<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/NCT01731600</url>
  </required_header>
  <id_info>
    <org_study_id>NN7088-3885</org_study_id>
    <secondary_id>U1111-1129-6009</secondary_id>
    <secondary_id>2012-001711-23</secondary_id>
    <secondary_id>JapicCTI-132214</secondary_id>
    <nct_id>NCT01731600</nct_id>
  </id_info>
  <brief_title>A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe Haemophilia A</brief_title>
  <acronym>pathfinder™5</acronym>
  <official_title>A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe 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 globally. The aim of the trial is to investigate safety, efficacy and&#xD;
      pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP)&#xD;
      in children with severe haemophilia A who have undergone treatment with previous factor VIII&#xD;
      (FVIII) products.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2013</start_date>
  <completion_date type="Actual">September 28, 2018</completion_date>
  <primary_completion_date type="Actual">September 15, 2014</primary_completion_date>
  <phase>Phase 3</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>Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units</measure>
    <time_frame>During the main phase of the trial (from 0-26 weeks of treatment)</time_frame>
    <description>The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The frequency of adverse events including serious adverse events reported during the main and extension phase of the trial. The data presented is the rate of AE i.e. number of AEs per patient years of exposue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by patient and/or parent(s)/caregiver 8 hours after first injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of N8-GP Per Bleeding Episode (Number of Injections)</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of N8-GP Per Bleeding Episode (U/kg)</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of N8-GP During Prophylaxis (Number of Injections)</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of N8-GP During Prophylaxis (U/kg Per Month)</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per month per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics [PK])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of N8-GP During Prophylaxis (U/kg Per Year)</measure>
    <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
    <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per year per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product</measure>
    <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
    <description>The incremental recovery was defined as the increase in plasma FVIII activity per IU/kg of factor administered recorded 60 minutes after end of injection. It was calculated as (Factor VIII procoagulant [FVIII:C] activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with normal human plasma (NHP) as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP</measure>
    <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP</time_frame>
    <description>The incremental recovery was defined as the peak level recorded 60 min after end of injection and dose-normalised. It was calculated as (FVIII:C activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with product specific calibrator (PSS) as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve Evaluated for Previous FVIII Product</measure>
    <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
    <description>Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve Evaluated for N8-GP</measure>
    <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP</time_frame>
    <description>Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life Evaluated for Previous FVIII Product</measure>
    <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
    <description>t½ = ln(2) / λz, where t½ is terminal half-life and λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the lower limit of quantification (LLOQ). This was estimated using time points from 1h to 30h. A chromogenic assay with PSS as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life Evaluated for N8-GP</measure>
    <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP</time_frame>
    <description>t½ = ln(2) / λz, where λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the LLOQ. This was estimated using time points from 6h to 96h. A chromogenic assay with PSS as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance Evaluated for Previous FVIII Product</measure>
    <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
    <description>Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance Evaluated for N8-GP</measure>
    <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP.</time_frame>
    <description>Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Congenital Bleeding Disorder</condition>
  <condition>Haemophilia A</condition>
  <arm_group>
    <arm_group_label>N8-GP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>turoctocog alfa pegol</intervention_name>
    <description>Fixed dose of turoctocog alfa pegol for intravenous injections (i.v.) twice weekly for prophylaxis. In addition, turoctocog alfa pegol will be administered to treat bleeding episodes during the trial period. Bleeding episodes will be treated with doses of 20-75 U/kg body weight.</description>
    <arm_group_label>N8-GP</arm_group_label>
    <other_name>NNC 0129-0000-1003</other_name>
    <other_name>N8-GP</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patients with severe congenital haemophilia A (FVIII activity level below 1%)&#xD;
&#xD;
          -  Weight above or equal to 10 kg - Documented history of 150 exposure days (ED) to FVIII&#xD;
             products for patients aged 6-11 years and above 50 ED to FVIII products for patients&#xD;
             aged 0-5 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Any history of FVIII inhibitors&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>11 Years</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>Phoenix</city>
        <state>Arizona</state>
        <zip>85016-7710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010-2978</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70118-5720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198-6828</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-9830</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20211-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bron Cedex</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lille</city>
        <zip>59097</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>GR-11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR 54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tel-Hashomer</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Vicenza</city>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kitakyusyu, Fukuoka</city>
        <zip>807 8555</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tokyo</city>
        <zip>167-0035</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08406</zip>
        <country>Lithuania</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>Porto</city>
        <zip>4200-319</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>San Juan</city>
        <zip>00935</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bellinzona</city>
        <zip>6500</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Luzern 16</city>
        <zip>6000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Zürich</city>
        <zip>8032</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Antalya</city>
        <zip>01010</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bornova-IZMIR</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Izmit</city>
        <zip>41380</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Samsun</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Donetsk</city>
        <zip>83045</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lviv</city>
        <zip>79044</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Leicester</city>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Greece</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Lithuania</country>
    <country>Malaysia</country>
    <country>Portugal</country>
    <country>Puerto Rico</country>
    <country>Switzerland</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <link>
    <url>http://novonordisk-trials.com</url>
    <description>Clinical Trials at Novo Nordisk</description>
  </link>
  <results_reference>
    <citation>Tosetto A, Neff A, Lentz SR, Santagostino E, Nemes L, Sathar J, Meijer K, Chowdary P, Shen C, Landorph A, Hampton K. Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials. Haemophilia. 2020 May;26(3):450-458. doi: 10.1111/hae.13980. Epub 2020 Apr 15.</citation>
    <PMID>32293786</PMID>
  </results_reference>
  <results_reference>
    <citation>Saulyte Trakymiene S, Economou M, Kenet G, Landorph A, Shen C, Kearney S. Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5. J Thromb Haemost. 2020 Sep;18 Suppl 1(Suppl 1):15-25. doi: 10.1111/jth.15036.</citation>
    <PMID>32940955</PMID>
  </results_reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <results_first_submitted>September 19, 2019</results_first_submitted>
  <results_first_submitted_qc>October 25, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 30, 2019</results_first_posted>
  <disposition_first_submitted>September 14, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>September 14, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 18, 2018</disposition_first_posted>
  <last_update_submitted>November 3, 2020</last_update_submitted>
  <last_update_submitted_qc>November 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 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>Hemostatic Disorders</mesh_term>
    <mesh_term>Hemophilia A</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 13, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT01731600/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The trial was conducted at 36 sites in 15 countries as follows: Canada (1), France (2), Germany (1), Greece (2 sites screened/1 site randomised subjects), Israel (1), Italy (1), Japan (2), Lithuania (1), Malaysia (1), Portugal (1), Switzerland (3), Turkey (3), Ukraine (2), United Kingdom (3), and United States (12).</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Younger Children (0 - 5 Years)</title>
          <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
        </group>
        <group group_id="P2">
          <title>Older Children (6 - 11 Years)</title>
          <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal criteria</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reasons</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Younger Children (0 - 5 Years)</title>
          <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
        </group>
        <group group_id="B2">
          <title>Older Children (6 - 11 Years)</title>
          <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). Prophylaxis: N8-GP as a single bolus iv injection 60 IU/kg twice weekly. Treatment of bleeding episodes: N8-GP ranging from 20-75 IU/kg, according to severity and location of bleeding episode. The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="34"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="68"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.0" spread="1.3"/>
                    <measurement group_id="B2" value="8.9" spread="1.7"/>
                    <measurement group_id="B3" value="6.0" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Infants and toddlers (28 days-23 months)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Children (2-11 years)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>Race of the participants</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not applicable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units</title>
        <description>The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.</description>
        <time_frame>During the main phase of the trial (from 0-26 weeks of treatment)</time_frame>
        <population>Results were based on safety analysis set (SAS). The SAS consists of all patients exposed to at least one dose of turoctocog alfa pegol. Number analysed = participants with minimum of 50 exposure days and developed inhibitory antibodies</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units</title>
          <description>The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.</description>
          <population>Results were based on safety analysis set (SAS). The SAS consists of all patients exposed to at least one dose of turoctocog alfa pegol. Number analysed = participants with minimum of 50 exposure days and developed inhibitory antibodies</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A one-sided, upper 97.5% confidence limit was provided based on an exact calculation in the binomial distribution.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Incidence rate</param_type>
            <param_value>0</param_value>
            <ci_percent>97.5</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>0.067</ci_upper_limit>
            <estimate_desc>The incidence of inhibitory antibodies was calculated as number of patients with inhibitors during the main phase of the trial divided by number of patients in the main phase of the trial.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period</title>
        <description>The frequency of adverse events including serious adverse events reported during the main and extension phase of the trial. The data presented is the rate of AE i.e. number of AEs per patient years of exposue.</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on SAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period</title>
          <description>The frequency of adverse events including serious adverse events reported during the main and extension phase of the trial. The data presented is the rate of AE i.e. number of AEs per patient years of exposue.</description>
          <population>Results were based on SAS.</population>
          <units>Events per patient years of exposure</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.87"/>
                    <measurement group_id="O2" value="4.74"/>
                    <measurement group_id="O3" value="3.09"/>
                    <measurement group_id="O4" value="2.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None</title>
        <description>Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by patient and/or parent(s)/caregiver 8 hours after first injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on full analysis set (FAS). All trial patients allocated to treatment, for which at least one of the pharmacokinetic or efficacy endpoints was assessed, were included in the FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None</title>
          <description>Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by patient and/or parent(s)/caregiver 8 hours after first injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.</description>
          <population>Results were based on full analysis set (FAS). All trial patients allocated to treatment, for which at least one of the pharmacokinetic or efficacy endpoints was assessed, were included in the FAS.</population>
          <units>Bleeding episodes</units>
          <param>Count of Units</param>
          <units_analyzed>Bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="108"/>
                <count group_id="O4" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Excellent</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="47"/>
                    <measurement group_id="O4" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="48"/>
                    <measurement group_id="O4" value="74"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="9"/>
                    <measurement group_id="O4" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)</title>
        <description>The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)</title>
          <description>The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.</description>
          <population>Results were based on FAS.</population>
          <units>bleeds/patient/year</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.94" lower_limit="0.00" upper_limit="2.08"/>
                    <measurement group_id="O2" value="1.97" lower_limit="0.00" upper_limit="3.91"/>
                    <measurement group_id="O3" value="0.61" lower_limit="0.20" upper_limit="1.19"/>
                    <measurement group_id="O4" value="0.93" lower_limit="0.20" upper_limit="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of N8-GP Per Bleeding Episode (Number of Injections)</title>
        <description>The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed.</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of N8-GP Per Bleeding Episode (Number of Injections)</title>
          <description>The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed.</description>
          <population>Results were based on FAS.</population>
          <units>Number of injections</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="108"/>
                <count group_id="O4" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="1.5"/>
                    <measurement group_id="O2" value="1.6" spread="0.9"/>
                    <measurement group_id="O3" value="1.6" spread="1.3"/>
                    <measurement group_id="O4" value="1.5" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of N8-GP Per Bleeding Episode (U/kg)</title>
        <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of N8-GP Per Bleeding Episode (U/kg)</title>
          <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.</description>
          <population>Results were based on FAS.</population>
          <units>IU/kg/bleed</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="40"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="108"/>
                <count group_id="O4" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="123" spread="104.9"/>
                    <measurement group_id="O2" value="99" spread="54.4"/>
                    <measurement group_id="O3" value="102.8" spread="81"/>
                    <measurement group_id="O4" value="91" spread="58.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of N8-GP During Prophylaxis (Number of Injections)</title>
        <description>The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of N8-GP During Prophylaxis (Number of Injections)</title>
          <description>The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.</description>
          <population>Results were based on FAS.</population>
          <units>Number of injections</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Injections</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Injections</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1592"/>
                <count group_id="O2" value="1799"/>
                <count group_id="O3" value="14442"/>
                <count group_id="O4" value="17243"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.3" spread="6.5"/>
                    <measurement group_id="O2" value="62.3" spread="7.4"/>
                    <measurement group_id="O3" value="65.4" spread="7.5"/>
                    <measurement group_id="O4" value="64.1" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of N8-GP During Prophylaxis (U/kg Per Month)</title>
        <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per month per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics [PK])</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of N8-GP During Prophylaxis (U/kg Per Month)</title>
          <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per month per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics [PK])</description>
          <population>Results were based on FAS.</population>
          <units>U/kg/month</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="572.5" spread="97.4"/>
                    <measurement group_id="O2" value="555.8" spread="44.6"/>
                    <measurement group_id="O3" value="564.9" spread="86.6"/>
                    <measurement group_id="O4" value="563.4" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of N8-GP During Prophylaxis (U/kg Per Year)</title>
        <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per year per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics)</description>
        <time_frame>Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Main Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Main Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days).</description>
          </group>
          <group group_id="O3">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O4">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of N8-GP During Prophylaxis (U/kg Per Year)</title>
          <description>The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per year per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics)</description>
          <population>Results were based on FAS.</population>
          <units>U/kg/year</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6870.3" spread="1169"/>
                    <measurement group_id="O2" value="6669.6" spread="535.8"/>
                    <measurement group_id="O3" value="6778.6" spread="1039"/>
                    <measurement group_id="O4" value="6760.4" spread="181.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product</title>
        <description>The incremental recovery was defined as the increase in plasma FVIII activity per IU/kg of factor administered recorded 60 minutes after end of injection. It was calculated as (Factor VIII procoagulant [FVIII:C] activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with normal human plasma (NHP) as calibrator was used.</description>
        <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product</title>
          <description>The incremental recovery was defined as the increase in plasma FVIII activity per IU/kg of factor administered recorded 60 minutes after end of injection. It was calculated as (Factor VIII procoagulant [FVIII:C] activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with normal human plasma (NHP) as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>(IU/mL)/(U/kg)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.017" lower_limit="0.014" upper_limit="0.021"/>
                    <measurement group_id="O2" value="0.022" lower_limit="0.018" upper_limit="0.027"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP</title>
        <description>The incremental recovery was defined as the peak level recorded 60 min after end of injection and dose-normalised. It was calculated as (FVIII:C activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with product specific calibrator (PSS) as calibrator was used.</description>
        <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP</title>
          <description>The incremental recovery was defined as the peak level recorded 60 min after end of injection and dose-normalised. It was calculated as (FVIII:C activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with product specific calibrator (PSS) as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>(IU/mL)/(U/kg)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.018" lower_limit="0.015" upper_limit="0.022"/>
                    <measurement group_id="O2" value="0.020" lower_limit="0.016" upper_limit="0.024"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Curve Evaluated for Previous FVIII Product</title>
        <description>Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used.</description>
        <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
        <population>Results were based on FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve Evaluated for Previous FVIII Product</title>
          <description>Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used.</description>
          <population>Results were based on FAS</population>
          <units>IU×h/mL</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.628" lower_limit="9.170" upper_limit="14.744"/>
                    <measurement group_id="O2" value="12.203" lower_limit="9.336" upper_limit="15.951"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Curve Evaluated for N8-GP</title>
        <description>Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used.</description>
        <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve Evaluated for N8-GP</title>
          <description>Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>IU*h/mL</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.489" lower_limit="16.785" upper_limit="27.511"/>
                    <measurement group_id="O2" value="25.026" lower_limit="19.145" upper_limit="32.713"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-life Evaluated for Previous FVIII Product</title>
        <description>t½ = ln(2) / λz, where t½ is terminal half-life and λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the lower limit of quantification (LLOQ). This was estimated using time points from 1h to 30h. A chromogenic assay with PSS as calibrator was used.</description>
        <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life Evaluated for Previous FVIII Product</title>
          <description>t½ = ln(2) / λz, where t½ is terminal half-life and λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the lower limit of quantification (LLOQ). This was estimated using time points from 1h to 30h. A chromogenic assay with PSS as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" spread="20.1"/>
                    <measurement group_id="O2" value="7.5" spread="19.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-life Evaluated for N8-GP</title>
        <description>t½ = ln(2) / λz, where λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the LLOQ. This was estimated using time points from 6h to 96h. A chromogenic assay with PSS as calibrator was used.</description>
        <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life Evaluated for N8-GP</title>
          <description>t½ = ln(2) / λz, where λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the LLOQ. This was estimated using time points from 6h to 96h. A chromogenic assay with PSS as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6" spread="20.4"/>
                    <measurement group_id="O2" value="14.1" spread="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clearance Evaluated for Previous FVIII Product</title>
        <description>Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.</description>
        <time_frame>2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Clearance Evaluated for Previous FVIII Product</title>
          <description>Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>mL/h/kg</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.322" lower_limit="3.404" upper_limit="5.486"/>
                    <measurement group_id="O2" value="3.867" lower_limit="2.955" upper_limit="5.061"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clearance Evaluated for N8-GP</title>
        <description>Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.</description>
        <time_frame>From 1 hour prior to and up to 96 hours after initial administration of N8-GP.</time_frame>
        <population>Results were based on FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Younger Children (0 - 5 Years) [Full Trial]</title>
            <description>Participants (0 - 5 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
          <group group_id="O2">
            <title>Older Children (6 - 11 Years) [Full Trial]</title>
            <description>Participants (6 - 11 years) previously treated with FVIII received N8-GP (prophylaxis or treatment of bleeding episodes). The trial consisted of main and extension phase. Duration of main phase for each subject was approximately 26 weeks (50 exposure days). After completion of main phase, subjects could continue until the end of the extension phase, which was defined as LPLV. All subjects continued twice weekly or every third day prophylaxis regimen in extension phase as prescribed for main phase. However, after 12 months treatment with N8-GP (main phase+extension phase) the investigator was permitted to prescribe extra coverage before physical activities.</description>
          </group>
        </group_list>
        <measure>
          <title>Clearance Evaluated for N8-GP</title>
          <description>Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.</description>
          <population>Results were based on FAS.</population>
          <units>mL/h/kg</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.601" lower_limit="2.030" upper_limit="3.333"/>
                    <measurement group_id="O2" value="2.386" lower_limit="1.823" upper_limit="3.123"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first exposure to N8-GP (visit 2) of main phase to end of extension phase (&gt;=4 days after last dose of N8-GP, up to 4.5 years).</time_frame>
      <desc>The safety analysis set consists of all patients exposed to at least one dose of N8-GP.</desc>
      <group_list>
        <group group_id="E1">
          <title>Younger Children£(0-5 Years)</title>
        </group>
        <group group_id="E2">
          <title>Older Children£(6-11 Years)</title>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Sepsis syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hand fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Acquired phimosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Adenoidal hypertrophy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Cerumen impaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis allergic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Chapped lips</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="34"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthermia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Food allergy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" events="13" subjects_affected="9" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="10" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Molluscum contagiosum</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="21" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E2" events="16" subjects_affected="10" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pharyngotonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="34"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="20" subjects_affected="10" subjects_at_risk="34"/>
                <counts group_id="E2" events="31" subjects_affected="13" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Viral pharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Arthropod sting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Face injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="12" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="11" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Skin papilloma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="16" subjects_affected="9" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Attention deficit/hyperactivity disorder</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Penile adhesion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="26" subjects_affected="14" subjects_at_risk="34"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="28" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="11" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Reporting Anchor and Disclosure (1452)</name_or_title>
      <organization>Novo Nordisk A/S</organization>
      <phone>(+1) 866-867-7178</phone>
      <email>clinicaltrials@novonordisk.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01731600
org study id: NN7088-3885
secondary id: U1111-1129-6009
secondary id: 2012-001711-23
secondary id: JapicCTI-132214
nct id: NCT01731600
lead sponsor: 
has dmc: No
This trial is conducted globally. The aim of the trial is to investigate safety, efficacy and
      pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP)
      in children with severe haemophilia A who have undergone treatment with previous factor VIII
      (FVIII) products.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units
time frame: During the main phase of the trial (from 0-26 weeks of treatment)
description: The number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) ≥0.6 Bethesda units was presented.
measure: Frequency of Adverse Events Including Serious Adverse Events Reported During the Trial Period
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The frequency of adverse events including serious adverse events reported during the main and extension phase of the trial. The data presented is the rate of AE i.e. number of AEs per patient years of exposue.
measure: Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes and Assessed as: Excellent, Good, Moderate, or None
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by patient and/or parent(s)/caregiver 8 hours after first injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
measure: Number of Bleeding Episodes During Prophylactic Treatment With N8-GP (Annualised Bleeding Rate)
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.
measure: Consumption of N8-GP Per Bleeding Episode (Number of Injections)
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed.
measure: Consumption of N8-GP Per Bleeding Episode (U/kg)
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed.
measure: Consumption of N8-GP During Prophylaxis (Number of Injections)
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis.
measure: Consumption of N8-GP During Prophylaxis (U/kg Per Month)
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per month per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics [PK])
measure: Consumption of N8-GP During Prophylaxis (U/kg Per Year)
time frame: Main phase: (from 0-26 weeks of treatment) and full trial: (0 weeks to last patient's completion of the trial, an average of 4.5 years)
description: The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed during prophylaxis (per year per subject). Consumption used for treatment includes all doses given (prophylaxis, treatment of bleed, minor surgery and pharmacokinetics)
measure: Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for Previous FVIII Product
time frame: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
description: The incremental recovery was defined as the increase in plasma FVIII activity per IU/kg of factor administered recorded 60 minutes after end of injection. It was calculated as (Factor VIII procoagulant [FVIII:C] activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with normal human plasma (NHP) as calibrator was used.
measure: Incremental Recovery (Defined as the Peak Level Recorded 60 Min After End of Injection) Evaluated for N8-GP
time frame: From 1 hour prior to and up to 96 hours after initial administration of N8-GP
description: The incremental recovery was defined as the peak level recorded 60 min after end of injection and dose-normalised. It was calculated as (FVIII:C activity measured in plasma 60 min after dosing - FVIII:C activity measured in plasma immediately before dosing) / (dose injected at time 0 min), where the dose was expressed as U FVIII product per kg body weight. A chromogenic assay with product specific calibrator (PSS) as calibrator was used.
measure: Area Under the Curve Evaluated for Previous FVIII Product
time frame: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
description: Area under the curve (AUC) versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with NHP as calibrator was used.
measure: Area Under the Curve Evaluated for N8-GP
time frame: From 1 hour prior to and up to 96 hours after initial administration of N8-GP
description: Area under the curve versus time from zero to infinity. This is calculated as AUC = AUClast + (C(t) / λz), where C(t) is the last measurable concentration. A chromogenic assay with product specific standard (PSS) as calibrator was used.
measure: Terminal Half-life Evaluated for Previous FVIII Product
time frame: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
description: t½ = ln(2) / λz, where t½ is terminal half-life and λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the lower limit of quantification (LLOQ). This was estimated using time points from 1h to 30h. A chromogenic assay with PSS as calibrator was used.
measure: Terminal Half-life Evaluated for N8-GP
time frame: From 1 hour prior to and up to 96 hours after initial administration of N8-GP
description: t½ = ln(2) / λz, where λz is the terminal elimination rate. The terminal elimination rate was planned estimated using linear regression on the terminal part of the time versus log(concentration) curve. A population-based method simultaneously estimating individual t½ values for all patients was applied, including patients with few values above the LLOQ. This was estimated using time points from 6h to 96h. A chromogenic assay with PSS as calibrator was used.
measure: Clearance Evaluated for Previous FVIII Product
time frame: 2-6 weeks prior to initial dosing with N8-GP and up to 30 hours after administration of previous FVIII product
description: Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with NHP as calibrator was used.
measure: Clearance Evaluated for N8-GP
time frame: From 1 hour prior to and up to 96 hours after initial administration of N8-GP.
description: Total plasma clearance of drug after intravenous administration measured as actual dose/AUC. A chromogenic assay with PSS as calibrator was used.
arm group label: N8-GP
arm group type: Experimental
intervention type: Drug
intervention name: turoctocog alfa pegol
description: Fixed dose of turoctocog alfa pegol for intravenous injections (i.v.) twice weekly for prophylaxis. In addition, turoctocog alfa pegol will be administered to treat bleeding episodes during the trial period. Bleeding episodes will be treated with doses of 20-75 U/kg body weight.
arm group label: N8-GP
other name: NNC 0129-0000-1003
other name: N8-GP
criteria: 
gender: Male
minimum age: 0 Years
maximum age: 11 Years
healthy volunteers: No
last name: Global Clinical Registry (GCR, 1452)
role: Study Director
affiliation: Novo Nordisk A/S
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country: Brazil
country: Canada
country: France
country: Greece
country: Israel
country: Italy
country: Japan
country: Lithuania
country: Malaysia
country: Portugal
country: Puerto Rico
country: Switzerland
country: Turkey
country: Ukraine
country: United Kingdom
country: United States
country: Germany
url: http://novonordisk-trials.com
description: Clinical Trials at Novo Nordisk
citation: Tosetto A, Neff A, Lentz SR, Santagostino E, Nemes L, Sathar J, Meijer K, Chowdary P, Shen C, Landorph A, Hampton K. Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials. Haemophilia. 2020 May;26(3):450-458. doi: 10.1111/hae.13980. Epub 2020 Apr 15.
PMID: 32293786
citation: Saulyte Trakymiene S, Economou M, Kenet G, Landorph A, Shen C, Kearney S. Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5. J Thromb Haemost. 2020 Sep;18 Suppl 1(Suppl 1):15-25. doi: 10.1111/jth.15036.
PMID: 32940955
responsible party type: Sponsor
mesh term: Hemostatic Disorders
mesh term: Hemophilia A
mesh term: Blood Coagulation Disorders
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
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point of contact: 