<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/NCT03233529</url>
  </required_header>
  <id_info>
    <org_study_id>C3291001</org_study_id>
    <nct_id>NCT03233529</nct_id>
  </id_info>
  <brief_title>Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis</brief_title>
  <official_title>A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED STUDY, TO CHARACTERIZE THE MECHANISM OF ACTION OF CRISABOROLE OINTMENT 2%, BY EVALUATION OF EFFICACY AND CHANGES IN SKIN BIOMARKERS, IN ADULT SUBJECTS WITH MILD TO MODERATE ATOPIC DERMATITIS, WITH A 4 WEEK OPEN-LABEL EXTENSION</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being conducted to characterize the mechanism of action of crisaborole ointment&#xD;
      2%, by evaluation of efficacy and changes in key skin biomarkers in atopic dermatitis (AD)&#xD;
      lesions treated with crisaborole ointment 2% over vehicle, in subjects with mild to moderate&#xD;
      AD. Two identified AD skin lesions for each subject will be treated for the first 15 days,&#xD;
      one with crisaborole ointment 2% and one with vehicle, in a blinded manner, and biopsies for&#xD;
      biomarker analysis will be performed on the lesions. Following completion of the blinded&#xD;
      treatment period, subjects will start the 28 day open label period during which all AD&#xD;
      affected skin lesions will be treated with crisaborole ointment 2% twice daily.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2017</start_date>
  <completion_date type="Actual">May 4, 2018</completion_date>
  <primary_completion_date type="Actual">May 4, 2018</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>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</measure>
    <time_frame>Baseline (Day 1), Day 15</time_frame>
    <description>TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Categorical Histological Response at Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Categorical KRT16 Expression at Day 15</measure>
    <time_frame>Day 15</time_frame>
    <description>KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Lesion Severity as Measured by TSS at Day 8</measure>
    <time_frame>Baseline (Day 1), Day 8</time_frame>
    <description>The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15</measure>
    <time_frame>Baseline (Day 1), Days 8 and 15</time_frame>
    <description>The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15</measure>
    <time_frame>Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15</time_frame>
    <description>The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups</measure>
    <time_frame>From first dose of study treatment up to Day 71</time_frame>
    <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome Measure).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period</measure>
    <time_frame>From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection</time_frame>
    <description>An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Dermatitis, Atopic</condition>
  <arm_group>
    <arm_group_label>Crisaborole ointment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo ointment (vehicle)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crisaborole ointment 2% BID</intervention_name>
    <description>Crisaborole ointment 2% BID for 15 days (double blind); additional 28 days (open label)</description>
    <arm_group_label>Crisaborole ointment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo ointment (vehicle)</intervention_name>
    <description>Placebo ointment (vehicle) BID for 15 days (double blind)</description>
    <arm_group_label>Placebo ointment (vehicle)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of active atopic dermatitis (AD) with at least 6 month history&#xD;
             prior to Screening and that has been clinically stable for 1 month.&#xD;
&#xD;
          -  Investigator's Static Global Assessment (ISGA) of 2 (mild) or 3 (moderate) at&#xD;
             Baseline.&#xD;
&#xD;
          -  Body surface area (BSA) covered with AD of at least 0.5% and no more than 10% at&#xD;
             Baseline, calculation excluding face, scalp, axilla, genitals, groin area, palms, back&#xD;
             of the hands, and soles.&#xD;
&#xD;
          -  Two lesions of AD at least 3 cm x 3 cm in size and at least 5 cm apart, with identical&#xD;
             Lesion ISGA score of greater than/equal to 3.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically infected AD or requires high potency topical corticosteroids or systemic&#xD;
             (oral/injectable) corticosteroids to manage AD.&#xD;
&#xD;
          -  History of angioedema or anaphylaxis to topical products or known sensitivity to&#xD;
             components of crisaborole ointment 2%.&#xD;
&#xD;
          -  History of cancer (except squamous or basal cell carcinoma or carcinoma in situ of the&#xD;
             skin).&#xD;
&#xD;
          -  Previous treatment with any topical or systemic PDE4 inhibitor unless stopped for the&#xD;
             reason of lack of efficacy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Innovaderm Research Incorporated</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2K 4L5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291001&amp;StudyName=A+Phase+2%2C+Single-center%2C+Randomized%2C+Double-blind+Study+To+Explore+The+Mechanism+Of+Action+Of+Crisaborole+Topical+Ointment+2%25+In+Patients+With+Atopic+Dermatitis</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291001&amp;StudyName=A+Phase+2a%2C+Randomized%2C+Double-blind%2C+Vehicle-controlled+Study%2C+To+Characterize+The+Mechanism+Of+Action+Of+Crisaborole+Ointment+2%25%2C+By+Evaluation+Of+Efficacy+And+Changes+In+Skin+Biomarkers%2C+In+Adult+Subjects+With+Mild+To+Moderate+Atopic+Dermatitis%2C+With+A+4+Week+Open-label+Extension</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>April 26, 2019</results_first_submitted>
  <results_first_submitted_qc>July 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 13, 2019</results_first_posted>
  <last_update_submitted>July 22, 2019</last_update_submitted>
  <last_update_submitted_qc>July 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>atopic dermatitis</keyword>
  <keyword>atopic eczema</keyword>
  <keyword>eczema</keyword>
  <keyword>topical treatment</keyword>
  <keyword>skin diseases</keyword>
  <keyword>phosphodiesterase-4 inhibitor</keyword>
  <keyword>PDE-4 inhibitor</keyword>
  <keyword>crisaborole</keyword>
  <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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
    <ipd_url>https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests</ipd_url>
  </patient_data>
  <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>May 2, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03233529/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>June 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03233529/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2%</title>
          <description>The study consisted of 2 periods, i.e., a double-blind period from Day 1 to Day 15 skin biopsy collection, and an open-label period from Day 15 skin biopsy collection to the end of study (Day 71). Each participant received double-blind topical administration of crisaborole ointment 2 percent (%) for 1 target lesion and placebo ointment vehicle (referred to as vehicle) for the other target lesion (i.e., each participant was treated with both crisaborole and vehicle), twice daily from Day 1 to Day 14; then received open-label topical administration of crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp) twice daily from Day 15 to Day 42.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-Blind Period (Day 1 to Day 15)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open-Label Period (Day 15 to Day 71)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received at least 1 dose of investigational product.</population>
      <group_list>
        <group group_id="B1">
          <title>Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2%</title>
          <description>The study consisted of 2 periods, i.e., a double-blind period from Day 1 to Day 15 skin biopsy collection, and an open-label period from Day 15 skin biopsy collection to the end of study (Day 71). Each participant received double-blind topical administration of crisaborole ointment 2 percent (%) for 1 target lesion and placebo ointment vehicle (referred to as vehicle) for the other target lesion (i.e., each participant was treated with both crisaborole and vehicle), twice daily from Day 1 to Day 14; then received open-label topical administration of crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp) twice daily from Day 15 to Day 42.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.2" spread="11.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product and had TSS assessment at Day 15.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.</description>
          <population>All randomized participants who received at least 1 dose of investigational product and had TSS assessment at Day 15.</population>
          <units>units 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="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.5" spread="0.31"/>
                    <measurement group_id="O2" value="-2.1" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-2.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.35</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.1</ci_lower_limit>
            <ci_upper_limit>-1.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2787" spread="0.36339"/>
                    <measurement group_id="O2" value="-0.2881" spread="0.34055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0420</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.9906</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.48404</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7295" spread="0.25784"/>
                    <measurement group_id="O2" value="-0.1849" spread="0.25272"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1519</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.5446</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.37855</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3267" spread="0.24359"/>
                    <measurement group_id="O2" value="-0.1994" spread="0.22335"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0007</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.1273</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.32552</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5484" spread="0.25767"/>
                    <measurement group_id="O2" value="0.2128" spread="0.27893"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0871</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.7612</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.44266</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4495" spread="0.30229"/>
                    <measurement group_id="O2" value="-1.0854" spread="0.33131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0055</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.3641</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.48603</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4235" spread="0.33463"/>
                    <measurement group_id="O2" value="-1.2989" spread="0.35218"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0238</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.1246</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.49359</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.2762" spread="0.39686"/>
                    <measurement group_id="O2" value="-1.2849" spread="0.40613"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0042</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.9913</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.68659</dispersion_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2-scale micrometers</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2737" spread="0.10653"/>
                    <measurement group_id="O2" value="-0.1779" spread="0.08229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2-scale cells per square millimeter</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CD11c</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4736" spread="0.18946"/>
                    <measurement group_id="O2" value="-0.1694" spread="0.11081"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CD3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6219" spread="0.15152"/>
                    <measurement group_id="O2" value="-0.2642" spread="0.13959"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FceR1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4226" spread="0.16068"/>
                    <measurement group_id="O2" value="-0.1314" spread="0.16513"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ki67</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0983" spread="0.21512"/>
                    <measurement group_id="O2" value="-0.8971" spread="0.19918"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Langerin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3694" spread="0.27896"/>
                    <measurement group_id="O2" value="0.2779" spread="0.19645"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
        <description>TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
        <time_frame>Baseline (Day 1), Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15</title>
          <description>TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>log2(normalized expression)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CCL13</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3095" spread="0.21520"/>
                    <measurement group_id="O2" value="0.0604" spread="0.20967"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CCL20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2016" spread="0.23629"/>
                    <measurement group_id="O2" value="0.1088" spread="0.23212"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CCL26</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0231" spread="0.18602"/>
                    <measurement group_id="O2" value="0.1195" spread="0.22820"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CRLF2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8058" spread="0.13728"/>
                    <measurement group_id="O2" value="-0.2023" spread="0.14431"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CXCL1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4174" spread="0.23956"/>
                    <measurement group_id="O2" value="0.1924" spread="0.32423"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CXCL10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0779" spread="0.36531"/>
                    <measurement group_id="O2" value="0.6697" spread="0.37822"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CXCL2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5462" spread="0.21129"/>
                    <measurement group_id="O2" value="0.1945" spread="0.20700"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CXCL9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9941" spread="0.33692"/>
                    <measurement group_id="O2" value="0.7562" spread="0.39811"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DEFB4A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.5331" spread="0.42635"/>
                    <measurement group_id="O2" value="-1.3456" spread="0.46988"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FLG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2155" spread="0.18503"/>
                    <measurement group_id="O2" value="-0.3670" spread="0.22285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FOXP3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5115" spread="0.12709"/>
                    <measurement group_id="O2" value="-0.0273" spread="0.16057"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IFNG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5588" spread="0.34472"/>
                    <measurement group_id="O2" value="0.5737" spread="0.31138"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3773" spread="0.19458"/>
                    <measurement group_id="O2" value="0.2950" spread="0.17314"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2307" spread="0.12331"/>
                    <measurement group_id="O2" value="0.2193" spread="0.11761"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-15RA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0780" spread="0.10814"/>
                    <measurement group_id="O2" value="0.2110" spread="0.10624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-17A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1577" spread="0.57223"/>
                    <measurement group_id="O2" value="0.7516" spread="0.59970"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-17F</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9482" spread="0.79294"/>
                    <measurement group_id="O2" value="0.5309" spread="0.88038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-19</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.1946" spread="0.78012"/>
                    <measurement group_id="O2" value="-0.8108" spread="0.75460"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5792" spread="0.21864"/>
                    <measurement group_id="O2" value="0.2808" spread="0.29124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5352" spread="0.26229"/>
                    <measurement group_id="O2" value="0.2769" spread="0.16896"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4970" spread="0.39951"/>
                    <measurement group_id="O2" value="-0.0170" spread="0.35503"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-2RA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8836" spread="0.19462"/>
                    <measurement group_id="O2" value="-0.0824" spread="0.22176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-31</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5885" spread="0.60512"/>
                    <measurement group_id="O2" value="-0.3997" spread="0.65363"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-32</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2992" spread="0.16762"/>
                    <measurement group_id="O2" value="0.1878" spread="0.15632"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3487" spread="0.51329"/>
                    <measurement group_id="O2" value="-0.4148" spread="0.42311"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8814" spread="0.32670"/>
                    <measurement group_id="O2" value="0.1724" spread="0.36369"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9805" spread="0.37922"/>
                    <measurement group_id="O2" value="-0.1698" spread="0.42603"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2803" spread="0.71683"/>
                    <measurement group_id="O2" value="-1.0530" spread="0.68305"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-12A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2787" spread="0.20557"/>
                    <measurement group_id="O2" value="0.5251" spread="0.16751"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-23A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2754" spread="0.26058"/>
                    <measurement group_id="O2" value="-0.1173" spread="0.28133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LOR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3759" spread="0.19707"/>
                    <measurement group_id="O2" value="-0.1041" spread="0.21965"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MMP-12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9588" spread="0.39817"/>
                    <measurement group_id="O2" value="-0.4205" spread="0.34033"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PDE4A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0105" spread="0.12015"/>
                    <measurement group_id="O2" value="0.1359" spread="0.11153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PDE4B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1900" spread="0.12061"/>
                    <measurement group_id="O2" value="0.1923" spread="0.10897"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PDE4D</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3865" spread="0.12920"/>
                    <measurement group_id="O2" value="0.0736" spread="0.12231"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PPL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3000" spread="0.09781"/>
                    <measurement group_id="O2" value="-0.1933" spread="0.12180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RNA18SP5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1121" spread="0.08576"/>
                    <measurement group_id="O2" value="-0.0221" spread="0.06550"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>S100A7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1764" spread="0.30729"/>
                    <measurement group_id="O2" value="-0.8782" spread="0.26498"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>S100A8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4454" spread="0.36057"/>
                    <measurement group_id="O2" value="-1.0669" spread="0.33255"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>S100A9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6155" spread="0.35209"/>
                    <measurement group_id="O2" value="-1.2976" spread="0.33324"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15</title>
        <description>FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring.</description>
        <time_frame>Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15</title>
          <description>FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial normalization</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Full normalization</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Worsening</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Categorical Histological Response at Day 15</title>
        <description>Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains.</description>
        <time_frame>Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Categorical Histological Response at Day 15</title>
          <description>Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Non-responder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Responder</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Categorical KRT16 Expression at Day 15</title>
        <description>KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring.</description>
        <time_frame>Day 15</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Categorical KRT16 Expression at Day 15</title>
          <description>KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring.</description>
          <population>All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Slight improvement</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Good improvement</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Excellent improvement</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Worsening</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Lesion Severity as Measured by TSS at Day 8</title>
        <description>The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.</description>
        <time_frame>Baseline (Day 1), Day 8</time_frame>
        <population>All randomized participants who received at least 1 dose of investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lesion Severity as Measured by TSS at Day 8</title>
          <description>The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.</description>
          <population>All randomized participants who received at least 1 dose of investigational product.</population>
          <units>units 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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.3" spread="0.36"/>
                    <measurement group_id="O2" value="-1.2" spread="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-2.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.33</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.7</ci_lower_limit>
            <ci_upper_limit>-1.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15</title>
        <description>The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity.</description>
        <time_frame>Baseline (Day 1), Days 8 and 15</time_frame>
        <population>&quot;Number of Participants Analyzed&quot; signifies the number of participants who received at least 1 dose of investigational product. &quot;Number Analyzed&quot; refers to the number of evaluable participants for specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15</title>
          <description>The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity.</description>
          <population>&quot;Number of Participants Analyzed&quot; signifies the number of participants who received at least 1 dose of investigational product. &quot;Number Analyzed&quot; refers to the number of evaluable participants for specified time points.</population>
          <units>units 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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="0.16"/>
                    <measurement group_id="O2" value="-0.4" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="0.15"/>
                    <measurement group_id="O2" value="-0.8" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.17</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.3</ci_lower_limit>
            <ci_upper_limit>-0.6</ci_upper_limit>
            <estimate_desc>Comparison at Day 8</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-1.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.16</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.4</ci_lower_limit>
            <ci_upper_limit>-0.8</ci_upper_limit>
            <estimate_desc>Comparison at Day 15</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15</title>
        <description>The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity.</description>
        <time_frame>Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15</time_frame>
        <population>&quot;Number of Participants Analyzed&quot; signifies the number of participants who received at least 1 dose of investigational product. &quot;Number Analyzed&quot; refers to the number of evaluable participants for specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15</title>
          <description>The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity.</description>
          <population>&quot;Number of Participants Analyzed&quot; signifies the number of participants who received at least 1 dose of investigational product. &quot;Number Analyzed&quot; refers to the number of evaluable participants for specified time points.</population>
          <units>units 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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="0.36"/>
                    <measurement group_id="O2" value="-1.0" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="0.36"/>
                    <measurement group_id="O2" value="-0.9" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="0.33"/>
                    <measurement group_id="O2" value="-1.1" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" spread="0.31"/>
                    <measurement group_id="O2" value="-1.1" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6" spread="0.34"/>
                    <measurement group_id="O2" value="-1.3" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.1" spread="0.36"/>
                    <measurement group_id="O2" value="-1.5" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.4" spread="0.35"/>
                    <measurement group_id="O2" value="-1.5" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.4" spread="0.32"/>
                    <measurement group_id="O2" value="-1.5" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.5" spread="0.34"/>
                    <measurement group_id="O2" value="-1.6" spread="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.5" spread="0.41"/>
                    <measurement group_id="O2" value="-2.0" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.7" spread="0.40"/>
                    <measurement group_id="O2" value="-1.5" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.0" spread="0.38"/>
                    <measurement group_id="O2" value="-2.2" spread="0.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.9" spread="0.36"/>
                    <measurement group_id="O2" value="-2.2" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.9" spread="0.38"/>
                    <measurement group_id="O2" value="-2.0" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0188</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.6</ci_lower_limit>
            <ci_upper_limit>-0.1</ci_upper_limit>
            <estimate_desc>Comparison at Day 2</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0014</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.9</ci_lower_limit>
            <ci_upper_limit>-0.4</ci_upper_limit>
            <estimate_desc>Comparison at Day 3</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>-0.6</ci_upper_limit>
            <estimate_desc>Comparison at Day 4</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.2</ci_lower_limit>
            <ci_upper_limit>-0.8</ci_upper_limit>
            <estimate_desc>Comparison at Day 5</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>-0.6</ci_upper_limit>
            <estimate_desc>Comparison at Day 6</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.3</ci_lower_limit>
            <ci_upper_limit>-0.8</ci_upper_limit>
            <estimate_desc>Comparison at Day 7</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>-1.1</ci_upper_limit>
            <estimate_desc>Comparison at Day 8</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.6</ci_lower_limit>
            <ci_upper_limit>-1.2</ci_upper_limit>
            <estimate_desc>Comparison at Day 9</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-2.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.7</ci_lower_limit>
            <ci_upper_limit>-1.3</ci_upper_limit>
            <estimate_desc>Comparison at Day 10</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.37</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.3</ci_lower_limit>
            <ci_upper_limit>-0.9</ci_upper_limit>
            <estimate_desc>Comparison at Day 11</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-2.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.9</ci_lower_limit>
            <ci_upper_limit>-1.5</ci_upper_limit>
            <estimate_desc>Comparison at Day 12</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.6</ci_lower_limit>
            <ci_upper_limit>-1.2</ci_upper_limit>
            <estimate_desc>Comparison at Day 13</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.4</ci_lower_limit>
            <ci_upper_limit>-1.0</ci_upper_limit>
            <estimate_desc>Comparison at Day 14</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Crisaborole ointment 2% was superior to vehicle if p-value was &lt;0.05.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least-Square Mean of Difference</param_type>
            <param_value>-1.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.7</ci_lower_limit>
            <ci_upper_limit>-1.2</ci_upper_limit>
            <estimate_desc>Comparison at Day 15</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups</title>
        <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome Measure).</description>
        <time_frame>From first dose of study treatment up to Day 71</time_frame>
        <population>All participants in each treatment group who received at least 1 dose of investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% + Vehicle in Double-Blind Period</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the participants who were treated with both crisaborole ointment 2% and vehicle during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Crisaborole Ointment 2% in Open-Label Period</title>
            <description>On Days 15 to 42, each participant received crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups</title>
          <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome Measure).</description>
          <population>All participants in each treatment group who received at least 1 dose of investigational product.</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="40"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treatment-emergent AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-emergent SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period</title>
        <description>An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used.</description>
        <time_frame>From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection</time_frame>
        <population>This outcome measure was summarized by the treatment areas during the double-blind period; therefore, the analysis population here represents the participants who received at least 1 dose of investigational product for each treatment area in double-blind period.</population>
        <group_list>
          <group group_id="O1">
            <title>Crisaborole Ointment 2% Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Treated Lesion</title>
            <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period</title>
          <description>An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used.</description>
          <population>This outcome measure was summarized by the treatment areas during the double-blind period; therefore, the analysis population here represents the participants who received at least 1 dose of investigational product for each treatment area in double-blind period.</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Application site dermatitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Application site erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Application site pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Application site pruritus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Application site folliculitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post procedural haemorrhage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Procedural pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suture related complication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study treatment up to Day 71</time_frame>
      <desc>Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).</desc>
      <group_list>
        <group group_id="E1">
          <title>Crisaborole Ointment 2% + Vehicle in Double-Blind Period</title>
          <description>On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the participants who were treated with both crisaborole ointment 2% and vehicle during Days 1 to 14.</description>
        </group>
        <group group_id="E2">
          <title>Crisaborole Ointment 2% in Open-Label Period</title>
          <description>On Days 15 to 42, each participant received crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp).</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="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA v21.0</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="27" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Noninfective conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application site pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Application site dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Application site erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Application site paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Application site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Application site folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vulvovaginal candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Suture related complication</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Graft complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </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="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Skin plaque</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </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>Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pfizer ClinicalTrials.gov Call Center</name_or_title>
      <organization>Pfizer, Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.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/NCT03233529
org study id: C3291001
nct id: NCT03233529
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study is being conducted to characterize the mechanism of action of crisaborole ointment
      2%, by evaluation of efficacy and changes in key skin biomarkers in atopic dermatitis (AD)
      lesions treated with crisaborole ointment 2% over vehicle, in subjects with mild to moderate
      AD. Two identified AD skin lesions for each subject will be treated for the first 15 days,
      one with crisaborole ointment 2% and one with vehicle, in a blinded manner, and biopsies for
      biomarker analysis will be performed on the lesions. Following completion of the blinded
      treatment period, subjects will start the 28 day open label period during which all AD
      affected skin lesions will be treated with crisaborole ointment 2% twice daily.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.
measure: Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.
measure: Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.
measure: Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed.
measure: Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
time frame: Baseline (Day 1), Day 15
description: TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
measure: Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15
time frame: Day 15
description: FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring.
measure: Number of Participants With Categorical Histological Response at Day 15
time frame: Day 15
description: Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains.
measure: Number of Participants With Categorical KRT16 Expression at Day 15
time frame: Day 15
description: KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring.
measure: Change From Baseline in Lesion Severity as Measured by TSS at Day 8
time frame: Baseline (Day 1), Day 8
description: The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.
measure: Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15
time frame: Baseline (Day 1), Days 8 and 15
description: The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity.
measure: Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15
time frame: Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
description: The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity.
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups
time frame: From first dose of study treatment up to Day 71
description: AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome Measure).
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period
time frame: From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection
description: An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used.
arm group label: Crisaborole ointment
arm group type: Experimental
arm group label: Placebo ointment (vehicle)
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Crisaborole ointment 2% BID
description: Crisaborole ointment 2% BID for 15 days (double blind); additional 28 days (open label)
arm group label: Crisaborole ointment
intervention type: Drug
intervention name: Placebo ointment (vehicle)
description: Placebo ointment (vehicle) BID for 15 days (double blind)
arm group label: Placebo ointment (vehicle)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Canada
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291001&StudyName=A+Phase+2%2C+Single-center%2C+Randomized%2C+Double-blind+Study+To+Explore+The+Mechanism+Of+Action+Of+Crisaborole+Topical+Ointment+2%25+In+Patients+With+Atopic+Dermatitis
description: To obtain contact information for a study center near you, click here.
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291001&StudyName=A+Phase+2a%2C+Randomized%2C+Double-blind%2C+Vehicle-controlled+Study%2C+To+Characterize+The+Mechanism+Of+Action+Of+Crisaborole+Ointment+2%25%2C+By+Evaluation+Of+Efficacy+And+Changes+In+Skin+Biomarkers%2C+In+Adult+Subjects+With+Mild+To+Moderate+Atopic+Dermatitis%2C+With+A+4+Week+Open-label+Extension
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
sharing ipd: Yes
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
ipd url: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 