<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/NCT01735175</url>
  </required_header>
  <id_info>
    <org_study_id>LA-EP06-301</org_study_id>
    <secondary_id>2011-004532-58</secondary_id>
    <nct_id>NCT01735175</nct_id>
  </id_info>
  <brief_title>Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®</brief_title>
  <acronym>PROTECT-1</acronym>
  <official_title>A Randomized, Double-blind, Parallel-group, Multi-center Phase 3 Comparative Study Investigating Efficacy and Safety of LA-EP2006 and Neulasta® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sandoz</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sandoz GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sandoz</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the&#xD;
      mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in&#xD;
      breast cancer patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized, double-blind trial compared the proposed biosimilar LA-EP2006 with the&#xD;
      reference Neulasta® in women (≥18 years) receiving chemotherapy for breast cancer. Therefore&#xD;
      patients were randomized to receive LA-EP2006 (n = 159) or the reference product (n = 157)&#xD;
      for ≤6 cycles of (neo)-adjuvant TAC (docetaxel 75mg/m^2, doxorubicin 50 mg/m^2, and&#xD;
      cyclophosphamide 500mg/m^2) chemotherapy. The primary end point was the duration of severe&#xD;
      neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute&#xD;
      neutrophil count &lt;0.5 × 10^9/l). The equivalence was confirmed if 95% CIs were within a ±1&#xD;
      day margin. LA-EP2006 was equivalent to the reference product in DSN (difference: 0.07 days;&#xD;
      95% CI [-0.12, 0.26]). Further, LA-EP2006 and the reference Neulasta® showed no clinically&#xD;
      meaningful differences regarding efficacy and safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">February 2014</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy</measure>
    <time_frame>21 days (Cycle 1 of chemotherapy treatment)</time_frame>
    <description>Mean duration of severe neutropenia, defined as number of consecutive days with ANC &lt;0.5 × 10^9 cells/L (grade 4 neutropenia).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Febrile Neutropenia (FN)</measure>
    <time_frame>across all cycles (18 weeks)</time_frame>
    <description>FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) &lt; 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN (&quot;febrile neutropenia&quot;, &quot;neutropenic sepsis&quot;) were taken into account.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles</measure>
    <time_frame>across al cycles (18 weeks)</time_frame>
    <description>Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of ANC Nadir in Cycle 1</measure>
    <time_frame>Cycle 1 (3 weeks)</time_frame>
    <description>The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With ANC Nadir Per Day in Cycle 1</measure>
    <time_frame>Cycle 1 (3 weeks)</time_frame>
    <description>Numbers of patients with ANC nadir based per day during Cycle 1 are given.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Recovery in Days in Cycle 1</measure>
    <time_frame>across Cycle 1 (3 weeks)</time_frame>
    <description>Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Infections by Cycle and Across All Cycles</measure>
    <time_frame>across all cycles (18 weeks)</time_frame>
    <description>The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class &quot;Infections and Infestations&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality Due to Infection</measure>
    <time_frame>Study course (41 weeks)</time_frame>
    <description>Number of patients with death due to infections</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">316</enrollment>
  <condition>Neutropenic Complications</condition>
  <condition>Breast Neoplasms</condition>
  <condition>Chemotherapy-induced Neutropenia</condition>
  <condition>Chemotherapeutic Toxicity</condition>
  <arm_group>
    <arm_group_label>Neulasta®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LA-EP2006</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LA-EP2006</intervention_name>
    <description>Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
    <arm_group_label>LA-EP2006</arm_group_label>
    <other_name>pegfilgrastim</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neulasta®</intervention_name>
    <description>Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
    <arm_group_label>Neulasta®</arm_group_label>
    <other_name>pegfilgrastim</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically proven breast cancer&#xD;
&#xD;
          -  eligible for six cycles of neoadjuvant or adjuvant chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  concurrent or prior chemotherapy for breast cancer&#xD;
&#xD;
          -  concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy,&#xD;
             immunotherapy, monoclonal antibodies, and/or biological therapy&#xD;
&#xD;
          -  concurrent prophylactic antibiotics&#xD;
&#xD;
          -  previous therapy with any G-CSF (granulocyte-colony stimulating factor) product&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandoz Biopharmaceutical Clinical Development</last_name>
    <role>Study Chair</role>
    <affiliation>Sandoz</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Ijui</city>
        <zip>98700-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Lajeado</city>
        <zip>95900-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Santo Andre</city>
        <zip>0960-650</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Andhra Pradesh</city>
        <zip>530002</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Delhi</city>
        <zip>110095</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Madurai</city>
        <zip>625107</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Maharashtra</city>
        <zip>411001</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Maharashtra</city>
        <zip>416008</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Maharashtra</city>
        <zip>440010</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Mumbai</city>
        <zip>422005</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Rajasthan</city>
        <zip>302013</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Aguascalientes</city>
        <zip>20230</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Juchitan</city>
        <zip>70000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>11461</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>23423</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Iasi</city>
        <zip>700106</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Suceava</city>
        <zip>720237</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Barnaul</city>
        <zip>656052</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Bashkortostan</city>
        <zip>450054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Berdsk</city>
        <zip>633004</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Ivanovo</city>
        <zip>153040</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Kabardino</city>
        <zip>361045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Kazan</city>
        <zip>420029</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Krasnodar</city>
        <zip>354057</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Kursk</city>
        <zip>305035</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Leningrad</city>
        <zip>188663</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Novgorod</city>
        <zip>173016</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Oktyabrskaya</city>
        <zip>355047</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Ryazan</city>
        <zip>390011</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>St. Petersburg</city>
        <zip>195067</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Tula</city>
        <zip>300053</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Cherkasy</city>
        <zip>18009</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Chernivtsi</city>
        <zip>58013</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Dnipropetrovsk</city>
        <zip>49102</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Kharkiv</city>
        <zip>61176</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Kriviy Rig</city>
        <zip>50048</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Lugansk</city>
        <zip>91000</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Mariupol</city>
        <zip>87500</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Vinnytsya</city>
        <zip>21029</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandoz Investigational Site</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69040</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>India</country>
    <country>Mexico</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Ukraine</country>
  </location_countries>
  <results_reference>
    <citation>Harbeck N, Lipatov O, Frolova M, Udovitsa D, Topuzov E, Ganea-Motan DE, Nakov R, Singh P, Rudy A, Blackwell K. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol. 2016 Jun;12(11):1359-67. doi: 10.2217/fon-2016-0016. Epub 2016 Mar 29.</citation>
    <PMID>27020170</PMID>
  </results_reference>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>November 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <results_first_submitted>March 28, 2017</results_first_submitted>
  <results_first_submitted_qc>March 28, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 15, 2017</results_first_posted>
  <last_update_submitted>June 29, 2017</last_update_submitted>
  <last_update_submitted_qc>June 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>biosimilars</keyword>
  <keyword>Pegfilgrastim,</keyword>
  <keyword>G-CSF,</keyword>
  <keyword>neutropenia,</keyword>
  <keyword>breast cancer,</keyword>
  <keyword>myelosuppressive chemotherapy,</keyword>
  <keyword>supportive care</keyword>
  <keyword>granulocyte-colony-stimulating factor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Neutropenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>LA-EP2006</title>
          <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
        </group>
        <group group_id="P2">
          <title>Neulasta®</title>
          <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="159"/>
                <participants group_id="P2" count="157"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed All Cycles</title>
              <participants_list>
                <participants group_id="P1" count="141"/>
                <participants group_id="P2" count="150"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed All Treatments as Planned</title>
              <participants_list>
                <participants group_id="P1" count="140"/>
                <participants group_id="P2" count="150"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed the 6-month SFU Visit</title>
              <participants_list>
                <participants group_id="P1" count="120"/>
                <participants group_id="P2" count="138"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="130"/>
                <participants group_id="P2" count="144"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other (mostly EOS/EOT visit missing)</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>LA-EP2006</title>
          <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
        </group>
        <group group_id="B2">
          <title>Neulasta®</title>
          <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</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="159"/>
            <count group_id="B2" value="157"/>
            <count group_id="B3" value="316"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.9" spread="9.53"/>
                    <measurement group_id="B2" value="50.5" spread="10.87"/>
                    <measurement group_id="B3" value="50.2" spread="10.20"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="159"/>
                    <measurement group_id="B2" value="157"/>
                    <measurement group_id="B3" value="316"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="148"/>
                    <measurement group_id="B2" value="139"/>
                    <measurement group_id="B3" value="287"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>More than one race patients (n = 6) were of Mestizo or Parda origin.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="129"/>
                    <measurement group_id="B2" value="127"/>
                    <measurement group_id="B3" value="256"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <population>BMI is missing for 1 patient allocated to Neulasta®</population>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="156"/>
                    <count group_id="B3" value="315"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.47" spread="26.76"/>
                    <measurement group_id="B2" value="27.44" spread="26.35"/>
                    <measurement group_id="B3" value="27.45" spread="26.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time since diagnosis</title>
          <description>For 4 patients in the LA-EP2006 treatment group, time since initial diagnosis was &gt; 12 months. It was confirmed by the respective study site that the patients had not received treatment between diagnosis and study entry.</description>
          <population>For 6 patients in the LA-EP2006 treatment group and 10 patients in the Neulasta® treatment group, the date of initial diagnosis was incomplete.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="153"/>
                    <count group_id="B2" value="147"/>
                    <count group_id="B3" value="300"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.35" lower_limit="0.1" upper_limit="76.0"/>
                    <measurement group_id="B2" value="1.38" lower_limit="0.2" upper_limit="10.9"/>
                    <measurement group_id="B3" value="1.38" lower_limit="0.1" upper_limit="76.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease stage</title>
          <description>TNM Disease stage was defined according to the American Joint Committee on Cancer (AJCC): (I) = T1 N0 M0 / T0 N1mi M0 / T1 N1mi M0; (II) = T0 N1 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0 / T3 N0 M0; (III) = T0 N2 M0 / T1 N2 M0 / T2 N2 M0 / T3 N1 M0 / T3 N2 M0 / T4 N0 M0 / T4 N1 M0 / T4 N2 M0 / AnyT N3 M0; (IV) = AnyT AnyN M1; T: size or direct extent of the primary tumour; N: degree of spread to regional lymph nodes; N1mi: Micrometastases (&gt; 0.2 mm and/or &gt; 200 cells, but none &gt; 2.0 mm); M: presence of distant; https://www.cancer.gov/types/breast/hp/breast-treatment-pdq#link/_27</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>I</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>II</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74"/>
                    <measurement group_id="B2" value="73"/>
                    <measurement group_id="B3" value="147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>III</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IV</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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>
          <title>Previous breast cancer surgery</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="149"/>
                    <measurement group_id="B2" value="146"/>
                    <measurement group_id="B3" value="295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Previous radiotherapy</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ECOG performance status</title>
          <description>ECOG = Eastern Cooperative Oncology Group</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>0 (fully active)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="128"/>
                    <measurement group_id="B2" value="123"/>
                    <measurement group_id="B3" value="251"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 (restricted in physically strenuous activity)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="159"/>
                    <count group_id="B2" value="157"/>
                    <count group_id="B3" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy</title>
        <description>Mean duration of severe neutropenia, defined as number of consecutive days with ANC &lt;0.5 × 10^9 cells/L (grade 4 neutropenia).</description>
        <time_frame>21 days (Cycle 1 of chemotherapy treatment)</time_frame>
        <population>FAS set = full analysis set; PP set = per protocol set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy</title>
          <description>Mean duration of severe neutropenia, defined as number of consecutive days with ANC &lt;0.5 × 10^9 cells/L (grade 4 neutropenia).</description>
          <population>FAS set = full analysis set; PP set = per protocol set</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="159"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FAS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="155"/>
                    <count group_id="O2" value="155"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75" spread="0.878"/>
                    <measurement group_id="O2" value="0.83" spread="0.898"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PP</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="146"/>
                    <count group_id="O2" value="149"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75" spread="0.875"/>
                    <measurement group_id="O2" value="0.79" spread="0.872"/>
                  </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>The hierarchical test procedure aimed to show that&#xD;
LA-EP2006 and Neulasta® are equivalent with respect to DSN duration in Cycle 1 (margin±1 day), and, if so&#xD;
LA-EP2006 is non-inferior to Neulasta® with respect to DSN duration in Cycle 1 (margin of -0.6 days).</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta® was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.</non_inferiority_desc>
            <p_value>0.05</p_value>
            <method>ANCOVA</method>
            <method_desc>The primary endpoints was analyzed with analysis of covariance (ANCOVA).</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.12</ci_lower_limit>
            <ci_upper_limit>0.26</ci_upper_limit>
            <estimate_desc>The difference between LA-EP2006 and reference pegfilgrastim was 0.07 days (95% CI [-0.12, 0.26]). 95% CIs were within the predefined margin of ±1 day confirming equivalence.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The hierarchical test procedure aimed to show that&#xD;
LA-EP2006 and Neulasta® are equivalent with respect to DSN duration in Cycle 1 (margin±1 day), and, if so&#xD;
LA-EP2006 is non-inferior to Neulasta® with respect to DSN duration in Cycle 1 (margin of -0.6 days).</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.</non_inferiority_desc>
            <p_value>0.05</p_value>
            <method>ANCOVA</method>
            <method_desc>The primary endpoints was analyzed with analysis of covariance (ANCOVA).</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.12</ci_lower_limit>
            <ci_upper_limit>0.26</ci_upper_limit>
            <estimate_desc>LA-EP2006 is non-inferior to Neulasta® because the lower bound of the 95% CI is entirely above the non-inferiority margin of -0.6 days.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Febrile Neutropenia (FN)</title>
        <description>FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) &lt; 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN (&quot;febrile neutropenia&quot;, &quot;neutropenic sepsis&quot;) were taken into account.</description>
        <time_frame>across all cycles (18 weeks)</time_frame>
        <population>Number of patients with at least one episode of febrile neutropenia by cycle and across all cycles (FAS set)</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Febrile Neutropenia (FN)</title>
          <description>FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) &lt; 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN (&quot;febrile neutropenia&quot;, &quot;neutropenic sepsis&quot;) were taken into account.</description>
          <population>Number of patients with at least one episode of febrile neutropenia by cycle and across all cycles (FAS set)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="159"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>All cycles (at least on incidence)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles</title>
        <description>Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.</description>
        <time_frame>across al cycles (18 weeks)</time_frame>
        <population>Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles</title>
          <description>Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.</description>
          <population>Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="159"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depth of ANC Nadir in Cycle 1</title>
        <description>The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.</description>
        <time_frame>Cycle 1 (3 weeks)</time_frame>
        <population>FAS set = full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Depth of ANC Nadir in Cycle 1</title>
          <description>The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.</description>
          <population>FAS set = full analysis set</population>
          <units>10^9 cells/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
                <count group_id="O2" value="155"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.102" spread="1.5398"/>
                    <measurement group_id="O2" value="0.921" spread="1.1771"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With ANC Nadir Per Day in Cycle 1</title>
        <description>Numbers of patients with ANC nadir based per day during Cycle 1 are given.</description>
        <time_frame>Cycle 1 (3 weeks)</time_frame>
        <population>FAS set = full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With ANC Nadir Per Day in Cycle 1</title>
          <description>Numbers of patients with ANC nadir based per day during Cycle 1 are given.</description>
          <population>FAS set = full analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="159"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Days 1-5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101"/>
                    <measurement group_id="O2" value="104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Days 10-15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Recovery in Days in Cycle 1</title>
        <description>Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given.</description>
        <time_frame>across Cycle 1 (3 weeks)</time_frame>
        <population>FAS set = full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Recovery in Days in Cycle 1</title>
          <description>Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given.</description>
          <population>FAS set = full analysis set</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="154"/>
                <count group_id="O2" value="154"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.58" spread="1.053"/>
                    <measurement group_id="O2" value="1.72" spread="1.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Infections by Cycle and Across All Cycles</title>
        <description>The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class &quot;Infections and Infestations&quot;.</description>
        <time_frame>across all cycles (18 weeks)</time_frame>
        <population>Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Infections by Cycle and Across All Cycles</title>
          <description>The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class &quot;Infections and Infestations&quot;.</description>
          <population>Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="159"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mortality Due to Infection</title>
        <description>Number of patients with death due to infections</description>
        <time_frame>Study course (41 weeks)</time_frame>
        <population>FAS set = full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>LA-EP2006</title>
            <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
          <group group_id="O2">
            <title>Neulasta®</title>
            <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
          </group>
        </group_list>
        <measure>
          <title>Mortality Due to Infection</title>
          <description>Number of patients with death due to infections</description>
          <population>FAS set = full analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="159"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="159"/>
                    <measurement group_id="O2" value="155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients were followed for a 6-month safety period from the last administration of pegfilgrastim.</time_frame>
      <desc>If not otherwise specified, only treatment-emergent adverse event (TEAEs) (i.e. AEs with a date of onset on or after the date of the first administration of chemotherapy and not later than 30 days after the last dose of chemotherapy) and post-TEAEs (i.e. AEs with a date of onset after the time point of 30 days after the last chemotherapy administration) are reported. SAF set = safety analysis set was used</desc>
      <group_list>
        <group group_id="E1">
          <title>LA-EP2006</title>
          <description>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.&#xD;
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
        </group>
        <group group_id="E2">
          <title>Neulasta®</title>
          <description>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.&#xD;
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.</description>
        </group>
      </group_list>
      <serious_events>
        <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="4" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium febrile</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Venous thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <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="140" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="128" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="64" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="58" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Vomitting</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Diarrhoe</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="56" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Odema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning and procedural complications</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Aspatate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="82" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular disorders</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="157"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Strategic Planning, Biopharmaceutical Clinical Development</name_or_title>
      <organization>Sandoz</organization>
      <phone>+49 (0) 8024 476 - 0</phone>
      <email>biopharma.clinicaltrials@sandoz.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/NCT01735175
org study id: LA-EP06-301
secondary id: 2011-004532-58
nct id: NCT01735175
lead sponsor: 
collaborator: 
has dmc: Yes
The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the
      mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in
      breast cancer patients.
This randomized, double-blind trial compared the proposed biosimilar LA-EP2006 with the
      reference Neulasta® in women (≥18 years) receiving chemotherapy for breast cancer. Therefore
      patients were randomized to receive LA-EP2006 (n = 159) or the reference product (n = 157)
      for ≤6 cycles of (neo)-adjuvant TAC (docetaxel 75mg/m^2, doxorubicin 50 mg/m^2, and
      cyclophosphamide 500mg/m^2) chemotherapy. The primary end point was the duration of severe
      neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute
      neutrophil count <0.5 × 10^9/l). The equivalence was confirmed if 95% CIs were within a ±1
      day margin. LA-EP2006 was equivalent to the reference product in DSN (difference: 0.07 days;
      95% CI [-0.12, 0.26]). Further, LA-EP2006 and the reference Neulasta® showed no clinically
      meaningful differences regarding efficacy and safety.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy
time frame: 21 days (Cycle 1 of chemotherapy treatment)
description: Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9 cells/L (grade 4 neutropenia).
measure: Incidence of Febrile Neutropenia (FN)
time frame: across all cycles (18 weeks)
description: FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.
measure: Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
time frame: across al cycles (18 weeks)
description: Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.
measure: Depth of ANC Nadir in Cycle 1
time frame: Cycle 1 (3 weeks)
description: The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.
measure: Number of Patients With ANC Nadir Per Day in Cycle 1
time frame: Cycle 1 (3 weeks)
description: Numbers of patients with ANC nadir based per day during Cycle 1 are given.
measure: Time to ANC Recovery in Days in Cycle 1
time frame: across Cycle 1 (3 weeks)
description: Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given.
measure: Frequency of Infections by Cycle and Across All Cycles
time frame: across all cycles (18 weeks)
description: The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".
measure: Mortality Due to Infection
time frame: Study course (41 weeks)
description: Number of patients with death due to infections
arm group label: Neulasta®
arm group type: Active Comparator
description: During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.
arm group label: LA-EP2006
arm group type: Experimental
description: During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.
intervention type: Drug
intervention name: LA-EP2006
description: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
arm group label: LA-EP2006
other name: pegfilgrastim
intervention type: Drug
intervention name: Neulasta®
description: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
arm group label: Neulasta®
other name: pegfilgrastim
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sandoz Biopharmaceutical Clinical Development
role: Study Chair
affiliation: Sandoz
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country: Brazil
country: India
country: Mexico
country: Romania
country: Russian Federation
country: Ukraine
citation: Harbeck N, Lipatov O, Frolova M, Udovitsa D, Topuzov E, Ganea-Motan DE, Nakov R, Singh P, Rudy A, Blackwell K. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol. 2016 Jun;12(11):1359-67. doi: 10.2217/fon-2016-0016. Epub 2016 Mar 29.
PMID: 27020170
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Neutropenia
sharing ipd: Undecided
participant flow: 
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point of contact: 