<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/NCT04432376</url>
  </required_header>
  <id_info>
    <org_study_id>MZ-0120-ESP3-052</org_study_id>
    <nct_id>NCT04432376</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Miconazole Oil Versus Vehicle on Fungal Infection of the Ear Canal (Otomycosis)</brief_title>
  <official_title>Randomized, Double-blind, Phase III Study of the Efficacy and Safety of Miconazole Oil Versus Vehicle Oil in the Treatment of Otomycosis, Followed by an Open-label Safety Evaluation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hill Dermaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Abond CRO Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hill Dermaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study involves two portions, a randomized, double-blind portion and an open-label&#xD;
      portion, to evaluate the efficacy and safety of Miconazole oil 2% versus its Vehicle in the&#xD;
      treatment of fungal infection of the outer ear canal (Otomycosis). The subjects randomized in&#xD;
      the first portion of the study will have active fungal infection of the ear(s) and will be&#xD;
      treated with either Miconazole Oil or the Vehicle for 14 days twice daily, 5 drops into the&#xD;
      affected ear(s) per dose. The subjects enrolled in the open-label portion of the study may or&#xD;
      may not have active fungal infection of the ear(s), and will be given the Miconazole Oil&#xD;
      active drug following the same application of 5 drops into the ear(s) twice daily for 14&#xD;
      days.&#xD;
&#xD;
      The intention of the study is to evaluate the efficacy of Miconazole Oil on fungal infection&#xD;
      of the ears when applied using 5 drops into the ear(s) twice daily for 14 days continuously.&#xD;
      This study also intends to show safety of Miconazole Oil 5 drops into each ear twice a day&#xD;
      for 14 consecutive days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be conducted in 2 portions:&#xD;
&#xD;
        1. Enrollment A, which will consist of 2 treatment periods as follows and will be conducted&#xD;
           in subjects with otomycosis:&#xD;
&#xD;
             1. A randomized, double-blind, parallel-group treatment period. This treatment period&#xD;
                will be referred to as the &quot;Randomization Period&quot; and will be followed by:&#xD;
&#xD;
             2. An optional, open-label treatment period with miconazole oil. This treatment period&#xD;
                will be referred to as the &quot;Optional Open-label Extension.&quot;&#xD;
&#xD;
        2. Enrollment B will consist of open-label treatment with miconazole oil in subjects who&#xD;
           will not be required to have signs and symptoms of otomycosis.&#xD;
&#xD;
      The study will start with Enrollment A, with an estimated 220 male or female subjects with&#xD;
      otomycosis. Subjects will be randomly assigned in a 1:1 ratio to receive miconazole oil or&#xD;
      vehicle (placebo), for 14 days. The study drug will be administered as 5 drops per ear at ~30&#xD;
      mg per drop instilled into the external ear canal of the ear(s) affected by otomycosis.&#xD;
&#xD;
      In the Randomization Period, both the subject and the investigator and study staff are&#xD;
      blinded to the contents of the study drug.&#xD;
&#xD;
      At Screening/Baseline (Day 1), assessment of the signs and symptoms of otomycosis (pruritus,&#xD;
      debris, visual examination for presence of fungal elements, and aural fullness), evaluation&#xD;
      of medical history, pregnancy screening in female of childbearing potential, and, prior and&#xD;
      concomitant medications, will be collected. Subjects with positive signs and symptoms of&#xD;
      otomycosis and who meet all eligibility criteria will enter the study. Fungal culture of&#xD;
      affected ear(s) will be taken, debris will be cleaned from the affected ear(s), and subject&#xD;
      will be randomized and study drug dispensed. Treatment will be for 14 days. Day 8 On&#xD;
      Treatment Visit will include clinical evaluation of otomycosis, cleaning of ear(s), and&#xD;
      assessment of Adverse Events (AEs) and concomitant medications, and continue treatment up to&#xD;
      Day 14. Day 15 End of Treatment Visit will include clinical evaluation of otomycosis and&#xD;
      fungal culture, adverse events including Treatment emergent adverse events (TEAEs) and&#xD;
      concomitant medications assessed. Day 22 Test of Cure Visit is an assessment of clinical&#xD;
      signs and symptoms of otomycosis and fungal culture, AEs and concomitant medications&#xD;
      assessed, and urine pregnancy test performed in women of childbearing potential.&#xD;
&#xD;
      Only the subjects that had positive fungal (mycological) culture at Baseline will be&#xD;
      evaluated for efficacy. This is the Modified intent-to-treat (MITT) population.&#xD;
&#xD;
      The Optional Open-label Extension period will allow subjects to get miconazole oil for 14&#xD;
      days. No unblinding of the subject's treatment in the Randomization Period will occur at this&#xD;
      time.&#xD;
&#xD;
      For Enrollment B, male or female subjects will be enrolled to receive miconazole oil to use&#xD;
      for 14 days and will be evaluated for safety.&#xD;
&#xD;
      Intent-to-Treat (ITT) population are all subjects enrolled and randomized to treatment.&#xD;
      Modified Intent-to-Treat (MITT) population are subjects in the ITT population with a clinical&#xD;
      diagnosis of otomycosis confirmed by positive fungal culture at Baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Actual">November 1, 2021</completion_date>
  <primary_completion_date type="Actual">November 1, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Two phases; initial is randomized double-blind active vs placebo on a pre-determined number of subjects with otomycosis, to finish before starting second phase. Second phase is open-label use on diseased or healthy subjects to evaluate safety. Subjects from initial phase may crossover to second phase open-label if they meet the requirements, and new diseased or healthy subjects meeting requirements may enroll in this open-label phase.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Clinical Investigators, study staff and subjects randomized to the initial phase of the study are blinded to active drug and placebo.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Subjects With Therapeutic Cure</measure>
    <time_frame>21 days from first day of drug application</time_frame>
    <description>&quot;therapeutic cure&quot; is &quot;mycological cure&quot; plus &quot;clinical cure, in the Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).&#xD;
Mycological cure is a negative mycological culture (culture is either positive or negative). Score=0 is best.&#xD;
Clinical cure is absence of all otomycosis signs and symptoms (s/s) of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Mycological Cure</measure>
    <time_frame>21 days from first day of drug application</time_frame>
    <description>Mycological cure is a negative mycological culture for the study ear at test of cure visit, in Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
Grading is based on positive or negative mycological (fungal) culture. Negative culture is required.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.&#xD;
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Clinical Cure</measure>
    <time_frame>21 days from first day of drug application</time_frame>
    <description>Absence of all otomycosis signs and symptoms according to the scales for each individual sign/symptom. Score=0 is best.&#xD;
Clinical cure is absence of all otomycosis signs and symptoms of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
ITT (intent to treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">382</enrollment>
  <condition>Otomycosis</condition>
  <arm_group>
    <arm_group_label>Active treatment arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment with miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo treatment arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Treatment with the vehicle oil, placebo, 5 drops into each ear twice daily for 14 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open-label treatment arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Application of miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>miconazole 2% oil</intervention_name>
    <description>Drug treatment of otomycosis for 14 days</description>
    <arm_group_label>Active treatment arm</arm_group_label>
    <arm_group_label>Open-label treatment arm</arm_group_label>
    <other_name>active treatment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vehicle oil</intervention_name>
    <description>Placebo treatment of otomycosis for 14 days</description>
    <arm_group_label>Placebo treatment arm</arm_group_label>
    <other_name>placebo treatment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Randomized blinded initial phase of study:&#xD;
&#xD;
          -  Male or non-pregnant, non-lactating females with a clinical diagnosis of uncomplicated&#xD;
             otomycosis of the external ear only,&#xD;
&#xD;
          -  Intact tympanic membrane in the ear(s) to be treated with study drug,&#xD;
&#xD;
          -  In general good health as determined by medical examination and medical history,&#xD;
&#xD;
          -  Free of clinically significant disease, including diabetes mellitus, that is not&#xD;
             well-controlled or that could interfere with the study.&#xD;
&#xD;
        Open-label second phase of study:&#xD;
&#xD;
          -  Male or non-pregnant, non-lactating females with an intact tympanic membrane in the&#xD;
             ear(s) to be treated with study drug,&#xD;
&#xD;
          -  In general good health as determined by medical examination and medical history,&#xD;
&#xD;
          -  Free of clinically significant disease, including diabetes mellitus, that is not&#xD;
             well-controlled or that could interfere with the study.&#xD;
&#xD;
        Exclusion Criteria::&#xD;
&#xD;
          -  Presence of dermatoses or conditions of the ear that may interfere with evaluation of&#xD;
             otomycosis or with safety evaluations, including concomitant otic infections that&#xD;
             require antimicrobial treatment,&#xD;
&#xD;
          -  Disease that has spread beyond the external ear(s), or pre-existing skin atrophy of&#xD;
             the affected ear(s);&#xD;
&#xD;
          -  Tympanostomy tube or perforated tympanic membrane;&#xD;
&#xD;
          -  History of prior surgery directly affecting and compromising the external auditory&#xD;
             canal and/or tympanic membrane, except for prior tympanostomy tube(s) that have&#xD;
             already been removed and completely healed;&#xD;
&#xD;
          -  Use of any topical medicated treatments for otomycosis within 14 days of study entry;&#xD;
&#xD;
          -  Use of any systemic antifungal therapy within 28 days of study entry, warfarin within&#xD;
             28 days of study entry, immunosuppressive or immune-stimulating drugs within 28 days&#xD;
             of study entry, or systemic steroids within 3 months of study entry;&#xD;
&#xD;
          -  Fever of ≥100°F at study entry;&#xD;
&#xD;
          -  Otomycosis that has been unresponsive to previous antifungal treatment;&#xD;
&#xD;
          -  Known hypersensitivity to any of the components in the test formulation;&#xD;
&#xD;
          -  Participation in another investigative trial within 28 days of study entry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arnaldo Rivera, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri-Columbia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Quyen T Nguyen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSD</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kenneth Hodge, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Advanced ENT and Allergy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Patrick Dennis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>DelRicht Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sammy Vaught, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lake ENT &amp; FPS</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Timothy Fitzgibbon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OnSite Clinical Solutions</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Ansley, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Carolina ENT</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Randall Ow, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>DaVinci Research LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Oscar DeValle, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West Houston Clinical Research Service</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Linda Woo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Head and Neck Surgery Specialists</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brent Benscoter, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sacramento ENT / DaVinci Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeffrey Adelglass, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Your Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gary Brandt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Delricht</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Head and Neck Surgery Specialists</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSD</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DaVinci Research, LLC</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sacramento ENT / DaVinci Research</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake ENT &amp; FPS</name>
      <address>
        <city>Leesburg</city>
        <state>Florida</state>
        <zip>34748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced ENT &amp; Allergy</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DelRicht Research</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Missouri</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OnSite Clinical Solutions</name>
      <address>
        <city>Dillon</city>
        <state>South Carolina</state>
        <zip>29536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina ENT</name>
      <address>
        <city>Orangeburg</city>
        <state>South Carolina</state>
        <zip>29118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Houston Clinical Research Services</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Your Health</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <results_first_submitted>September 8, 2022</results_first_submitted>
  <results_first_submitted_qc>October 7, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 4, 2022</results_first_posted>
  <last_update_submitted>October 7, 2022</last_update_submitted>
  <last_update_submitted_qc>October 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Otomycosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Miconazole</mesh_term>
  </intervention_browse>
  <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>September 14, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/76/NCT04432376/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active Treatment Arm</title>
          <description>Participants randomized to Active Treatment with miconazole 2% oil, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
        </group>
        <group group_id="P2">
          <title>Placebo Treatment Arm</title>
          <description>Participants randomized to Placebo Treatment (with vehicle oil placebo), 5 drops into affected ear twice daily for 14 consecutive days&#xD;
vehicle oil: Placebo treatment of otomycosis for 14 days</description>
        </group>
        <group group_id="P3">
          <title>Open-label Application Group</title>
          <description>Application of miconazole 2% oil, 5 drops into each ear or the affected ear, twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug application for 14 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-blind Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="89"/>
                <participants group_id="P2" count="90"/>
                <participants group_id="P3" count="0">Open-label treatment group started under Period 2. Not applicable for Period 1.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="84"/>
                <participants group_id="P2" count="79"/>
                <participants group_id="P3" count="0">Open-label treatment group started under Period 2. Not applicable for Period 1.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>subject enrolled in the Optional Open Label arm</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Enrollment B, Open Label Safety Group.</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0">Participants randomized to Active-treatment included in Period 1 only, double-blind randomized period.</participants>
                <participants group_id="P2" count="0">Participants randomized to Placebo-treatment included in Period 1 only, double-blind randomized period.</participants>
                <participants group_id="P3" count="203">Participants/subjects enrolled in open-label treatment arm were not required to have otomycosis, hence were not assessed for efficacy and not included in Period 1. This population was Not randomized, assessed only for safety, and included in Period 2 only.</participants>
              </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="203"/>
              </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_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-Treat (ITT) population - subjects enrolled and randomized according to treatment group.</population>
      <group_list>
        <group group_id="B1">
          <title>Active Treatment Arm</title>
          <description>Treatment with miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
        </group>
        <group group_id="B2">
          <title>Placebo Treatment Arm</title>
          <description>Treatment with the vehicle oil, placebo, 5 drops into each ear twice daily for 14 consecutive days&#xD;
vehicle oil: Placebo treatment of otomycosis for 14 days</description>
        </group>
        <group group_id="B3">
          <title>Open-label Treatment Arm</title>
          <description>Application of miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</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="89"/>
            <count group_id="B2" value="90"/>
            <count group_id="B3" value="203"/>
            <count group_id="B4" value="382"/>
          </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="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="178"/>
                    <measurement group_id="B4" value="295"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="70"/>
                  </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="38"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="142"/>
                    <measurement group_id="B4" value="224"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="38"/>
                    <measurement group_id="B4" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="165"/>
                    <measurement group_id="B4" value="302"/>
                  </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>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="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="14"/>
                  </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="7"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="49"/>
                    <measurement group_id="B4" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="133"/>
                    <measurement group_id="B4" value="277"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="22"/>
                  </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>Mycological culture</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>positive culture</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="131"/>
                  </measurement_list>
                </category>
                <category>
                  <title>negative culture</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not cultured</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="203"/>
                    <measurement group_id="B4" value="203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Otomycosis signs/symptoms - Pruritus</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>none</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>mild</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>moderate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="114"/>
                  </measurement_list>
                </category>
                <category>
                  <title>severe</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not assessed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="203"/>
                    <measurement group_id="B4" value="203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Otomycosis signs/symptoms - Debris</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>none</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>scant</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>moderate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="103"/>
                  </measurement_list>
                </category>
                <category>
                  <title>heavy</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not assessed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="203"/>
                    <measurement group_id="B4" value="203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Otomycosis signs/symptoms - Fungal elements</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>present</title>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="179"/>
                  </measurement_list>
                </category>
                <category>
                  <title>absent</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>not assessed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="203"/>
                    <measurement group_id="B4" value="203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Otomycosis signs/symptoms - Aural fullness</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>none</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>mild</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>moderate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>severe</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>not assessed</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="203"/>
                    <measurement group_id="B4" value="203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects With Therapeutic Cure</title>
        <description>&quot;therapeutic cure&quot; is &quot;mycological cure&quot; plus &quot;clinical cure, in the Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).&#xD;
Mycological cure is a negative mycological culture (culture is either positive or negative). Score=0 is best.&#xD;
Clinical cure is absence of all otomycosis signs and symptoms (s/s) of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.</description>
        <time_frame>21 days from first day of drug application</time_frame>
        <population>MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT (intent-to-treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</population>
        <group_list>
          <group group_id="O1">
            <title>Active Treatment Arm</title>
            <description>Treatment with miconazole 2% oil, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo Treatment Arm</title>
            <description>Treatment with the vehicle oil, placebo, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
vehicle oil: Placebo treatment of otomycosis for 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Therapeutic Cure</title>
          <description>&quot;therapeutic cure&quot; is &quot;mycological cure&quot; plus &quot;clinical cure, in the Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).&#xD;
Mycological cure is a negative mycological culture (culture is either positive or negative). Score=0 is best.&#xD;
Clinical cure is absence of all otomycosis signs and symptoms (s/s) of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.</description>
          <population>MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT (intent-to-treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</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="67"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Achieved Therapeutic cure (Score=0 fungal culture and clinical signs,symptoms)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Achieve Therapeutic cure (Positive fungal culture AND/OR clinical score 1 or greater each s/s</title>
                  <measurement_list>
                    <measurement group_id="O1" value="53"/>
                    <measurement group_id="O2" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Mycological Cure</title>
        <description>Mycological cure is a negative mycological culture for the study ear at test of cure visit, in Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
Grading is based on positive or negative mycological (fungal) culture. Negative culture is required.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.&#xD;
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</description>
        <time_frame>21 days from first day of drug application</time_frame>
        <population>MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</population>
        <group_list>
          <group group_id="O1">
            <title>Active Treatment Arm</title>
            <description>Treatment with miconazole 2% oil, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo Treatment Arm</title>
            <description>Treatment with the vehicle oil, placebo, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
vehicle oil: Placebo treatment of otomycosis for 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Mycological Cure</title>
          <description>Mycological cure is a negative mycological culture for the study ear at test of cure visit, in Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
Grading is based on positive or negative mycological (fungal) culture. Negative culture is required.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.&#xD;
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</description>
          <population>MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</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="67"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Achieved mycological cure (negative fungal culture)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not achieved mycological cure (positive fungal culture)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Clinical Cure</title>
        <description>Absence of all otomycosis signs and symptoms according to the scales for each individual sign/symptom. Score=0 is best.&#xD;
Clinical cure is absence of all otomycosis signs and symptoms of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
ITT (intent to treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</description>
        <time_frame>21 days from first day of drug application</time_frame>
        <population>MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</population>
        <group_list>
          <group group_id="O1">
            <title>Active Treatment Arm</title>
            <description>Treatment with miconazole 2% oil, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo Treatment Arm</title>
            <description>Treatment with the vehicle oil, placebo, 5 drops into affected ear twice daily for 14 consecutive days&#xD;
vehicle oil: Placebo treatment of otomycosis for 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Clinical Cure</title>
          <description>Absence of all otomycosis signs and symptoms according to the scales for each individual sign/symptom. Score=0 is best.&#xD;
Clinical cure is absence of all otomycosis signs and symptoms of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.&#xD;
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.&#xD;
ITT (intent to treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</description>
          <population>MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).</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="67"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Achieved clinical cure (score = 0 for all signs, symptoms)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not achieved clinical cure (score equal to or greater than 1 for each sign, symptom).</title>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                    <measurement group_id="O2" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AEs) are collected at the start and during use of study drug, Day 1 to Day 14 of study drug application. Collection of adverse events start the day the patient first applied the study drug and end the day of the patient's last study visit, Day 21. Adverse events were monitored through study completion.</time_frame>
      <desc>Treatment-emergent adverse events (TEAEs) are those with an onset on or after the date of first study drug application, up to the last application day for each patient. Adverse events were monitored through study completion.</desc>
      <group_list>
        <group group_id="E1">
          <title>Active Treatment Arm</title>
          <description>Treatment with miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
        </group>
        <group group_id="E2">
          <title>Placebo Treatment Arm</title>
          <description>Treatment with the vehicle oil, placebo, 5 drops into each ear twice daily for 14 consecutive days&#xD;
vehicle oil: Placebo treatment of otomycosis for 14 days</description>
        </group>
        <group group_id="E3">
          <title>Open-label Treatment Arm</title>
          <description>Application of miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days&#xD;
miconazole 2% oil: Drug treatment of otomycosis for 14 days</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</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="89"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>acute kidney injury</sub_title>
                <description>Acute kidney injury on Chronic Kidney Disease (CKD)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>hypotension</sub_title>
                <description>Hypotension</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1.1</frequency_threshold>
        <default_vocab>MedDRA 23.0</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="41" subjects_at_risk="89"/>
                <counts group_id="E2" subjects_affected="51" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>ear discomfort</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="89"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>vertigo</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>tympanic membrane perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>application site irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>application site pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="89"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>application site pruritus</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="89"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="90"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>ear infection fungal</sub_title>
                <counts group_id="E1" events="27" subjects_affected="27" subjects_at_risk="89"/>
                <counts group_id="E2" events="33" subjects_affected="33" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>otitis externa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>otitis externa bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>otitis externa fungal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>tooth abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>exposure to SARS-CoV-2</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>hypovolemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>paranasal cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>rhinitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="89"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="203"/>
              </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>Proprietary Information will need prior written consent of the sponsor. PI will hold in confidence and not disclose any Proprietary Information unless disclosure has its prior written consent from sponsor, or that the information is disclosed to personnel who need to know. Sponsor will not prohibit PI to comply with applicable laws and regulations, provided PI gives prior written notice to Sponsor. Disclosure allowed if legally required and accorded confidential treatment.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The limited number of patients with otomycosis at any one time, and the lack of standardized FDA-approved clinical studies on otomycosis have proven to be challenging and difficult to assign predetermined analysis endpoints. This is in line with the challenges described in the FDA Accelerating Rare disease Cures Program, such as challenges faced when using well-established trial designs, and complexities in endpoint selection when there is limited information or understanding of the disease.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Rosario G Ramirez, Medical Director</name_or_title>
      <organization>Hill Dermaceuticals</organization>
      <phone>4073231887</phone>
      <email>nini.ramirez@hillderm.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/NCT04432376
org study id: MZ-0120-ESP3-052
nct id: NCT04432376
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study involves two portions, a randomized, double-blind portion and an open-label
      portion, to evaluate the efficacy and safety of Miconazole oil 2% versus its Vehicle in the
      treatment of fungal infection of the outer ear canal (Otomycosis). The subjects randomized in
      the first portion of the study will have active fungal infection of the ear(s) and will be
      treated with either Miconazole Oil or the Vehicle for 14 days twice daily, 5 drops into the
      affected ear(s) per dose. The subjects enrolled in the open-label portion of the study may or
      may not have active fungal infection of the ear(s), and will be given the Miconazole Oil
      active drug following the same application of 5 drops into the ear(s) twice daily for 14
      days.

      The intention of the study is to evaluate the efficacy of Miconazole Oil on fungal infection
      of the ears when applied using 5 drops into the ear(s) twice daily for 14 days continuously.
      This study also intends to show safety of Miconazole Oil 5 drops into each ear twice a day
      for 14 consecutive days.
This study will be conducted in 2 portions:

        1. Enrollment A, which will consist of 2 treatment periods as follows and will be conducted
           in subjects with otomycosis:

             1. A randomized, double-blind, parallel-group treatment period. This treatment period
                will be referred to as the "Randomization Period" and will be followed by:

             2. An optional, open-label treatment period with miconazole oil. This treatment period
                will be referred to as the "Optional Open-label Extension."

        2. Enrollment B will consist of open-label treatment with miconazole oil in subjects who
           will not be required to have signs and symptoms of otomycosis.

      The study will start with Enrollment A, with an estimated 220 male or female subjects with
      otomycosis. Subjects will be randomly assigned in a 1:1 ratio to receive miconazole oil or
      vehicle (placebo), for 14 days. The study drug will be administered as 5 drops per ear at ~30
      mg per drop instilled into the external ear canal of the ear(s) affected by otomycosis.

      In the Randomization Period, both the subject and the investigator and study staff are
      blinded to the contents of the study drug.

      At Screening/Baseline (Day 1), assessment of the signs and symptoms of otomycosis (pruritus,
      debris, visual examination for presence of fungal elements, and aural fullness), evaluation
      of medical history, pregnancy screening in female of childbearing potential, and, prior and
      concomitant medications, will be collected. Subjects with positive signs and symptoms of
      otomycosis and who meet all eligibility criteria will enter the study. Fungal culture of
      affected ear(s) will be taken, debris will be cleaned from the affected ear(s), and subject
      will be randomized and study drug dispensed. Treatment will be for 14 days. Day 8 On
      Treatment Visit will include clinical evaluation of otomycosis, cleaning of ear(s), and
      assessment of Adverse Events (AEs) and concomitant medications, and continue treatment up to
      Day 14. Day 15 End of Treatment Visit will include clinical evaluation of otomycosis and
      fungal culture, adverse events including Treatment emergent adverse events (TEAEs) and
      concomitant medications assessed. Day 22 Test of Cure Visit is an assessment of clinical
      signs and symptoms of otomycosis and fungal culture, AEs and concomitant medications
      assessed, and urine pregnancy test performed in women of childbearing potential.

      Only the subjects that had positive fungal (mycological) culture at Baseline will be
      evaluated for efficacy. This is the Modified intent-to-treat (MITT) population.

      The Optional Open-label Extension period will allow subjects to get miconazole oil for 14
      days. No unblinding of the subject's treatment in the Randomization Period will occur at this
      time.

      For Enrollment B, male or female subjects will be enrolled to receive miconazole oil to use
      for 14 days and will be evaluated for safety.

      Intent-to-Treat (ITT) population are all subjects enrolled and randomized to treatment.
      Modified Intent-to-Treat (MITT) population are subjects in the ITT population with a clinical
      diagnosis of otomycosis confirmed by positive fungal culture at Baseline.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Two phases; initial is randomized double-blind active vs placebo on a pre-determined number of subjects with otomycosis, to finish before starting second phase. Second phase is open-label use on diseased or healthy subjects to evaluate safety. Subjects from initial phase may crossover to second phase open-label if they meet the requirements, and new diseased or healthy subjects meeting requirements may enroll in this open-label phase.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Clinical Investigators, study staff and subjects randomized to the initial phase of the study are blinded to active drug and placebo.
measure: Percentage of Subjects With Therapeutic Cure
time frame: 21 days from first day of drug application
description: "therapeutic cure" is "mycological cure" plus "clinical cure, in the Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Fungal culture results verified as (+) or (-) after enrollment.
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).
Mycological cure is a negative mycological culture (culture is either positive or negative). Score=0 is best.
Clinical cure is absence of all otomycosis signs and symptoms (s/s) of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.
measure: Percentage of Subjects With Mycological Cure
time frame: 21 days from first day of drug application
description: Mycological cure is a negative mycological culture for the study ear at test of cure visit, in Modified intent to treat (MITT) only: patients with + fungal culture at baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.
Grading is based on positive or negative mycological (fungal) culture. Negative culture is required.
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline.
Intent to treat (ITT) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).
measure: Percentage of Subjects With Clinical Cure
time frame: 21 days from first day of drug application
description: Absence of all otomycosis signs and symptoms according to the scales for each individual sign/symptom. Score=0 is best.
Clinical cure is absence of all otomycosis signs and symptoms of Pruritus, Debris, and Aural fullness, graded as (scores) 0=none, 1=mild, 2=moderate, 3=severe; and Presence of fungal elements, score 0=No fungal elements, 1=fungal elements present on visual inspection. Score=0 is best.
Efficacy analysis was performed only on MITT (modified intent-to-treat) population, consisting of only those patients that had positive fungal culture at Baseline. Subjects that had negative fungal culture at Baseline were not included in MITT. Fungal culture results verified as (+) or (-) after enrollment.
ITT (intent to treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).
arm group label: Active treatment arm
arm group type: Active Comparator
description: Treatment with miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days
arm group label: Placebo treatment arm
arm group type: Placebo Comparator
description: Treatment with the vehicle oil, placebo, 5 drops into each ear twice daily for 14 consecutive days
arm group label: Open-label treatment arm
arm group type: Other
description: Application of miconazole 2% oil, 5 drops into each ear twice daily for 14 consecutive days
intervention type: Drug
intervention name: miconazole 2% oil
description: Drug treatment of otomycosis for 14 days
arm group label: Active treatment arm
arm group label: Open-label treatment arm
other name: active treatment
intervention type: Drug
intervention name: vehicle oil
description: Placebo treatment of otomycosis for 14 days
arm group label: Placebo treatment arm
other name: placebo treatment
criteria: 
gender: All
minimum age: 7 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Arnaldo Rivera, MD
role: Principal Investigator
affiliation: University of Missouri-Columbia
last name: Quyen T Nguyen, MD
role: Principal Investigator
affiliation: UCSD
last name: Kenneth Hodge, MD
role: Principal Investigator
affiliation: Advanced ENT and Allergy
last name: Patrick Dennis, MD
role: Principal Investigator
affiliation: DelRicht Research
last name: Sammy Vaught, MD
role: Principal Investigator
affiliation: Lake ENT & FPS
last name: Timothy Fitzgibbon, MD
role: Principal Investigator
affiliation: OnSite Clinical Solutions
last name: John Ansley, MD
role: Principal Investigator
affiliation: Carolina ENT
last name: Randall Ow, MD
role: Principal Investigator
affiliation: DaVinci Research LLC
last name: Oscar DeValle, MD
role: Principal Investigator
affiliation: West Houston Clinical Research Service
last name: Linda Woo, MD
role: Principal Investigator
affiliation: Head and Neck Surgery Specialists
last name: Brent Benscoter, MD
role: Principal Investigator
affiliation: Sacramento ENT / DaVinci Research
last name: Jeffrey Adelglass, MD
role: Principal Investigator
affiliation: Research Your Health
last name: Gary Brandt, MD
role: Principal Investigator
affiliation: Delricht
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country: United States
responsible party type: Sponsor
mesh term: Otomycosis
mesh term: Miconazole
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The limited number of patients with otomycosis at any one time, and the lack of standardized FDA-approved clinical studies on otomycosis have proven to be challenging and difficult to assign predetermined analysis endpoints. This is in line with the challenges described in the FDA Accelerating Rare disease Cures Program, such as challenges faced when using well-established trial designs, and complexities in endpoint selection when there is limited information or understanding of the disease.
point of contact: 