<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/NCT01684566</url>
  </required_header>
  <id_info>
    <org_study_id>HS-10-396</org_study_id>
    <nct_id>NCT01684566</nct_id>
  </id_info>
  <brief_title>A Comparative Investigation of Standard Of Care (SOC) and Episil® in Combination Versus SOC Alone on Oral Mucositis</brief_title>
  <acronym>episil(R)</acronym>
  <official_title>A Multicenter, Open-label, Parallel Group Investigation to Compare the Performance of Standard Of Care (SOC) and Episil® in Combination Versus SOC Alone on Oral Mucositis in Patients Receiving Conditioning Treatment for Hematopoietic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Camurus AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Camurus AB</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the performance of standard of care (SOC) + episil® versus SOC alone on oral&#xD;
      mucositis in patients receiving conditioning treatment for hematopoietic stem cell&#xD;
      transplantation (HSCT). The primary variable will be the area under the curve (AUC) of oral&#xD;
      mucositis scores defined by the World Health Organisation (WHO) oral toxicity scale assessed&#xD;
      daily by the investigator over the 28-day study period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was multicentre, open-label, randomised parallel-group study. Patients were randomised&#xD;
      to one of two parallel treatment groups: episil® in combination with SOC or SOC alone.&#xD;
&#xD;
      The study was originally planned to be conducted in several sites in the following countries:&#xD;
      Denmark, Israel, Poland, and Sweden. Following a country-specific Amendment on 20-Feb-2013&#xD;
      and a German Ethical Committee (EC) approval in 07-May-2013, Germany was added to the list of&#xD;
      countries where the study would be conducted. No study sites were initiated in Denmark.&#xD;
&#xD;
      The study design was aimed to facilitate direct comparison of the performance of SOC +&#xD;
      episil® versus SOC alone. The study was conducted in an open-label manner that is common in&#xD;
      trials involving cancer patients, as this takes into the account the ethical issues involved&#xD;
      in this indication and patient population. To reduce the likelihood of bias, assignment to&#xD;
      study treatment was randomised.&#xD;
&#xD;
      SOC as control group is appropriate and widely used, especially in trials involving cancer&#xD;
      patients. In this particular study, basic oral hygiene consisting of brushing, flossing,&#xD;
      rinsing and moisturising was taken as the SOC used as control group.&#xD;
&#xD;
      .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">September 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population</measure>
    <time_frame>28 days</time_frame>
    <description>Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
  </primary_outcome>
  <primary_outcome>
    <measure>WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population</measure>
    <time_frame>28 days</time_frame>
    <description>Summary of WHO (World Health Organisation) Oral Toxicity Scores AUC Over the 28-Day Period Per protocol population.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Oral Mucositis</measure>
    <time_frame>28 days</time_frame>
    <description>Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organization) oral toxicity scale grade 0-4.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Oral Mucositis, Intention to Treat Population</measure>
    <time_frame>28 days</time_frame>
    <description>Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis was graded according to WHO 5 Point grading scale on a daily basis.&#xD;
Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Mucositis Daily Questionnaire (OMDQ)</measure>
    <time_frame>28 days</time_frame>
    <description>OMDQ (Oral Mucositis Daily Questionnaire) scale was used to measure Overall Mouth and Throat Soreness This was scored from 0=no soreness to 10=worst possible soreness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Mucositis Assessment Scale (OMAS)</measure>
    <time_frame>28 days</time_frame>
    <description>Summary of Oral Mucositis Assessment Scale (OMAS) Ulceration and Erythema Scores Extent of ulceration (grade 0-3) and severity of erythema (grade 0-2) according to the OMAS (Oral Mucositis Assessment Scale) assessed by a dental practitioner twice-weekly over the 28-day study period.&#xD;
The extent of ulceration was rated as follows:&#xD;
0 no lesion&#xD;
1 cm2&#xD;
1-3 cm2&#xD;
&gt;3 cm2&#xD;
The severity of erythema was assessed as follows:&#xD;
0 none&#xD;
not severe&#xD;
severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Stay, Days</measure>
    <time_frame>28 days</time_frame>
    <description>Duration of hospital stay (time from admission to discharge)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence of Oral Mucositis, Per Protocol Population</measure>
    <time_frame>28 days</time_frame>
    <description>Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organisation) oral toxicity scale grade 0-4&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Oral Mucositis, Per Protocol Population</measure>
    <time_frame>28 days</time_frame>
    <description>Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis is graded according to the 5-point oral mucositis WHO scale Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Oral Mucositis</condition>
  <arm_group>
    <arm_group_label>Standard-Of-Care + episil(R)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard-Of-Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Oral hygiene procedures</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>episil(R)</intervention_name>
    <description>episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.</description>
    <arm_group_label>Standard-Of-Care + episil(R)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral hygiene procedures</intervention_name>
    <description>Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
    <arm_group_label>Standard-Of-Care</arm_group_label>
    <arm_group_label>Standard-Of-Care + episil(R)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Is at least 18 years of age.&#xD;
&#xD;
          2. Has a confirmed diagnosis for which he/she is scheduled for hematopoietic stem cell&#xD;
             transplantation (HSCT) of either type of transplant (autologous or allogeneic).&#xD;
&#xD;
          3. Is due to undergo treatment with myeloablative conditioning (radiation-based or non&#xD;
             radiation based) before HSCT.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Will undergo reduced intensity conditioning before HSCT.&#xD;
&#xD;
          2. Has got known allergy to any ingredient in the study product or to peanuts, peppermint&#xD;
             oil, or soya.&#xD;
&#xD;
          3. Is pregnant or breast feeding.&#xD;
&#xD;
          4. Has any other concurrent medical condition that, in the opinion of the investigator,&#xD;
             would increase the risk to the patient, compromise evaluation of the investigational&#xD;
             device, or interfere with the conduct of the study.&#xD;
&#xD;
          5. Has an unstable condition (eg, a psychiatric disorder, a recent history of substance&#xD;
             abuse) or is otherwise thought to be unreliable or incapable of complying with the&#xD;
             study requirements.&#xD;
&#xD;
          6. Is undergoing treatment with parenteral opioids at enrolment.&#xD;
&#xD;
          7. Uses treatments that promote mucosal healing (eg, palifermin).&#xD;
&#xD;
          8. Uses electrolyte mouthwashes (eg, Caphosol®) or other topical oral treatments (eg,&#xD;
             Tantum Verde® (benzydamine), Gelclair®, Fungicidin (nystatin)).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karin Garming-Legert, DDS, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet, Stockholm, Sweden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Med Klinik und Poliklinik I Universitatsklinikum Carl Gustav Carus</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abteilung fur Hamatologie und Onkologie Universitatsmedizin an der Georg-August-Universitat</name>
      <address>
        <city>Gottingen</city>
        <zip>37099</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Health Care Campus</name>
      <address>
        <city>Haifa</city>
        <zip>31096</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Centre</name>
      <address>
        <city>Jerusalem</city>
        <zip>91240</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah Tikva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Tel-Aviv Sourasky Medical Centre</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Military Institute of Medicine Internal diseases and Haemtalogy Clinic</name>
      <address>
        <city>Warszawa</city>
        <zip>01141</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Haematology and Transfusion Medicine</name>
      <address>
        <city>Warszawa</city>
        <zip>02776</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Center Institute named Maria Sklodowska-Curie Lymph System Cancer Clinic</name>
      <address>
        <city>Warszawa</city>
        <zip>02781</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karin Garming-Legert</name>
      <address>
        <city>Stockholm</city>
        <state>Huddinge</state>
        <zip>141 04</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lund University Hospital</name>
      <address>
        <city>Lund</city>
        <zip>22185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uppsala University Hospital</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Israel</country>
    <country>Poland</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>November 12, 2015</results_first_submitted>
  <results_first_submitted_qc>February 17, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 14, 2016</results_first_posted>
  <last_update_submitted>February 17, 2016</last_update_submitted>
  <last_update_submitted_qc>February 17, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucositis</mesh_term>
    <mesh_term>Stomatitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Standard-Of-Care + Episil(R)</title>
          <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
        </group>
        <group group_id="P2">
          <title>Standard-Of-Care</title>
          <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="60"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated (ITT)</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="49"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intention to treat (ITT)</population>
      <group_list>
        <group group_id="B1">
          <title>Standard-Of-Care + Episil(R)</title>
          <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
        </group>
        <group group_id="B2">
          <title>Standard-Of-Care</title>
          <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="57"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="109"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.4" spread="15.21"/>
                    <measurement group_id="B2" value="49.0" spread="14.82"/>
                    <measurement group_id="B3" value="47.6" spread="15.01"/>
                  </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="27"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="67"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="107"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Sweden</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population</title>
        <description>Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
        <time_frame>28 days</time_frame>
        <population>Intention to treat (ITT) and Last observation carried forward (LOCF)</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population</title>
          <description>Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
          <population>Intention to treat (ITT) and Last observation carried forward (LOCF)</population>
          <units>score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.63" spread="0.702"/>
                    <measurement group_id="O2" value="0.56" spread="0.589"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Oral Mucositis</title>
        <description>Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organization) oral toxicity scale grade 0-4.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
        <time_frame>28 days</time_frame>
        <population>Intention to treat (ITT)</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Oral Mucositis</title>
          <description>Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organization) oral toxicity scale grade 0-4.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
          <population>Intention to treat (ITT)</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Oral Mucositis, Intention to Treat Population</title>
        <description>Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis was graded according to WHO 5 Point grading scale on a daily basis.&#xD;
Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
        <time_frame>28 days</time_frame>
        <population>ITT (Intention to treat). There were13 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Oral Mucositis, Intention to Treat Population</title>
          <description>Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis was graded according to WHO 5 Point grading scale on a daily basis.&#xD;
Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
          <population>ITT (Intention to treat). There were13 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.5" spread="6.85"/>
                    <measurement group_id="O2" value="10.7" spread="6.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oral Mucositis Daily Questionnaire (OMDQ)</title>
        <description>OMDQ (Oral Mucositis Daily Questionnaire) scale was used to measure Overall Mouth and Throat Soreness This was scored from 0=no soreness to 10=worst possible soreness.</description>
        <time_frame>28 days</time_frame>
        <population>Intention to treat(ITT) OMDQ AUC over time. Not all patients reported data from OMDQ therefore there is lower number of patients in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Mucositis Daily Questionnaire (OMDQ)</title>
          <description>OMDQ (Oral Mucositis Daily Questionnaire) scale was used to measure Overall Mouth and Throat Soreness This was scored from 0=no soreness to 10=worst possible soreness.</description>
          <population>Intention to treat(ITT) OMDQ AUC over time. Not all patients reported data from OMDQ therefore there is lower number of patients in this analysis.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.59" spread="1.619"/>
                    <measurement group_id="O2" value="2.64" spread="1.539"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oral Mucositis Assessment Scale (OMAS)</title>
        <description>Summary of Oral Mucositis Assessment Scale (OMAS) Ulceration and Erythema Scores Extent of ulceration (grade 0-3) and severity of erythema (grade 0-2) according to the OMAS (Oral Mucositis Assessment Scale) assessed by a dental practitioner twice-weekly over the 28-day study period.&#xD;
The extent of ulceration was rated as follows:&#xD;
0 no lesion&#xD;
1 cm2&#xD;
1-3 cm2&#xD;
&gt;3 cm2&#xD;
The severity of erythema was assessed as follows:&#xD;
0 none&#xD;
not severe&#xD;
severe</description>
        <time_frame>28 days</time_frame>
        <population>Intention to treat (ITT) Ulceration and Erythema.OMAS was only performed in sites were a dentist was available therefore lower numbers in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Mucositis Assessment Scale (OMAS)</title>
          <description>Summary of Oral Mucositis Assessment Scale (OMAS) Ulceration and Erythema Scores Extent of ulceration (grade 0-3) and severity of erythema (grade 0-2) according to the OMAS (Oral Mucositis Assessment Scale) assessed by a dental practitioner twice-weekly over the 28-day study period.&#xD;
The extent of ulceration was rated as follows:&#xD;
0 no lesion&#xD;
1 cm2&#xD;
1-3 cm2&#xD;
&gt;3 cm2&#xD;
The severity of erythema was assessed as follows:&#xD;
0 none&#xD;
not severe&#xD;
severe</description>
          <population>Intention to treat (ITT) Ulceration and Erythema.OMAS was only performed in sites were a dentist was available therefore lower numbers in the analysis.</population>
          <units>score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ulceration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0.21"/>
                    <measurement group_id="O2" value="0" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="0.70"/>
                    <measurement group_id="O2" value="0.5" spread="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital Stay, Days</title>
        <description>Duration of hospital stay (time from admission to discharge)</description>
        <time_frame>28 days</time_frame>
        <population>Intention to treat (ITT) Hospital stay, days</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital Stay, Days</title>
          <description>Duration of hospital stay (time from admission to discharge)</description>
          <population>Intention to treat (ITT) Hospital stay, days</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.7" spread="4.45"/>
                    <measurement group_id="O2" value="24.5" spread="3.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population</title>
        <description>Summary of WHO (World Health Organisation) Oral Toxicity Scores AUC Over the 28-Day Period Per protocol population.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
        <time_frame>28 days</time_frame>
        <population>Per Protocol (PP) without Last observation carried over(LOCF)</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population</title>
          <description>Summary of WHO (World Health Organisation) Oral Toxicity Scores AUC Over the 28-Day Period Per protocol population.&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
          <population>Per Protocol (PP) without Last observation carried over(LOCF)</population>
          <units>score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.39" spread="0.402"/>
                    <measurement group_id="O2" value="0.56" spread="0.587"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurence of Oral Mucositis, Per Protocol Population</title>
        <description>Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organisation) oral toxicity scale grade 0-4&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
        <time_frame>28 days</time_frame>
        <population>Per Protocol (PP)</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Occurence of Oral Mucositis, Per Protocol Population</title>
          <description>Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organisation) oral toxicity scale grade 0-4&#xD;
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
          <population>Per Protocol (PP)</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Oral Mucositis, Per Protocol Population</title>
        <description>Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis is graded according to the 5-point oral mucositis WHO scale Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
        <time_frame>28 days</time_frame>
        <population>Per Protocol (PP). There were 9 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis</population>
        <group_list>
          <group group_id="O1">
            <title>Standard-Of-Care + Episil(R)</title>
            <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
          <group group_id="O2">
            <title>Standard-Of-Care</title>
            <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Oral Mucositis, Per Protocol Population</title>
          <description>Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis is graded according to the 5-point oral mucositis WHO scale Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible</description>
          <population>Per Protocol (PP). There were 9 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="5.85"/>
                    <measurement group_id="O2" value="10.1" spread="5.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Standard-Of-Care + Episil(R)</title>
          <description>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed&#xD;
episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
        </group>
        <group group_id="E2">
          <title>Standard-Of-Care</title>
          <description>Oral hygiene procedures&#xD;
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 14.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonay haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 14.0</default_vocab>
        <default_assessment>Non-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="26" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="57"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>febrile neutropenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="57"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="57"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="57"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="57"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="52"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Håkan Olsson DDS, PhD</name_or_title>
      <organization>Camurus AB</organization>
      <phone>+46 46 2863852</phone>
      <email>Hakan.Olsson@camurus.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/NCT01684566
org study id: HS-10-396
nct id: NCT01684566
lead sponsor: 
has dmc: No
To compare the performance of standard of care (SOC) + episil® versus SOC alone on oral
      mucositis in patients receiving conditioning treatment for hematopoietic stem cell
      transplantation (HSCT). The primary variable will be the area under the curve (AUC) of oral
      mucositis scores defined by the World Health Organisation (WHO) oral toxicity scale assessed
      daily by the investigator over the 28-day study period.
This was multicentre, open-label, randomised parallel-group study. Patients were randomised
      to one of two parallel treatment groups: episil® in combination with SOC or SOC alone.

      The study was originally planned to be conducted in several sites in the following countries:
      Denmark, Israel, Poland, and Sweden. Following a country-specific Amendment on 20-Feb-2013
      and a German Ethical Committee (EC) approval in 07-May-2013, Germany was added to the list of
      countries where the study would be conducted. No study sites were initiated in Denmark.

      The study design was aimed to facilitate direct comparison of the performance of SOC +
      episil® versus SOC alone. The study was conducted in an open-label manner that is common in
      trials involving cancer patients, as this takes into the account the ethical issues involved
      in this indication and patient population. To reduce the likelihood of bias, assignment to
      study treatment was randomised.

      SOC as control group is appropriate and widely used, especially in trials involving cancer
      patients. In this particular study, basic oral hygiene consisting of brushing, flossing,
      rinsing and moisturising was taken as the SOC used as control group.

      .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population
time frame: 28 days
description: Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations.
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible
measure: WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population
time frame: 28 days
description: Summary of WHO (World Health Organisation) Oral Toxicity Scores AUC Over the 28-Day Period Per protocol population.
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible
measure: Occurrence of Oral Mucositis
time frame: 28 days
description: Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organization) oral toxicity scale grade 0-4.
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible
measure: Duration of Oral Mucositis, Intention to Treat Population
time frame: 28 days
description: Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis was graded according to WHO 5 Point grading scale on a daily basis.
Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible
measure: Oral Mucositis Daily Questionnaire (OMDQ)
time frame: 28 days
description: OMDQ (Oral Mucositis Daily Questionnaire) scale was used to measure Overall Mouth and Throat Soreness This was scored from 0=no soreness to 10=worst possible soreness.
measure: Oral Mucositis Assessment Scale (OMAS)
time frame: 28 days
description: Summary of Oral Mucositis Assessment Scale (OMAS) Ulceration and Erythema Scores Extent of ulceration (grade 0-3) and severity of erythema (grade 0-2) according to the OMAS (Oral Mucositis Assessment Scale) assessed by a dental practitioner twice-weekly over the 28-day study period.
The extent of ulceration was rated as follows:
0 no lesion
1 cm2
1-3 cm2
>3 cm2
The severity of erythema was assessed as follows:
0 none
not severe
severe
measure: Hospital Stay, Days
time frame: 28 days
description: Duration of hospital stay (time from admission to discharge)
measure: Occurence of Oral Mucositis, Per Protocol Population
time frame: 28 days
description: Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organisation) oral toxicity scale grade 0-4
A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible
measure: Duration of Oral Mucositis, Per Protocol Population
time frame: 28 days
description: Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis is graded according to the 5-point oral mucositis WHO scale Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible
arm group label: Standard-Of-Care + episil(R)
arm group type: Experimental
description: Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed
arm group label: Standard-Of-Care
arm group type: Other
description: Oral hygiene procedures
intervention type: Device
intervention name: episil(R)
description: episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.
arm group label: Standard-Of-Care + episil(R)
intervention type: Other
intervention name: Oral hygiene procedures
description: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
arm group label: Standard-Of-Care
arm group label: Standard-Of-Care + episil(R)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Karin Garming-Legert, DDS, PhD.
role: Principal Investigator
affiliation: Karolinska Institutet, Stockholm, Sweden
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Israel
country: Poland
country: Sweden
responsible party type: Sponsor
mesh term: Mucositis
mesh term: Stomatitis
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 