  <brief_title>Investigation of the Pharmacokinetics of Turoctocog Alfa in Subjects With Haemophilia A</brief_title>
  <official_title>Multi-centre, Open-labelled Trial Investigating the Pharmacokinetics of Four Lots of Turoctocog Alfa in Subjects With Haemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novo Nordisk A/S</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is conducted in Europe. The aim of the trial is to investigate the&#xD;
      pharmacokinetics (the exposure of the trial drug in the body) of four lots of turoctocog alfa&#xD;
      (a human recombinant coagulation factor VIII (FVIII)) in subjects with haemophilia A.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose normalised area under the curve (AUC/actual dose) based on chromogenic assay</measure>
    <time_frame>up to 48 hours after i.v. administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose normalised area under the FVIII activity-time curve (AUC/actual dose) based on one stage clot assay</measure>
    <time_frame>up to 48 hours after i.v. administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental recovery (IR30min) (defined as the peak FVIII level recorded 30 min after injection and reported as[IU/mL]/[IU/kg])</measure>
    <time_frame>up to 48 hours after i.v. administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the FVIII activity-time curve (AUC)</measure>
    <time_frame>up to 48 hours after i.v. administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of FVIII (t½)</measure>
    <time_frame>up to 48 hours after i.v. administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance of FVIII (CL)</measure>
    <time_frame>up to 48 hours after i.v. administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (AEs) including FVIII inhibitors</measure>
    <time_frame>After approximately 3 months (at end of trial)</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Congenital Bleeding Disorder</condition>
  <condition>Haemophilia A</condition>
  <arm_group>
    <arm_group_label>Lot A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lot B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lot C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lot D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>turoctocog alfa</intervention_name>
    <description>Trial product, 2000 IU/vial will be administered as an i.v. (intravenous) bolus injection.</description>
    <arm_group_label>Lot A</arm_group_label>
    <arm_group_label>Lot B</arm_group_label>
    <arm_group_label>Lot C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>turoctocog alfa</intervention_name>
    <description>Trial product, 3000 IU/vial will be administered as an i.v. (intravenous) bolus injection.</description>
    <arm_group_label>Lot D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent obtained before any trial-related activities. Trial-related&#xD;
             activities are any procedures that are carried out as part of the trial, including&#xD;
             activities to determine suitability for the trial&#xD;
&#xD;
          -  Male subjects with the diagnosis of severe haemophilia A (FVIII&lt;1%) from age 18 years&#xD;
&#xD;
          -  Documented history of at least 150 exposure days to any other FVIII products&#xD;
             (prevention or treatment of bleeds)&#xD;
&#xD;
          -  Immunocompetent (HIV (Human Immunodeficiency Virus) positive subjects should have CD4+&#xD;
             (Cluster of differentiation 4; a glycoprotein expressed on the surface) lymphocyte&#xD;
             count &gt;200/microL)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Detectable inhibitors to FVIII (above or equal to 0.6 Bethesda Units (BU))&#xD;
&#xD;
          -  History of FVIII inhibitors&#xD;
&#xD;
          -  Severe current hepatic dysfunction or severe hepatic disease during the last 12 months&#xD;
&#xD;
          -  Known or suspected allergy to trial product (FVIII) or related products&#xD;
&#xD;
          -  Subjects receiving immune modulating medication or immune tolerance induction (ITI)&#xD;
             regimens&#xD;
&#xD;
          -  Body mass index (BMI) above 30 kg/m^2&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Registry (GCR, 1452)</last_name>
    <role>Study Director</role>
    <affiliation>Novo Nordisk A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10249</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Frankfurt/M.</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Riga</city>
        <zip>1006</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50400</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Latvia</country>
    <country>Malaysia</country>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://novonordisk-trials.com</url>
    <description>Clinical Trials at Novo Nordisk</description>
  </link>
  <results_reference>
    <citation>Jimenez-Yuste V, Lejniece S, Klamroth R, Suzuki T, Santagostino E, Karim FA, Saugstrup T, Moss J. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight(R)), in patients with hemophilia A. J Thromb Haemost. 2015 Mar;13(3):370-9. doi: 10.1111/jth.12816. Epub 2015 Feb 13.</citation>
    <PMID>25495795</PMID>
  </results_reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>February 9, 2017</last_update_submitted>
  <last_update_submitted_qc>February 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2017</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>Hemostatic Disorders</mesh_term>
    <mesh_term>Hemophilia A</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Factor VIII</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/NCT01692925
org study id: NN7008-4015
secondary id: 2012-001444-21
secondary id: U1111-1129-1517
nct id: NCT01692925
lead sponsor: 
has dmc: No
This trial is conducted in Europe. The aim of the trial is to investigate the
      pharmacokinetics (the exposure of the trial drug in the body) of four lots of turoctocog alfa
      (a human recombinant coagulation factor VIII (FVIII)) in subjects with haemophilia A.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose normalised area under the curve (AUC/actual dose) based on chromogenic assay
time frame: up to 48 hours after i.v. administration
measure: Dose normalised area under the FVIII activity-time curve (AUC/actual dose) based on one stage clot assay
time frame: up to 48 hours after i.v. administration
measure: Incremental recovery (IR30min) (defined as the peak FVIII level recorded 30 min after injection and reported as[IU/mL]/[IU/kg])
time frame: up to 48 hours after i.v. administration
measure: Area under the FVIII activity-time curve (AUC)
time frame: up to 48 hours after i.v. administration
measure: Terminal half-life of FVIII (t½)
time frame: up to 48 hours after i.v. administration
measure: Clearance of FVIII (CL)
time frame: up to 48 hours after i.v. administration
measure: Incidence of adverse events (AEs) including FVIII inhibitors
time frame: After approximately 3 months (at end of trial)
arm group label: Lot A
arm group type: Experimental
description: Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.
arm group label: Lot B
arm group type: Experimental
description: Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.
arm group label: Lot C
arm group type: Experimental
description: Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.
arm group label: Lot D
arm group type: Experimental
description: Each subject will receive two single doses of turocotocog alfa from two lots of trial product on two separate days.
intervention type: Drug
intervention name: turoctocog alfa
description: Trial product, 2000 IU/vial will be administered as an i.v. (intravenous) bolus injection.
arm group label: Lot A
arm group label: Lot B
arm group label: Lot C
intervention type: Drug
intervention name: turoctocog alfa
description: Trial product, 3000 IU/vial will be administered as an i.v. (intravenous) bolus injection.
arm group label: Lot D
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Registry (GCR, 1452)
role: Study Director
affiliation: Novo Nordisk A/S
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Latvia
country: Malaysia
country: Spain
url: http://novonordisk-trials.com
description: Clinical Trials at Novo Nordisk
citation: Jimenez-Yuste V, Lejniece S, Klamroth R, Suzuki T, Santagostino E, Karim FA, Saugstrup T, Moss J. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight(R)), in patients with hemophilia A. J Thromb Haemost. 2015 Mar;13(3):370-9. doi: 10.1111/jth.12816. Epub 2015 Feb 13.
PMID: 25495795
responsible party type: Sponsor
mesh term: Hemostatic Disorders
mesh term: Hemophilia A
mesh term: Blood Coagulation Disorders
mesh term: Factor VIII