<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/NCT03018691</url>
  </required_header>
  <id_info>
    <org_study_id>271-102-00002</org_study_id>
    <secondary_id>JapicCTI-173484</secondary_id>
    <nct_id>NCT03018691</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Vehicle-controlled, Parallel-group Trial to Assess the Safety and Efficacy of 0.3% and 1% OPA-15406 Ointments When Administered for 4 Weeks in Pediatric Patients With Atopic Dermatitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Otsuka Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety, efficacy (dose response) and pharmacokinetics of 0.3% and 1%&#xD;
      OPA-15406 when applied twice daily for 4 weeks in pediatric patients with atopic dermatitis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Number of Subjects Experiencing AEs</measure>
    <time_frame>Week 0-4</time_frame>
    <description>The number of subjects experiencing AEs will be calculated for each treatment group.&#xD;
Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4</measure>
    <time_frame>Baseline and Week 4</time_frame>
    <description>The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Eczema Area and Severity Index (EASI) Score</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score</measure>
    <time_frame>Baseline, Hour 156</time_frame>
    <description>The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary.&#xD;
0 : None&#xD;
: Mild&#xD;
: Moderate&#xD;
: Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Percentage Affected Body Surface Area</measure>
    <time_frame>Baseline, Week 8, 16, 24</time_frame>
    <description>The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA. The negative value showed the degree of improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean (SD) OPA-15406 Plasma Trough Concentrations at week1</measure>
    <time_frame>Week 1</time_frame>
    <description>The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean (SD) OPA-15406 Plasma Trough Concentrations at week4</measure>
    <time_frame>week4</time_frame>
    <description>The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1</measure>
    <time_frame>week1</time_frame>
    <description>The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4</measure>
    <time_frame>week4</time_frame>
    <description>The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>0.3% OPA-15406 Ointments</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1% OPA-15406 Ointments</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Ointments</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPA-15406</intervention_name>
    <arm_group_label>0.3% OPA-15406 Ointments</arm_group_label>
    <arm_group_label>1% OPA-15406 Ointments</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <arm_group_label>Placebo Ointments</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of atopic dermatitis based on the criteria of Hanifin and Rajka&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have an atopic dermatitis or contact dermatitis flare-up defined as a&#xD;
             sudden intensification of atopic dermatitis.&#xD;
&#xD;
          -  Subjects who have an active viral skin infection.&#xD;
&#xD;
          -  Subjects with a current or history of malignancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hiroaki Ono, Mr</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Hokkaido Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kanto Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kinki Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyushu Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <results_first_submitted>November 21, 2018</results_first_submitted>
  <results_first_submitted_qc>July 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 23, 2020</results_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</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>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 14, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03018691/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03018691/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>0.3% OPA-15406 Ointments</title>
          <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
        </group>
        <group group_id="P2">
          <title>1% OPA-15406 Ointments</title>
          <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
        </group>
        <group group_id="P3">
          <title>Placebo Ointments</title>
          <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="24"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by parent/guardian</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>0.3% OPA-15406 Ointments</title>
          <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
        </group>
        <group group_id="B2">
          <title>1% OPA-15406 Ointments</title>
          <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
        </group>
        <group group_id="B3">
          <title>Placebo Ointments</title>
          <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</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="24"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="24"/>
            <count group_id="B4" value="73"/>
          </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="24"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.5" spread="3.8"/>
                    <measurement group_id="B2" value="7.9" spread="3.5"/>
                    <measurement group_id="B3" value="8.5" spread="3.1"/>
                    <measurement group_id="B4" value="8.3" spread="3.4"/>
                  </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="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Japanese Subjects</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Number of Subjects Experiencing AEs</title>
        <description>The number of subjects experiencing AEs will be calculated for each treatment group.&#xD;
Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported.</description>
        <time_frame>Week 0-4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Subjects Experiencing AEs</title>
          <description>The number of subjects experiencing AEs will be calculated for each treatment group.&#xD;
Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4</title>
        <description>The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline.</description>
        <time_frame>Baseline and Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4</title>
          <description>The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline.</description>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.50" lower_limit="18.80" upper_limit="59.41"/>
                    <measurement group_id="O2" value="40.00" lower_limit="21.13" upper_limit="61.33"/>
                    <measurement group_id="O3" value="8.33" lower_limit="1.03" upper_limit="27.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Eczema Area and Severity Index (EASI) Score</title>
        <description>The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Eczema Area and Severity Index (EASI) Score</title>
          <description>The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.33" spread="1.28"/>
                    <measurement group_id="O2" value="-5.52" spread="1.26"/>
                    <measurement group_id="O3" value="0.56" spread="1.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score</title>
        <description>The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score</title>
          <description>The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.</description>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.00" spread="7.27"/>
                    <measurement group_id="O2" value="-17.21" spread="7.29"/>
                    <measurement group_id="O3" value="8.19" spread="7.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score</title>
        <description>The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary.&#xD;
0 : None&#xD;
: Mild&#xD;
: Moderate&#xD;
: Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.</description>
        <time_frame>Baseline, Hour 156</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score</title>
          <description>The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary.&#xD;
0 : None&#xD;
: Mild&#xD;
: Moderate&#xD;
: Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.83" spread="0.18"/>
                    <measurement group_id="O2" value="-0.73" spread="0.19"/>
                    <measurement group_id="O3" value="0.30" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score</title>
        <description>The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score</title>
          <description>The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.33" spread="1.16"/>
                    <measurement group_id="O2" value="-4.37" spread="1.14"/>
                    <measurement group_id="O3" value="2.26" spread="1.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Percentage Affected Body Surface Area</title>
        <description>The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA. The negative value showed the degree of improvement.</description>
        <time_frame>Baseline, Week 8, 16, 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406 Ointments</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
          </group>
          <group group_id="O3">
            <title>Placebo Ointments</title>
            <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Percentage Affected Body Surface Area</title>
          <description>The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA. The negative value showed the degree of improvement.</description>
          <units>percentage of Affected Body Surface Area</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.06" spread="2.36"/>
                    <measurement group_id="O2" value="-8.21" spread="2.32"/>
                    <measurement group_id="O3" value="1.78" spread="2.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean (SD) OPA-15406 Plasma Trough Concentrations at week1</title>
        <description>The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.</description>
        <time_frame>Week 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean (SD) OPA-15406 Plasma Trough Concentrations at week1</title>
          <description>The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.842" spread="0.577"/>
                    <measurement group_id="O2" value="2.90" spread="2.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean (SD) OPA-15406 Plasma Trough Concentrations at week4</title>
        <description>The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.</description>
        <time_frame>week4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean (SD) OPA-15406 Plasma Trough Concentrations at week4</title>
          <description>The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.946" spread="1.16"/>
                    <measurement group_id="O2" value="2.21" spread="1.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1</title>
        <description>The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.</description>
        <time_frame>week1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1</title>
          <description>The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.</description>
          <units>ng/mL/mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.196" spread="0.201"/>
                    <measurement group_id="O2" value="0.210" spread="0.174"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4</title>
        <description>The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.</description>
        <time_frame>week4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.3% OPA-15406</title>
            <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.</description>
          </group>
          <group group_id="O2">
            <title>1% OPA-15406</title>
            <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4</title>
          <description>The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.</description>
          <units>ng/mL/mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.150" spread="0.111"/>
                    <measurement group_id="O2" value="0.166" spread="0.148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment period</time_frame>
      <group_list>
        <group group_id="E1">
          <title>0.3% OPA-15406 Ointments</title>
          <description>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
        </group>
        <group group_id="E2">
          <title>1% OPA-15406 Ointments</title>
          <description>Subjects were treated with assigned 1% OPA-15406 ointment twice daily.&#xD;
OPA-15406</description>
        </group>
        <group group_id="E3">
          <title>Placebo Ointments</title>
          <description>Subjects were treated with assigned 0% OPA-15406 ointment twice daily.&#xD;
Placebos</description>
        </group>
      </group_list>
      <serious_events>
        <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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="6" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Otsuka Pharmaceutical Co., LTD.</organization>
      <phone>+81-3-6361-7366</phone>
      <email>CL_OPCJ_RDA_Team@otsuka.jp</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/NCT03018691
org study id: 271-102-00002
secondary id: JapicCTI-173484
nct id: NCT03018691
lead sponsor: 
has dmc: No
To evaluate the safety, efficacy (dose response) and pharmacokinetics of 0.3% and 1%
      OPA-15406 when applied twice daily for 4 weeks in pediatric patients with atopic dermatitis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The Number of Subjects Experiencing AEs
time frame: Week 0-4
description: The number of subjects experiencing AEs will be calculated for each treatment group.
Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported.
measure: Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4
time frame: Baseline and Week 4
description: The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline.
measure: Change From Baseline in Eczema Area and Severity Index (EASI) Score
time frame: Baseline, Week 4
description: The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.
measure: Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score
time frame: Baseline, Week 4
description: The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.
measure: Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score
time frame: Baseline, Hour 156
description: The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary.
0 : None
: Mild
: Moderate
: Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.
measure: Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score
time frame: Baseline, Week 4
description: The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.
measure: Change From Baseline in Percentage Affected Body Surface Area
time frame: Baseline, Week 8, 16, 24
description: The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA. The negative value showed the degree of improvement.
measure: Mean (SD) OPA-15406 Plasma Trough Concentrations at week1
time frame: Week 1
description: The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.
measure: Mean (SD) OPA-15406 Plasma Trough Concentrations at week4
time frame: week4
description: The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.
measure: Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1
time frame: week1
description: The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.
measure: Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4
time frame: week4
description: The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.
arm group label: 0.3% OPA-15406 Ointments
arm group type: Experimental
description: Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.
arm group label: 1% OPA-15406 Ointments
arm group type: Experimental
description: Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
arm group label: Placebo Ointments
arm group type: Placebo Comparator
description: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
intervention type: Drug
intervention name: OPA-15406
arm group label: 0.3% OPA-15406 Ointments
arm group label: 1% OPA-15406 Ointments
intervention type: Drug
intervention name: Placebos
arm group label: Placebo Ointments
criteria: 
gender: All
minimum age: 2 Years
maximum age: 14 Years
healthy volunteers: No
last name: Hiroaki Ono, Mr
role: Study Director
affiliation: Otsuka Pharmaceutical Co., Ltd.
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 