<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/NCT02990468</url>
  </required_header>
  <id_info>
    <org_study_id>BMX-HN-001</org_study_id>
    <nct_id>NCT02990468</nct_id>
  </id_info>
  <brief_title>A Trial of Concurrent Radiation Therapy, Cisplatin, and BMX-001 in Locally Advanced Head and Neck Cancer</brief_title>
  <acronym>BMX-HN</acronym>
  <official_title>A Phase 1 / Phase 2 Trial of Concurrent Radiation Therapy, Cisplatin, and BMX-001 in Locally Advanced Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioMimetix JV, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>BioMimetix JV, LLC</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a Phase 1 / Phase 2 study of newly diagnosed patients with biopsy-proven head and&#xD;
      neck cancer (squamous cell carcinoma) who are undergoing standard radiation therapy and&#xD;
      treatment with cisplatin. BMX-001 added to radiation therapy and cisplatin is expected to&#xD;
      reduce radiation-induced mucositis and xerostomia and also has the potential to benefit the&#xD;
      survival of head and neck cancer patients. In Phase 1, safety and tolerability of BMX-001&#xD;
      will be assessed using a Continual Reassessment Method (CRM) and a maximum tolerated dose&#xD;
      (MTD) will be determined. BMX-001 will be given subcutaneously first with a loading dose zero&#xD;
      to four days prior to the start of chemoradiation and followed by twice a week doses at&#xD;
      one-half of the loading dose for the duration of radiation therapy plus two weeks. In Phase 2&#xD;
      both safety and efficacy of BMX-001 will be evaluated. Impact on mucositis and xerostomia&#xD;
      will also be assessed. A maximum of 48 patients will be enrolled to the MTD dose determined&#xD;
      in Phase 1 to confirm the MTD. The investigators hypothesize that BMX-001 when added to&#xD;
      standard radiation therapy and cisplatin will be safe at pharmacologically relevant doses in&#xD;
      patients with newly diagnosed head and neck cancer. The investigators also hypothesize that&#xD;
      in Phase 2 of this study the addition of BMX-001 will reduce the severity of&#xD;
      radiation-induced mucositis and xerostomia in patients receiving head and neck radiation&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 19, 2017</start_date>
  <completion_date type="Actual">March 31, 2022</completion_date>
  <primary_completion_date type="Actual">February 21, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Dose escalation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the Safety of the Study Drug by Calculating the Proportion of Patients Who Experience Grade 4 or 5 Study Drug Related Adverse Events, as Assessed by CTCAE v 4.03.</measure>
    <time_frame>1 year</time_frame>
    <description>This outcome is to confirm the safety and tolerability of escalating doses of BMX-001 in conjunction with RT and concurrent cisplatin in a cohort of newly diagnosed patients with locally advanced head and neck cancers. Each dose will be reported separately.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence Radiation-induced Mucositis by Clinician Scoring</measure>
    <time_frame>6 months</time_frame>
    <description>Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Higher scores are indicative of worse symptoms. Grade 0-5. We are reporting the incidence of the patients that had mucositis grade 1-5.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Radiation-induced Xerostomia by Stimulated Saliva Production</measure>
    <time_frame>6 months</time_frame>
    <description>Xerostomia will also be assessed by measurement of stimulated saliva production posttreatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Radiation-induced Xerostomia by Unstimulated Saliva Production</measure>
    <time_frame>6 months</time_frame>
    <description>Xerostomia will also be assessed by measurement of unstimulated saliva production post treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Radiation-induced Xerostomia by Clinician Scoring</measure>
    <time_frame>6 months</time_frame>
    <description>Xerostomia will be assessed using Maximum Xerostomia Clinical Score Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Scores range from 0 to 5 with 0 being no xerostomia and 5 being the worst. Mean maximum xerostomia grade of patients assessed is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Radiation-induced Mucositis</measure>
    <time_frame>6 month 6 months</time_frame>
    <description>Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Duration of Oral Mucositis WHO Grade 3 or higher measured as the days of severe oral mucositis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To Examine the Impact on Radiation Dermatitis When Adding BMX-001 to Treatment</measure>
    <time_frame>30 days</time_frame>
    <description>To examine the impact on radiation dermatitis of BMX-001 in combination with RT and concurrent cisplatin at 30-39 Gy, 40-49 Gy, 50-59 Gy, and 60-70 Gy, the duration of radiation dermatitis, and evaluation of radiation dermatitis-related patient-reported outcomes</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Radiation Therapy, Cisplatin and BMX-001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Phase 1, safety and tolerability of BMX-001 will be assessed using a Continual Reassessment Method and a maximum tolerated dose (MTD) will be determined using a single arm design. In Phase 2, the severity of radiation-induced mucositis and xerostomia will be assessed using a single arm design.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMX-001</intervention_name>
    <description>Subcutaneous injection.</description>
    <arm_group_label>Radiation Therapy, Cisplatin and BMX-001</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Patients will receive standard dose intensity modulated radiation therapy (IMRT).</description>
    <arm_group_label>Radiation Therapy, Cisplatin and BMX-001</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin will be administered per institution's standard of care practice.</description>
    <arm_group_label>Radiation Therapy, Cisplatin and BMX-001</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx,&#xD;
             larynx, hypopharynx, or oral cavity with clinical or pathologic high-risk features for&#xD;
             whom cisplatin and radiation would be considered appropriate care.&#xD;
&#xD;
          2. Treatment plan to receive a continuous course of IMRT delivered as single daily&#xD;
             fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy&#xD;
             depending on whether patients are considered post-operative high risk or&#xD;
             unresectable/organ preservation high risk. Planned radiation treatment fields must&#xD;
             include at least two oral sites buccal mucosa, retromolar trigone, floor of mouth,&#xD;
             oral tongue, soft palate, hard palate) with a portion of each site receiving a minimum&#xD;
             total of 50 Gy.&#xD;
&#xD;
          3. Patients who are to undergo definitive chemoradiation must have clinically or&#xD;
             radiographically evident measurable disease at the primary site and/or at nodal&#xD;
             stations. Tonsillectomy or local excision of the primary without removal of nodal&#xD;
             disease is permitted.&#xD;
&#xD;
          4. Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as&#xD;
             non-therapeutic nodal excisions. Fine needle aspirations of the neck that are positive&#xD;
             for squamous cell carcinoma are sufficient for diagnosis pending pathology review at&#xD;
             participating institutions.&#xD;
&#xD;
          5. For patients undergoing curative intent resection the following criteria are required:&#xD;
&#xD;
               -  Pathologically (histologically or cytologically) proven diagnosis of head and&#xD;
                  neck squamous cell carcinoma&#xD;
&#xD;
               -  Patients must have undergone gross total surgical resection within 42 days prior&#xD;
                  to registration and beginning of therapy under the clinical trial. Note: Patients&#xD;
                  may have biopsy under general anesthesia in an operating room followed by&#xD;
                  definitive ablative cancer surgery representing gross total resection.&#xD;
&#xD;
          6. Clinical or pathologic stage Stage III-IVb per the American Joint Committee on Cancer&#xD;
             (AJCC), 7th edition.&#xD;
&#xD;
          7. General history and physical examination by a radiation oncologist and medical&#xD;
             oncologist within 4 weeks prior to enrollment.&#xD;
&#xD;
          8. Examination by an ear/nose/throat (ENT) or head and neck surgeon, including&#xD;
             laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks&#xD;
             prior to enrollment.&#xD;
&#xD;
          9. Zubrod Performance Status 0-2 within 4 weeks prior to enrollment&#xD;
&#xD;
         10. Complete blood count (CBC)/differential obtained within 7 days prior to starting the&#xD;
             study drug with adequate bone marrow function, defined as follows:&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dl;&#xD;
&#xD;
               -  Platelets ≥ 100,000 cells/mm3;&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt; 1,500 cell/mm3.&#xD;
&#xD;
         11. Adequate hepatic function as defined as follows:&#xD;
&#xD;
               -  Total bilirubin &lt; 2x institutional upper limit of normal (ULN) within 7 days&#xD;
                  prior to starting the study drug;&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and AST &lt;3x institutional ULN within 7 days&#xD;
                  prior to starting the study drug.&#xD;
&#xD;
         12. Adequate renal function defined as follows:&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 mg/dl within 7 days prior to starting the study drug or&#xD;
                  creatinine clearance rate (CCr) ≥ 50 mL/min within 7 days prior to starting the&#xD;
                  study drug determined by 24-hour collection or estimated by Cockcroft-Gault&#xD;
                  formula:&#xD;
&#xD;
             CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x&#xD;
             (CrCl male)&#xD;
&#xD;
         13. Negative pregnancy test for women of child-bearing potential within 48 hours prior to&#xD;
             first dose of BMX-001.&#xD;
&#xD;
         14. Women of childbearing potential and male participants must agree to use a medically&#xD;
             effective means of birth control throughout their participation in the treatment phase&#xD;
             of the study and until 12 months following the last study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Stage I or II; T1N1 and T2N1 stage III presentations per AJCC 7th edition&#xD;
&#xD;
          2. Distant metastasis&#xD;
&#xD;
          3. Hypertension requiring 3 or more anti-hypertensive medications to control&#xD;
&#xD;
          4. Grade ≥2 hypotension at screening&#xD;
&#xD;
          5. Requirement for concurrent treatment with nitrates or other drugs that may, in the&#xD;
             judgment of the treating investigator, create a risk for a precipitous decrease in&#xD;
             blood pressure&#xD;
&#xD;
          6. History of syncope within the last 6 months&#xD;
&#xD;
          7. Patients receiving, or unable to stop use at least 1 week prior to receiving the first&#xD;
             dose of BMX-001, medications listed in Section 12.2 of the protocol are not eligible.&#xD;
&#xD;
          8. Pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception; this exclusion is&#xD;
             necessary because the treatment involved in this study may be significantly&#xD;
             teratogenic&#xD;
&#xD;
          9. Women who are breast feeding are not eligible&#xD;
&#xD;
         10. Prior allergic reaction to cisplatin&#xD;
&#xD;
         11. Known hypersensitivity to compounds of similar chemical composition to BMX-001&#xD;
&#xD;
         12. Grade 3-4 electrolyte abnormalities (CTCAE v 4.03) except sodium, which must be ≥126&#xD;
             mmol/L.&#xD;
&#xD;
         13. Prior unrelated malignancy requiring current active treatment with the exception of&#xD;
             cervical carcinoma in situ, basal cell carcinoma of the skin, resected T1-2N0M0&#xD;
             differentiated thyroid cancers, invasive cancers with a 3-year disease-free interval,&#xD;
             Ta bladder cancers, or low and favorable intermediate risk prostate cancer.&#xD;
&#xD;
         14. Prior history of HNSCC receiving radiation or chemo-radiation.&#xD;
&#xD;
         15. Prior systemic chemotherapy for the study cancer (including neoadjuvant chemotherapy);&#xD;
             note that prior chemotherapy for a different cancer is allowable.&#xD;
&#xD;
         16. Prior radiotherapy that would result in overlap of radiation treatment fields with&#xD;
             planned treatment for study cancer.&#xD;
&#xD;
         17. Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Cardiovascular disease or cerebrovascular disease, for example cerebrovascular&#xD;
                  accidents or myocardial infarction ≤ 6 months prior to study enrollment, unstable&#xD;
                  angina, New York Heart Association (NYHA) Grade II or greater congestive heart&#xD;
                  failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or with&#xD;
                  the potential to interfere with protocol treatment;&#xD;
&#xD;
               -  Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or&#xD;
                  recent arterial thrombosis) within 6 months prior to enrollment;&#xD;
&#xD;
               -  History or evidence upon physical/neurological examination of central nervous&#xD;
                  system disease (e.g., seizures) unrelated to cancer unless adequately controlled&#xD;
                  by medication;&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics within 7&#xD;
                  days of enrollment;&#xD;
&#xD;
               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy within 30 days of&#xD;
                  registration;&#xD;
&#xD;
               -  Patients known to be HIV positive or have active viral hepatitis.&#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>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida- Gainesville</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <results_first_submitted>November 16, 2022</results_first_submitted>
  <results_first_submitted_qc>February 16, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 15, 2023</results_first_posted>
  <last_update_submitted>February 16, 2023</last_update_submitted>
  <last_update_submitted_qc>February 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mucositis</keyword>
  <keyword>Xerostomia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/68/NCT02990468/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/68/NCT02990468/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Phase 1: Group 1</title>
          <description>Participants were administered a 7 mg loading dose followed by a 3.5 mg maintenance dose twice a week for up to 8 weeks while receiving concurrent cisplatin and RT.</description>
        </group>
        <group group_id="P2">
          <title>Phase 1: Group II</title>
          <description>Participants were administered a 14 mg loading dose followed by a 7 mg maintenance dose twice a week for up to 8 weeks while receiving concurrent cisplatin and RT.</description>
        </group>
        <group group_id="P3">
          <title>Phase 2: Group III - MTD</title>
          <description>Participants were administered a 28 mg loading dose followed by a 14 mg maintenance dose twice a week for up to 8 weeks while receiving concurrent cisplatin and RT.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1: Dose Escalation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Phase 2: MTD</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Change in treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>dose escalation</population>
      <group_list>
        <group group_id="B1">
          <title>Phase 1: Group I</title>
          <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
        </group>
        <group group_id="B2">
          <title>Phase 1: Group II</title>
          <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
        </group>
        <group group_id="B3">
          <title>Phase 2: Group III</title>
          <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
        </group>
        <group group_id="B4">
          <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="3"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="23"/>
            <count group_id="B4" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="57.33" spread="12.97"/>
                    <measurement group_id="B2" value="67.67" spread="4.91"/>
                    <measurement group_id="B3" value="60.96" spread="7.66"/>
                    <measurement group_id="B4" value="61.28" spread="8.51"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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_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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Assess the Safety of the Study Drug by Calculating the Proportion of Patients Who Experience Grade 4 or 5 Study Drug Related Adverse Events, as Assessed by CTCAE v 4.03.</title>
        <description>This outcome is to confirm the safety and tolerability of escalating doses of BMX-001 in conjunction with RT and concurrent cisplatin in a cohort of newly diagnosed patients with locally advanced head and neck cancers. Each dose will be reported separately.</description>
        <time_frame>1 year</time_frame>
        <population>Each dosing group reported seperately.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>Assess the Safety of the Study Drug by Calculating the Proportion of Patients Who Experience Grade 4 or 5 Study Drug Related Adverse Events, as Assessed by CTCAE v 4.03.</title>
          <description>This outcome is to confirm the safety and tolerability of escalating doses of BMX-001 in conjunction with RT and concurrent cisplatin in a cohort of newly diagnosed patients with locally advanced head and neck cancers. Each dose will be reported separately.</description>
          <population>Each dosing group reported seperately.</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="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="23"/>
              </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="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Incidence Radiation-induced Mucositis by Clinician Scoring</title>
        <description>Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Higher scores are indicative of worse symptoms. Grade 0-5. We are reporting the incidence of the patients that had mucositis grade 1-5.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence Radiation-induced Mucositis by Clinician Scoring</title>
          <description>Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Higher scores are indicative of worse symptoms. Grade 0-5. We are reporting the incidence of the patients that had mucositis grade 1-5.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Radiation-induced Xerostomia by Stimulated Saliva Production</title>
        <description>Xerostomia will also be assessed by measurement of stimulated saliva production posttreatment.</description>
        <time_frame>6 months</time_frame>
        <population>one subject in group 3 did not complete follow up and was excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Radiation-induced Xerostomia by Stimulated Saliva Production</title>
          <description>Xerostomia will also be assessed by measurement of stimulated saliva production posttreatment.</description>
          <population>one subject in group 3 did not complete follow up and was excluded from analysis</population>
          <units>gram</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="3"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.487" spread="0.144"/>
                    <measurement group_id="O2" value="2.387" spread="0.688"/>
                    <measurement group_id="O3" value="2.115" spread="1.151"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Radiation-induced Xerostomia by Unstimulated Saliva Production</title>
        <description>Xerostomia will also be assessed by measurement of unstimulated saliva production post treatment.</description>
        <time_frame>6 months</time_frame>
        <population>one subject in group 3 did not complete follow up and was excluded from analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Radiation-induced Xerostomia by Unstimulated Saliva Production</title>
          <description>Xerostomia will also be assessed by measurement of unstimulated saliva production post treatment.</description>
          <population>one subject in group 3 did not complete follow up and was excluded from analysis</population>
          <units>gram</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.42" spread="0.041"/>
                    <measurement group_id="O2" value="1.090" spread="0.334"/>
                    <measurement group_id="O3" value="1.255" spread="0.932"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Radiation-induced Xerostomia by Clinician Scoring</title>
        <description>Xerostomia will be assessed using Maximum Xerostomia Clinical Score Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Scores range from 0 to 5 with 0 being no xerostomia and 5 being the worst. Mean maximum xerostomia grade of patients assessed is reported.</description>
        <time_frame>6 months</time_frame>
        <population>One subject in group 3 did not complete follow up and was excluded from the analysis (a score of 0 representing no xerostomia)</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Radiation-induced Xerostomia by Clinician Scoring</title>
          <description>Xerostomia will be assessed using Maximum Xerostomia Clinical Score Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Scores range from 0 to 5 with 0 being no xerostomia and 5 being the worst. Mean maximum xerostomia grade of patients assessed is reported.</description>
          <population>One subject in group 3 did not complete follow up and was excluded from the analysis (a score of 0 representing no xerostomia)</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0"/>
                    <measurement group_id="O2" value="1.33" spread="0.27"/>
                    <measurement group_id="O3" value="1.29" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Radiation-induced Mucositis</title>
        <description>Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Duration of Oral Mucositis WHO Grade 3 or higher measured as the days of severe oral mucositis.</description>
        <time_frame>6 month 6 months</time_frame>
        <population>only the patients that had mucositis were evaluated for duration</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Radiation-induced Mucositis</title>
          <description>Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Duration of Oral Mucositis WHO Grade 3 or higher measured as the days of severe oral mucositis.</description>
          <population>only the patients that had mucositis were evaluated for duration</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22" spread="NA">The sample size is too small to calculate standard error.</measurement>
                    <measurement group_id="O2" value="18" spread="NA">The sample size is too small to calculate standard error.</measurement>
                    <measurement group_id="O3" value="37.4" spread="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>To Examine the Impact on Radiation Dermatitis When Adding BMX-001 to Treatment</title>
        <description>To examine the impact on radiation dermatitis of BMX-001 in combination with RT and concurrent cisplatin at 30-39 Gy, 40-49 Gy, 50-59 Gy, and 60-70 Gy, the duration of radiation dermatitis, and evaluation of radiation dermatitis-related patient-reported outcomes</description>
        <time_frame>30 days</time_frame>
        <population>Data was not collected or analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Group 1</title>
            <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Group II</title>
            <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Group III</title>
            <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
          </group>
        </group_list>
        <measure>
          <title>To Examine the Impact on Radiation Dermatitis When Adding BMX-001 to Treatment</title>
          <description>To examine the impact on radiation dermatitis of BMX-001 in combination with RT and concurrent cisplatin at 30-39 Gy, 40-49 Gy, 50-59 Gy, and 60-70 Gy, the duration of radiation dermatitis, and evaluation of radiation dermatitis-related patient-reported outcomes</description>
          <population>Data was not collected or analyzed</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time the subject signs the informed consent form through and of treatment visit (one year follow up)</time_frame>
      <desc>An AE can therefore be any unfavorable and unintended or worsening sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of BMX-001, whether or not related to use of the BMX-001. Abnormal laboratory findings without clinical significance (based on the PI's judgment) should not be recorded as AEs, but laboratory value changes that require therapy or adjustment in prior therapy are considered adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Group I</title>
          <description>Subjects were administered a 7 mg loading dose subcutaneously followed by a 3.5 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
        </group>
        <group group_id="E2">
          <title>Phase 1: Group II</title>
          <description>Subjects were administered a 14 mg loading dose subcutaneously followed by a 7 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
        </group>
        <group group_id="E3">
          <title>Phase 2: Group III</title>
          <description>Subjects were administered a 28 mg loading dose subcutaneously followed by a 14 mg maintenance dose subcutaneously twice a week while on concurrent cisplatin and RT.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</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="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Gastronomy failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Neutropenic colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lymphoedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Conduction Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypoacusis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Middle ear adhesions</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Anal incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Early satiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lip pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Salivary duct inflammation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Feeling jittery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Deafness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Skin disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Skin mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Telangiectasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </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 NOT 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>
    <limitations_and_caveats>This was a dose escalation study with all subjects receiving the intervention. There was no control arm for comparison. This will be addressed in a future clinical trial. This study design was effective for a safety, dose-escalation study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Director of Clinical Operations</name_or_title>
      <organization>BioMimetix JV LLC</organization>
      <phone>303-862-7268</phone>
      <email>contact@bmxpharma.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/NCT02990468
org study id: BMX-HN-001
nct id: NCT02990468
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1 / Phase 2 study of newly diagnosed patients with biopsy-proven head and
      neck cancer (squamous cell carcinoma) who are undergoing standard radiation therapy and
      treatment with cisplatin. BMX-001 added to radiation therapy and cisplatin is expected to
      reduce radiation-induced mucositis and xerostomia and also has the potential to benefit the
      survival of head and neck cancer patients. In Phase 1, safety and tolerability of BMX-001
      will be assessed using a Continual Reassessment Method (CRM) and a maximum tolerated dose
      (MTD) will be determined. BMX-001 will be given subcutaneously first with a loading dose zero
      to four days prior to the start of chemoradiation and followed by twice a week doses at
      one-half of the loading dose for the duration of radiation therapy plus two weeks. In Phase 2
      both safety and efficacy of BMX-001 will be evaluated. Impact on mucositis and xerostomia
      will also be assessed. A maximum of 48 patients will be enrolled to the MTD dose determined
      in Phase 1 to confirm the MTD. The investigators hypothesize that BMX-001 when added to
      standard radiation therapy and cisplatin will be safe at pharmacologically relevant doses in
      patients with newly diagnosed head and neck cancer. The investigators also hypothesize that
      in Phase 2 of this study the addition of BMX-001 will reduce the severity of
      radiation-induced mucositis and xerostomia in patients receiving head and neck radiation
      therapy.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Dose escalation
primary purpose: Treatment
masking: None (Open Label)
measure: Assess the Safety of the Study Drug by Calculating the Proportion of Patients Who Experience Grade 4 or 5 Study Drug Related Adverse Events, as Assessed by CTCAE v 4.03.
time frame: 1 year
description: This outcome is to confirm the safety and tolerability of escalating doses of BMX-001 in conjunction with RT and concurrent cisplatin in a cohort of newly diagnosed patients with locally advanced head and neck cancers. Each dose will be reported separately.
measure: Incidence Radiation-induced Mucositis by Clinician Scoring
time frame: 6 months
description: Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Higher scores are indicative of worse symptoms. Grade 0-5. We are reporting the incidence of the patients that had mucositis grade 1-5.
measure: Incidence of Radiation-induced Xerostomia by Stimulated Saliva Production
time frame: 6 months
description: Xerostomia will also be assessed by measurement of stimulated saliva production posttreatment.
measure: Incidence of Radiation-induced Xerostomia by Unstimulated Saliva Production
time frame: 6 months
description: Xerostomia will also be assessed by measurement of unstimulated saliva production post treatment.
measure: Incidence of Radiation-induced Xerostomia by Clinician Scoring
time frame: 6 months
description: Xerostomia will be assessed using Maximum Xerostomia Clinical Score Common Terminology Criteria for Adverse Events (CTCAE) 4.03. Scores range from 0 to 5 with 0 being no xerostomia and 5 being the worst. Mean maximum xerostomia grade of patients assessed is reported.
measure: Duration of Radiation-induced Mucositis
time frame: 6 month 6 months
description: Mucositis will be scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Duration of Oral Mucositis WHO Grade 3 or higher measured as the days of severe oral mucositis.
measure: To Examine the Impact on Radiation Dermatitis When Adding BMX-001 to Treatment
time frame: 30 days
description: To examine the impact on radiation dermatitis of BMX-001 in combination with RT and concurrent cisplatin at 30-39 Gy, 40-49 Gy, 50-59 Gy, and 60-70 Gy, the duration of radiation dermatitis, and evaluation of radiation dermatitis-related patient-reported outcomes
arm group label: Radiation Therapy, Cisplatin and BMX-001
arm group type: Experimental
description: In Phase 1, safety and tolerability of BMX-001 will be assessed using a Continual Reassessment Method and a maximum tolerated dose (MTD) will be determined using a single arm design. In Phase 2, the severity of radiation-induced mucositis and xerostomia will be assessed using a single arm design.
intervention type: Drug
intervention name: BMX-001
description: Subcutaneous injection.
arm group label: Radiation Therapy, Cisplatin and BMX-001
intervention type: Radiation
intervention name: Radiation Therapy
description: Patients will receive standard dose intensity modulated radiation therapy (IMRT).
arm group label: Radiation Therapy, Cisplatin and BMX-001
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin will be administered per institution's standard of care practice.
arm group label: Radiation Therapy, Cisplatin and BMX-001
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Cisplatin
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This was a dose escalation study with all subjects receiving the intervention. There was no control arm for comparison. This will be addressed in a future clinical trial. This study design was effective for a safety, dose-escalation study.
point of contact: 