<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/NCT01724866</url>
  </required_header>
  <id_info>
    <org_study_id>SPI-GCF-12-201</org_study_id>
    <secondary_id>2013-003094-10</secondary_id>
    <nct_id>NCT01724866</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of SPI-2012 or Pegfilgrastim for the Management of Neutropenia in Participants With Breast Cancer</brief_title>
  <official_title>Phase 2, Open-Label, Dose-Ranging Study of SPI-2012 (HM10460A) or Pegfilgrastim Use for the Management of Neutropenia in Patients With Breast Cancer Who Are Candidates for Adjuvant and Neoadjuvant Chemotherapy With the Docetaxel + Cyclophosphamide (TC) Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spectrum Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spectrum Pharmaceuticals, Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effect of test doses of SPI-2012 on the duration&#xD;
      of severe neutropenia (DSN) during Cycle 1 in participants with breast cancer who are&#xD;
      candidates for adjuvant or neoadjuvant chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label, multicenter, dose ranging study, sequentially enrolled by study dose,&#xD;
      with a non-inferiority design to compare the effectiveness of SPI-2012 relative to a fixed&#xD;
      dose of pegfilgrastim as a concurrent active control to each dose of SPI-2012 in participants&#xD;
      with breast cancer. This study included four arms comprising three dose levels of SPI-2012&#xD;
      (Arm 1: 45 µg/kg, Arm 2: 135 µg/kg, Arm 3: 270 µg/kg) versus pegfilgrastim (Arm 4: 6 mg). The&#xD;
      start of study is defined as the initiation of treatment with SPI-2012 or pegfilgrastim. The&#xD;
      duration of treatment consists of a maximum of 4 cycles (21 days per cycle) beginning on Day&#xD;
      1 with chemotherapy administration and continue through Day 21, plus a 30-day follow-up&#xD;
      period, unless any of the discontinuation criteria applies.&#xD;
&#xD;
      The target population are participants with breast cancer who are candidates for neoadjuvant&#xD;
      or adjuvant treatment with Docetaxel + Cyclophosphamide (TC) chemotherapy. All participants&#xD;
      who receive at least 1 dose of either SPI-2012 or pegfilgrastim were followed for safety&#xD;
      through 30 days after their last dose of study treatment or until all treatment-related&#xD;
      adverse events (AEs) have resolved or returned to baseline/Grade 1, whichever is longer, or&#xD;
      until it is determined that the outcome will not change with further follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 25, 2013</start_date>
  <completion_date type="Actual">August 12, 2014</completion_date>
  <primary_completion_date type="Actual">August 12, 2014</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of Severe Neutropenia (DSN) in Cycle 1</measure>
    <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
    <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of DSN in Cycle 2</measure>
    <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
    <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of DSN in Cycle 3</measure>
    <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
    <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of DSN in Cycle 4</measure>
    <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
    <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Recovery in Cycle 1</measure>
    <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
    <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥ 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Recovery in Cycle 2</measure>
    <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
    <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Recovery in Cycle 3</measure>
    <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
    <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Recovery in Cycle 4</measure>
    <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
    <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1</measure>
    <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
    <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute ANC Nadir Overtime in Cycle 2</measure>
    <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
    <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute ANC Nadir Overtime in Cycle 3</measure>
    <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
    <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute ANC Nadir Overtime in Cycle 4</measure>
    <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
    <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of ANC Nadir in Cycle 1</measure>
    <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
    <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of ANC Nadir in Cycle 2</measure>
    <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
    <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of ANC Nadir in Cycle 3</measure>
    <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
    <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of ANC Nadir in Cycle 4</measure>
    <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
    <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Nadir in Cycle 1</measure>
    <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
    <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Nadir in Cycle 2</measure>
    <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
    <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Nadir in Cycle 3</measure>
    <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
    <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ANC Nadir in Cycle 4</measure>
    <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
    <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4</measure>
    <time_frame>Cycle 1 to Cycle 4 (each cycle was 21 days)</time_frame>
    <description>FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities</measure>
    <time_frame>From the first dose up to 30 days post last dose of study drug (up to 4 months)</time_frame>
    <description>An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities (&quot;Hematology and Chemistry&quot;) were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4</measure>
    <time_frame>All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Positive Antibodies for SPI-2012</measure>
    <time_frame>Up to the end of the study (Approximately 3.5 months)</time_frame>
    <description>Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Concentration of SPI-2012 (Tmax)</measure>
    <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
    <description>Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration of SPI-2012 (Cmax)</measure>
    <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
    <description>Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)</measure>
    <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
    <description>AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of SPI-2012 (t1/2)</measure>
    <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
    <description>t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">148</enrollment>
  <condition>Neutropenia</condition>
  <arm_group>
    <arm_group_label>Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Pegfilgrastim 6 milligram (mg), SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPI-2012</intervention_name>
    <description>SPI-2012 SC injection.</description>
    <arm_group_label>Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <other_name>Rolontis®</other_name>
    <other_name>HM10460A</other_name>
    <other_name>Eflapegrastim</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegfilgrastim</intervention_name>
    <description>Pegfilgrastim SC injection, per manufacturer's Prescribing Information.</description>
    <arm_group_label>Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <other_name>Neulasta®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel given based on standard dose for chemotherapy.</description>
    <arm_group_label>Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide given based on standard dose for chemotherapy.</description>
    <arm_group_label>Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <arm_group_label>Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed breast cancer and candidate for adjuvant or neoadjuvant&#xD;
             chemotherapy&#xD;
&#xD;
          -  Candidate for docetaxel and cyclophosphamide chemotherapy&#xD;
&#xD;
          -  Female or male at least 18 years of age&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) ≤ 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1.5×109/L&#xD;
&#xD;
          -  Platelet count ≥ 100 x 10^9/L&#xD;
&#xD;
          -  Creatinine ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin ≤1.5 mg/dL(≤ 25.65 μmol/L).&#xD;
&#xD;
          -  Aspartate aminotransferase per serum glutamic-oxaloacetic transaminase (AST/SGOT)&#xD;
             and/or alanine aminotransferase per serum glutamic-pyruvic transaminase (ALT/SGPT) ≤&#xD;
             2.5 x ULN&#xD;
&#xD;
          -  Hemoglobin &gt; 9 g/dL&#xD;
&#xD;
          -  Alkaline phosphatase ≤ 1.5 x ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known sensitivity to E. coli-derived products or known sensitivity to any of the&#xD;
             products to be administered&#xD;
&#xD;
          -  Known Human Immunodeficiency Virus (HIV) infection&#xD;
&#xD;
          -  Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) diagnosis with detectable viral&#xD;
             load or immunological evidence of chronic active disease&#xD;
&#xD;
          -  Active infection or any serious underlying medical condition that would impair ability&#xD;
             to receive protocol treatment&#xD;
&#xD;
          -  Prior bone marrow or stem cell transplant&#xD;
&#xD;
          -  Prolonged exposure to glucocorticosteroids and immunosuppressive agents&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arizona Center for Cancer Care</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Desert Springs Cancer Care</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85255</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Cancer Associates for Research and Excellence</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaver Medical Group</name>
      <address>
        <city>Highland</city>
        <state>California</state>
        <zip>92346</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Cancer Associates for Research and Excellence</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>92025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kentucky Cancer Clinic</name>
      <address>
        <city>Hazard</city>
        <state>Kentucky</state>
        <zip>41701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology, PC</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore Hematology/Oncology Associates</name>
      <address>
        <city>Setauket</city>
        <state>New York</state>
        <zip>11733</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Good Samaritan Hospital, Corvallis</name>
      <address>
        <city>Corvallis</city>
        <state>Oregon</state>
        <zip>97330</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frankston Hospital</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hobart</name>
      <address>
        <city>Brisbane</city>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ashford Cancer Center Research</name>
      <address>
        <city>Kurralta Park</city>
        <zip>5037</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Breast Cancer Research Center, WA</name>
      <address>
        <city>Perth</city>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ballarat Oncology &amp; Haematology</name>
      <address>
        <city>Wendouree</city>
        <zip>3355</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LTD &quot; Cancer Center of Adjara Autonomic Republic&quot;</name>
      <address>
        <city>Batumi</city>
        <zip>6000</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ltd ' Medulla - Chemotherapy and Immunotherapy Clinic</name>
      <address>
        <city>Tbilisi</city>
        <zip>0186</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Health Center</name>
      <address>
        <city>Budapest</city>
        <zip>1062</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institute of Oncology</name>
      <address>
        <city>Budapest</city>
        <zip>1122</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uzsoki Hospital</name>
      <address>
        <city>Budapest</city>
        <zip>1146</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Debrecen, Oncology Clinic</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szabolcs - Szatmár - Bereg megyei Kórházak és Egyetemi Oktatókórház</name>
      <address>
        <city>Nyíregyháza</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziv Medical Center</name>
      <address>
        <city>Zefat</city>
        <zip>13100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regionalny Szpital Specjalistyczny</name>
      <address>
        <city>Grudziądz</city>
        <zip>86-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki w Krakowie</name>
      <address>
        <city>Kraków</city>
        <zip>31-501</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dzienny Oddział Chemioterapii</name>
      <address>
        <city>Racibórz</city>
        <zip>47-400</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MTZ Clinical Research Sp. z o.o.</name>
      <address>
        <city>Warszawa</city>
        <zip>02-106</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Georgia</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Poland</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
    <country>Czech Republic</country>
    <country>Czechia</country>
  </removed_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <results_first_submitted>February 7, 2022</results_first_submitted>
  <results_first_submitted_qc>March 22, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 15, 2022</results_first_posted>
  <disposition_first_submitted>January 23, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>January 23, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 5, 2020</disposition_first_posted>
  <last_update_submitted>March 22, 2022</last_update_submitted>
  <last_update_submitted_qc>March 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neutropenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 27 investigative sites in the United States (10 sites), Australia (5 sites), Georgia (2 sites), Hungary (5 sites), Israel (1 site), and Poland (4 sites) from 25 March 2013 to 12 August 2014.</recruitment_details>
      <pre_assignment_details>A total of 148 participants were randomized in the study, out of which 138 participants completed the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)</title>
          <description>Participants received SPI-2012 45 µg/kg, subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="P2">
          <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
          <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="P3">
          <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
          <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="P4">
          <title>Arm 4: Pegfilgrastim and TC</title>
          <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="37"/>
                <participants group_id="P3" count="36"/>
                <participants group_id="P4" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Evaluable Population</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="36"/>
                <participants group_id="P3" count="36"/>
                <participants group_id="P4" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="33"/>
                <participants group_id="P4" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Initiation of Non-Protocol Therapy Either for Progressive Disease or Intolerance of TC Regimen</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator's Discretion</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Need for Chemotherapy or Chemotherapy Regimen was Changed due to Amended HER2 Status</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant Refused Further Treatment or Withdrew Consent</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
      <group_list>
        <group group_id="B1">
          <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
          <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="B2">
          <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
          <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="B3">
          <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
          <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="B4">
          <title>Arm 4: Pegfilgrastim and TC</title>
          <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="B5">
          <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="39"/>
            <count group_id="B2" value="36"/>
            <count group_id="B3" value="36"/>
            <count group_id="B4" value="36"/>
            <count group_id="B5" value="147"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.8" spread="11.31"/>
                    <measurement group_id="B2" value="56.8" spread="10.63"/>
                    <measurement group_id="B3" value="55.7" spread="9.79"/>
                    <measurement group_id="B4" value="60.4" spread="10.43"/>
                    <measurement group_id="B5" value="58.2" spread="10.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="36"/>
                    <measurement group_id="B5" value="144"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="133"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Others</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Duration of Severe Neutropenia (DSN) in Cycle 1</title>
        <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 1.</description>
        <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Severe Neutropenia (DSN) in Cycle 1</title>
          <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 1.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</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="39"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.03" spread="1.547"/>
                    <measurement group_id="O2" value="0.44" spread="1.275"/>
                    <measurement group_id="O3" value="0.03" spread="0.167"/>
                    <measurement group_id="O4" value="0.31" spread="0.822"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% confidence interval (CI) for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>0.296</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.72</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.19</ci_lower_limit>
            <ci_upper_limit>1.27</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>0.002</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.14</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.28</ci_lower_limit>
            <ci_upper_limit>0.64</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-values was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.28</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.56</ci_lower_limit>
            <ci_upper_limit>-0.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of DSN in Cycle 2</title>
        <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 2.</description>
        <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of DSN in Cycle 2</title>
          <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 2.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</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="39"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="1.022"/>
                    <measurement group_id="O2" value="0.12" spread="0.478"/>
                    <measurement group_id="O3" value="0.03" spread="0.171"/>
                    <measurement group_id="O4" value="0.08" spread="0.368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.38</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.06</ci_lower_limit>
            <ci_upper_limit>0.74</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.04</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.16</ci_lower_limit>
            <ci_upper_limit>0.24</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.19</ci_lower_limit>
            <ci_upper_limit>0.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of DSN in Cycle 3</title>
        <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 3.</description>
        <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of DSN in Cycle 3</title>
          <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 3.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</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="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.45" spread="1.132"/>
                    <measurement group_id="O2" value="0.16" spread="0.628"/>
                    <measurement group_id="O3" value="0.15" spread="0.610"/>
                    <measurement group_id="O4" value="0.14" spread="0.593"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>0.002</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.31</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.07</ci_lower_limit>
            <ci_upper_limit>0.72</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.27</ci_lower_limit>
            <ci_upper_limit>0.30</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.27</ci_lower_limit>
            <ci_upper_limit>0.28</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of DSN in Cycle 4</title>
        <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 4.</description>
        <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of DSN in Cycle 4</title>
          <description>DSN was defined as the interval from the day of first observation of severe neutropenia (ANC &lt;0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to =&gt; 2.0*10^9/L in Cycle 4.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</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="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="33"/>
                <count group_id="O4" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="4.579"/>
                    <measurement group_id="O2" value="0.19" spread="0.738"/>
                    <measurement group_id="O3" value="0.09" spread="0.522"/>
                    <measurement group_id="O4" value="0.11" spread="0.404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>0.781</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.94</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.01</ci_lower_limit>
            <ci_upper_limit>2.47</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.17</ci_lower_limit>
            <ci_upper_limit>0.38</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A 2-sided 95% CI for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the upper CI was &lt; 1 day.</non_inferiority_desc>
            <p_value>&lt;0.001</p_value>
            <method>Bootstrap method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.23</ci_lower_limit>
            <ci_upper_limit>0.22</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Recovery in Cycle 1</title>
        <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥ 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1.</description>
        <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Recovery in Cycle 1</title>
          <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥ 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 1.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0" lower_limit="10.0" upper_limit="11.0"/>
                    <measurement group_id="O2" value="8.5" lower_limit="8.0" upper_limit="9.0"/>
                    <measurement group_id="O3" value="8.0" lower_limit="7.0" upper_limit="9.0"/>
                    <measurement group_id="O4" value="9.0" lower_limit="8.0" upper_limit="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.1</ci_lower_limit>
            <ci_upper_limit>1.8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.711</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>1.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.028</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Recovery in Cycle 2</title>
        <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2.</description>
        <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Recovery in Cycle 2</title>
          <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 2.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" lower_limit="10.0" upper_limit="11.0"/>
                    <measurement group_id="O2" value="9.5" lower_limit="8.0" upper_limit="10.0"/>
                    <measurement group_id="O3" value="10.0" lower_limit="8.0" upper_limit="14.0"/>
                    <measurement group_id="O4" value="10.0" lower_limit="8.0" upper_limit="11.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.672</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.8</ci_lower_limit>
            <ci_upper_limit>1.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.348</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.973</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4</ci_lower_limit>
            <ci_upper_limit>2.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Recovery in Cycle 3</title>
        <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3.</description>
        <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 3.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Recovery in Cycle 3</title>
          <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 3.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0" lower_limit="10.0" upper_limit="11.0"/>
                    <measurement group_id="O2" value="9.5" lower_limit="8.0" upper_limit="12.0"/>
                    <measurement group_id="O3" value="9.0" lower_limit="8.0" upper_limit="13.0"/>
                    <measurement group_id="O4" value="10.0" lower_limit="9.0" upper_limit="11.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.618</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.8</ci_lower_limit>
            <ci_upper_limit>1.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.661</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.754</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.3</ci_lower_limit>
            <ci_upper_limit>2.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Recovery in Cycle 4</title>
        <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4.</description>
        <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 4.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Recovery in Cycle 4</title>
          <description>Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants with recovery in Cycle 4.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" lower_limit="10.0" upper_limit="13.0"/>
                    <measurement group_id="O2" value="10.0" lower_limit="9.0" upper_limit="11.0"/>
                    <measurement group_id="O3" value="10.0" lower_limit="8.0" upper_limit="14.0"/>
                    <measurement group_id="O4" value="10.0" lower_limit="8.0" upper_limit="11.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.009</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.1</ci_lower_limit>
            <ci_upper_limit>1.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.527</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.7</ci_lower_limit>
            <ci_upper_limit>1.8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A Cox proportional hazards model was used to estimate the hazard ratio and its two-sided 95% CI.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.815</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4</ci_lower_limit>
            <ci_upper_limit>3.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1</title>
        <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.</description>
        <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1</title>
          <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
          <units>10^9 ANC per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.77"/>
                    <measurement group_id="O2" value="4.0" spread="3.86"/>
                    <measurement group_id="O3" value="7.2" spread="5.47"/>
                    <measurement group_id="O4" value="3.2" spread="2.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.008</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.911</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute ANC Nadir Overtime in Cycle 2</title>
        <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.</description>
        <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute ANC Nadir Overtime in Cycle 2</title>
          <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>10^9 ANC/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="39"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="1.89"/>
                    <measurement group_id="O2" value="3.9" spread="2.55"/>
                    <measurement group_id="O3" value="6.8" spread="6.30"/>
                    <measurement group_id="O4" value="3.3" spread="2.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.633</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.027</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute ANC Nadir Overtime in Cycle 3</title>
        <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.</description>
        <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute ANC Nadir Overtime in Cycle 3</title>
          <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>10^9 ANC/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="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="1.87"/>
                    <measurement group_id="O2" value="4.4" spread="3.26"/>
                    <measurement group_id="O3" value="6.1" spread="4.81"/>
                    <measurement group_id="O4" value="3.5" spread="1.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.015</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.571</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.066</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute ANC Nadir Overtime in Cycle 4</title>
        <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.</description>
        <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute ANC Nadir Overtime in Cycle 4</title>
          <description>Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>10^9 ANC/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="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="33"/>
                <count group_id="O4" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="2.12"/>
                    <measurement group_id="O2" value="4.1" spread="2.86"/>
                    <measurement group_id="O3" value="4.8" spread="3.00"/>
                    <measurement group_id="O4" value="2.7" spread="1.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.106</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.156</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Asymptotic Normality Assumption</method>
            <method_desc>P-values was obtained based upon asymptotic normality assumption on the log10 transformed data.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depth of ANC Nadir in Cycle 1</title>
        <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.</description>
        <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Depth of ANC Nadir in Cycle 1</title>
          <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
          <units>10^9 ANC/L</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" lower_limit="0.0" upper_limit="9.0"/>
                    <measurement group_id="O2" value="3.0" lower_limit="0.1" upper_limit="14.1"/>
                    <measurement group_id="O3" value="6.2" lower_limit="0.2" upper_limit="21.0"/>
                    <measurement group_id="O4" value="3.0" lower_limit="0.0" upper_limit="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.25</ci_lower_limit>
            <ci_upper_limit>0.80</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.53</ci_lower_limit>
            <ci_upper_limit>2.04</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>2.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.40</ci_lower_limit>
            <ci_upper_limit>4.54</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depth of ANC Nadir in Cycle 2</title>
        <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.</description>
        <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Depth of ANC Nadir in Cycle 2</title>
          <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>10^9 ANC/L</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" lower_limit="0.1" upper_limit="8.0"/>
                    <measurement group_id="O2" value="3.3" lower_limit="0.1" upper_limit="9.5"/>
                    <measurement group_id="O3" value="4.8" lower_limit="0.3" upper_limit="25.7"/>
                    <measurement group_id="O4" value="2.9" lower_limit="0.1" upper_limit="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.30</ci_lower_limit>
            <ci_upper_limit>0.80</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.70</ci_lower_limit>
            <ci_upper_limit>1.79</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.07</ci_lower_limit>
            <ci_upper_limit>2.79</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depth of ANC Nadir in Cycle 3</title>
        <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.</description>
        <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Depth of ANC Nadir in Cycle 3</title>
          <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>10^9 ANC/L</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" lower_limit="0.0" upper_limit="7.3"/>
                    <measurement group_id="O2" value="3.4" lower_limit="0.1" upper_limit="12.3"/>
                    <measurement group_id="O3" value="4.1" lower_limit="0.2" upper_limit="21.4"/>
                    <measurement group_id="O4" value="3.5" lower_limit="0.1" upper_limit="8.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.34</ci_lower_limit>
            <ci_upper_limit>0.89</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>1.85</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.97</ci_lower_limit>
            <ci_upper_limit>2.49</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depth of ANC Nadir in Cycle 4</title>
        <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.</description>
        <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Depth of ANC Nadir in Cycle 4</title>
          <description>Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>10^9 ANC/L</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="33"/>
                <count group_id="O4" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="0.0" upper_limit="9.2"/>
                    <measurement group_id="O2" value="4.2" lower_limit="0.1" upper_limit="11.2"/>
                    <measurement group_id="O3" value="4.2" lower_limit="0.4" upper_limit="11.9"/>
                    <measurement group_id="O4" value="2.4" lower_limit="0.1" upper_limit="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>0.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.40</ci_lower_limit>
            <ci_upper_limit>1.10</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.87</ci_lower_limit>
            <ci_upper_limit>2.38</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>1.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.23</ci_lower_limit>
            <ci_upper_limit>2.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Nadir in Cycle 1</title>
        <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
        <time_frame>Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Nadir in Cycle 1</title>
          <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="7.0" upper_limit="8.0"/>
                    <measurement group_id="O2" value="7.0" lower_limit="7.0" upper_limit="NA">The upper limit of Kaplan-Meier 95% confidence interval was not estimable due to too many events at median value.</measurement>
                    <measurement group_id="O3" value="7.0" lower_limit="7.0" upper_limit="8.0"/>
                    <measurement group_id="O4" value="7.5" lower_limit="7.0" upper_limit="16.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Nadir in Cycle 2</title>
        <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
        <time_frame>Cycle 2 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Nadir in Cycle 2</title>
          <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="8.0" upper_limit="NA">The upper limit of Kaplan-Meier 95% confidence interval was not estimable due to too many events at median value.</measurement>
                    <measurement group_id="O2" value="7.0" lower_limit="7.0" upper_limit="8.0"/>
                    <measurement group_id="O3" value="8.0" lower_limit="7.0" upper_limit="10.0"/>
                    <measurement group_id="O4" value="8.0" lower_limit="7.0" upper_limit="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Nadir in Cycle 3</title>
        <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
        <time_frame>Cycle 3 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Nadir in Cycle 3</title>
          <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="8.0" upper_limit="NA">The upper limit of Kaplan-Meier 95% confidence interval was not estimable due to too many events at median value.</measurement>
                    <measurement group_id="O2" value="7.0" lower_limit="7.0" upper_limit="8.0"/>
                    <measurement group_id="O3" value="8.0" lower_limit="7.0" upper_limit="9.0"/>
                    <measurement group_id="O4" value="8.0" lower_limit="7.0" upper_limit="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to ANC Nadir in Cycle 4</title>
        <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
        <time_frame>Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to ANC Nadir in Cycle 4</title>
          <description>Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="33"/>
                <count group_id="O4" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="8.0" upper_limit="NA">The upper limit of Kaplan-Meier 95% confidence interval was not estimable due to too many events at median value.</measurement>
                    <measurement group_id="O2" value="8.0" lower_limit="7.0" upper_limit="8.0"/>
                    <measurement group_id="O3" value="8.0" lower_limit="7.0" upper_limit="21.0"/>
                    <measurement group_id="O4" value="8.0" lower_limit="7.0" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4</title>
        <description>FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L..</description>
        <time_frame>Cycle 1 to Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4</title>
          <description>FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L..</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7"/>
                    <measurement group_id="O2" value="2.8"/>
                    <measurement group_id="O3" value="2.8"/>
                    <measurement group_id="O4" value="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.000</p_value>
            <method>Fisher Exact</method>
            <param_type>Percent Difference</param_type>
            <param_value>2.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20.2</ci_lower_limit>
            <ci_upper_limit>24.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.000</p_value>
            <method>Fisher Exact</method>
            <param_type>Percent Difference</param_type>
            <param_value>-2.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-26.7</ci_lower_limit>
            <ci_upper_limit>21.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.000</p_value>
            <method>Fisher Exact</method>
            <param_type>Percent Difference</param_type>
            <param_value>-2.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-26.7</ci_lower_limit>
            <ci_upper_limit>21.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities</title>
        <description>An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities (&quot;Hematology and Chemistry&quot;) were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated.</description>
        <time_frame>From the first dose up to 30 days post last dose of study drug (up to 4 months)</time_frame>
        <population>The Safety Population included all randomized participants who had received at least one dose of any protocol specified drug (i.e., docetaxel, cyclophosphamide, SPI-2012 or pegfilgrastim).</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities</title>
          <description>An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities (&quot;Hematology and Chemistry&quot;) were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated.</description>
          <population>The Safety Population included all randomized participants who had received at least one dose of any protocol specified drug (i.e., docetaxel, cyclophosphamide, SPI-2012 or pegfilgrastim).</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="39"/>
                <count group_id="O2" value="37"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3-4 TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="13"/>
                    <measurement group_id="O4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs Other Than Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Discontinuation From Study Therapy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3-4 Lab Abnormalities: Hematology</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3-4 Lab Abnormalities: Chemistry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4</title>
        <time_frame>All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O4">
            <title>Arm 4: Pegfilgrastim and TC</title>
            <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4</title>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="36"/>
                <count group_id="O4" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7"/>
                    <measurement group_id="O2" value="8.3"/>
                    <measurement group_id="O3" value="2.8"/>
                    <measurement group_id="O4" value="13.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.469</p_value>
            <method>Fisher Exact</method>
            <param_type>Percent Difference</param_type>
            <param_value>-6.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-28.5</ci_lower_limit>
            <ci_upper_limit>16.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.710</p_value>
            <method>Fisher Exact</method>
            <param_type>Percent Difference</param_type>
            <param_value>-5.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-29.3</ci_lower_limit>
            <ci_upper_limit>18.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.199</p_value>
            <method>Fisher Exact</method>
            <param_type>Percent Difference</param_type>
            <param_value>-11.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-34.6</ci_lower_limit>
            <ci_upper_limit>13.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Positive Antibodies for SPI-2012</title>
        <description>Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF.</description>
        <time_frame>Up to the end of the study (Approximately 3.5 months)</time_frame>
        <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed included participants who were treated with SPI-2012 and had post-treatment samples collected, and excluded participants who tested positive before being treated with SPI-2012. Data was collected and analyzed only for the &quot;SPI-2012&quot; reporting arms as per the planned analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Positive Antibodies for SPI-2012</title>
          <description>Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF.</description>
          <population>The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed included participants who were treated with SPI-2012 and had post-treatment samples collected, and excluded participants who tested positive before being treated with SPI-2012. Data was collected and analyzed only for the &quot;SPI-2012&quot; reporting arms as per the planned analysis.</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="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Concentration of SPI-2012 (Tmax)</title>
        <description>Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters.</description>
        <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and have sufficient number of blood samples. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Concentration of SPI-2012 (Tmax)</title>
          <description>Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters.</description>
          <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and have sufficient number of blood samples. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>hours (hrs)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.7" lower_limit="46.9" upper_limit="70.5"/>
                    <measurement group_id="O2" value="9.00" lower_limit="8" upper_limit="48.1"/>
                    <measurement group_id="O3" value="24.0" lower_limit="24" upper_limit="24.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Concentration of SPI-2012 (Cmax)</title>
        <description>Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
        <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Concentration of SPI-2012 (Cmax)</title>
          <description>Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
          <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>nanograms per milliliter (ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.00" spread="6.08"/>
                    <measurement group_id="O2" value="247" spread="276"/>
                    <measurement group_id="O3" value="299" spread="329"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)</title>
        <description>AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
        <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and have sufficient number of blood samples to estimate AUC. The AUC0-312 was not calculated for the 45 µg/kg dose due to insufficient data in the serum concentration profiles. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)</title>
          <description>AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
          <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and have sufficient number of blood samples to estimate AUC. The AUC0-312 was not calculated for the 45 µg/kg dose due to insufficient data in the serum concentration profiles. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>nanogram*hour per milliliter (ng*hr/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="16000" spread="5850"/>
                    <measurement group_id="O3" value="22900" spread="25100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Half-life of SPI-2012 (t1/2)</title>
        <description>t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
        <time_frame>Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)</time_frame>
        <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples to estimate AUC. The t1/2 was not calculated for the 45 µg/kg arm because there were insufficient data in terminal phase of serum concentration profiles. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
            <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
            <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
            <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Half-life of SPI-2012 (t1/2)</title>
          <description>t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.</description>
          <population>The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples to estimate AUC. The t1/2 was not calculated for the 45 µg/kg arm because there were insufficient data in terminal phase of serum concentration profiles. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.</population>
          <units>hrs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="81.0" spread="88.4"/>
                    <measurement group_id="O3" value="31.5" spread="NA">Standard deviation was not estimable since only 1 participant was evaluable.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose up to 30 days post last dose of study drug (up to 4 months)</time_frame>
      <desc>The Safety Population included all randomized participants who had received at least one dose of any protocol specified drug (i.e., docetaxel, cyclophosphamide, SPI-2012 or pegfilgrastim).</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm 1: SPI-2012 45 µg/kg and TC</title>
          <description>Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="E2">
          <title>Arm 2: SPI-2012 135 µg/kg and TC</title>
          <description>Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="E3">
          <title>Arm 3: SPI-2012 270 µg/kg and TC</title>
          <description>Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
        <group group_id="E4">
          <title>Arm 4: Pegfilgrastim and TC</title>
          <description>Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:&#xD;
Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (13.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="36"/>
              </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="2" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Gastritis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (13.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="35" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="20" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="36"/>
              </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="21" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="37"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="36"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="36"/>
              </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>Shanta Chawla</name_or_title>
      <organization>Spectrum Pharmaceuticals, Inc, Research and Development Office 157 Technology Drive Irvine, CA 92618</organization>
      <phone>(949) 788-6700</phone>
      <email>shanta.chawla@sppirx.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/NCT01724866
org study id: SPI-GCF-12-201
secondary id: 2013-003094-10
nct id: NCT01724866
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the effect of test doses of SPI-2012 on the duration
      of severe neutropenia (DSN) during Cycle 1 in participants with breast cancer who are
      candidates for adjuvant or neoadjuvant chemotherapy.
This is an open label, multicenter, dose ranging study, sequentially enrolled by study dose,
      with a non-inferiority design to compare the effectiveness of SPI-2012 relative to a fixed
      dose of pegfilgrastim as a concurrent active control to each dose of SPI-2012 in participants
      with breast cancer. This study included four arms comprising three dose levels of SPI-2012
      (Arm 1: 45 µg/kg, Arm 2: 135 µg/kg, Arm 3: 270 µg/kg) versus pegfilgrastim (Arm 4: 6 mg). The
      start of study is defined as the initiation of treatment with SPI-2012 or pegfilgrastim. The
      duration of treatment consists of a maximum of 4 cycles (21 days per cycle) beginning on Day
      1 with chemotherapy administration and continue through Day 21, plus a 30-day follow-up
      period, unless any of the discontinuation criteria applies.

      The target population are participants with breast cancer who are candidates for neoadjuvant
      or adjuvant treatment with Docetaxel + Cyclophosphamide (TC) chemotherapy. All participants
      who receive at least 1 dose of either SPI-2012 or pegfilgrastim were followed for safety
      through 30 days after their last dose of study treatment or until all treatment-related
      adverse events (AEs) have resolved or returned to baseline/Grade 1, whichever is longer, or
      until it is determined that the outcome will not change with further follow-up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Duration of Severe Neutropenia (DSN) in Cycle 1
time frame: Cycle 1 (each cycle was 21 days)
description: DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 1.
measure: Duration of DSN in Cycle 2
time frame: Cycle 2 (each cycle was 21 days)
description: DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 2.
measure: Duration of DSN in Cycle 3
time frame: Cycle 3 (each cycle was 21 days)
description: DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 3.
measure: Duration of DSN in Cycle 4
time frame: Cycle 4 (each cycle was 21 days)
description: DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 4.
measure: Time to ANC Recovery in Cycle 1
time frame: Cycle 1 (each cycle was 21 days)
description: Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥ 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1.
measure: Time to ANC Recovery in Cycle 2
time frame: Cycle 2 (each cycle was 21 days)
description: Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2.
measure: Time to ANC Recovery in Cycle 3
time frame: Cycle 3 (each cycle was 21 days)
description: Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3.
measure: Time to ANC Recovery in Cycle 4
time frame: Cycle 4 (each cycle was 21 days)
description: Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4.
measure: Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1
time frame: Cycle 1 (each cycle was 21 days)
description: Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.
measure: Absolute ANC Nadir Overtime in Cycle 2
time frame: Cycle 2 (each cycle was 21 days)
description: Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.
measure: Absolute ANC Nadir Overtime in Cycle 3
time frame: Cycle 3 (each cycle was 21 days)
description: Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.
measure: Absolute ANC Nadir Overtime in Cycle 4
time frame: Cycle 4 (each cycle was 21 days)
description: Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.
measure: Depth of ANC Nadir in Cycle 1
time frame: Cycle 1 (each cycle was 21 days)
description: Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.
measure: Depth of ANC Nadir in Cycle 2
time frame: Cycle 2 (each cycle was 21 days)
description: Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.
measure: Depth of ANC Nadir in Cycle 3
time frame: Cycle 3 (each cycle was 21 days)
description: Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.
measure: Depth of ANC Nadir in Cycle 4
time frame: Cycle 4 (each cycle was 21 days)
description: Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.
measure: Time to ANC Nadir in Cycle 1
time frame: Cycle 1 (each cycle was 21 days)
description: Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.
measure: Time to ANC Nadir in Cycle 2
time frame: Cycle 2 (each cycle was 21 days)
description: Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.
measure: Time to ANC Nadir in Cycle 3
time frame: Cycle 3 (each cycle was 21 days)
description: Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.
measure: Time to ANC Nadir in Cycle 4
time frame: Cycle 4 (each cycle was 21 days)
description: Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.
measure: Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4
time frame: Cycle 1 to Cycle 4 (each cycle was 21 days)
description: FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L..
measure: Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities
time frame: From the first dose up to 30 days post last dose of study drug (up to 4 months)
description: An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities ("Hematology and Chemistry") were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated.
measure: Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4
time frame: All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)
measure: Number of Participants With Positive Antibodies for SPI-2012
time frame: Up to the end of the study (Approximately 3.5 months)
description: Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF.
measure: Time to Reach Maximum Concentration of SPI-2012 (Tmax)
time frame: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
description: Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters.
measure: Maximum Concentration of SPI-2012 (Cmax)
time frame: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
description: Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.
measure: Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)
time frame: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
description: AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.
measure: Half-life of SPI-2012 (t1/2)
time frame: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
description: t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.
arm group label: Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group type: Experimental
description: Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
arm group label: Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group type: Experimental
description: Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
arm group label: Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group type: Experimental
description: Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
arm group label: Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
arm group type: Experimental
description: Participants received Pegfilgrastim 6 milligram (mg), SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
intervention type: Drug
intervention name: SPI-2012
description: SPI-2012 SC injection.
arm group label: Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
other name: Rolontis®
other name: HM10460A
other name: Eflapegrastim
intervention type: Drug
intervention name: Pegfilgrastim
description: Pegfilgrastim SC injection, per manufacturer's Prescribing Information.
arm group label: Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
other name: Neulasta®
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel given based on standard dose for chemotherapy.
arm group label: Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
other name: Taxotere
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide given based on standard dose for chemotherapy.
arm group label: Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)
arm group label: Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
other name: Cytoxan
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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facility: 
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country: Australia
country: Georgia
country: Hungary
country: Israel
country: Poland
country: United States
country: Canada
country: Czech Republic
country: Czechia
responsible party type: Sponsor
mesh term: Neutropenia
mesh term: Cyclophosphamide
mesh term: Docetaxel
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 