<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/NCT03260595</url>
  </required_header>
  <id_info>
    <org_study_id>C3291029</org_study_id>
    <nct_id>NCT03260595</nct_id>
  </id_info>
  <brief_title>A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis</brief_title>
  <official_title>A Phase 1, Single-center, Randomized, Vehicle-controlled, Parallel-cohort Study Of Crisaborole Ointment 2% To Evaluate The Skin Irritation Potential In Adult Japanese Healthy Subjects, And To Evaluate The Safety, Tolerability And Pharmacokinetics In Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis</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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1 parallel-cohort study of crisaborole ointment 2% to evaluate the skin&#xD;
      irritation potential in adult Japanese healthy subjects in Cohort 1, and to evaluate the&#xD;
      safety, tolerability and PK in adult Japanese subjects with mild to moderate AD in Cohort 2.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">November 27, 2017</completion_date>
  <primary_completion_date type="Actual">November 27, 2017</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cohort 1: Skin Irritation Index</measure>
    <time_frame>Day 3 to 4</time_frame>
    <description>The skin irritation index is a common measure of skin irritation potential (safety criteria) of investigational product and derived using skin irritation scores. Individual skin irritation score ranges from 0-4, where 0 = no reaction, 0.5 = mild erythema, 1 = erythema, 2 = erythema with edema and papula, 3 = erythema with edema, papula and small water blister, 4 = large water blister, higher score indicates more skin irritation. For each investigational product, the skin irritation index was calculated as the sum of the maximum individual skin irritation scores divided by the number of evaluable participants and multiplied by 100, which ranged from 0 to 400; where, lower score indicated less skin irritation and higher score indicated more skin irritation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline up to Day 36</time_frame>
    <description>An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 36) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities</measure>
    <time_frame>Baseline up to end of treatment (Day 8)</time_frame>
    <description>Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: Number of Participants With Laboratory Tests Abnormalities</measure>
    <time_frame>Baseline up to end of treatment (Day 8)</time_frame>
    <description>Laboratory tests abnormalities included: hematology (haemoglobin[Hb], haematocrit and erythrocytes&lt;0.8*lower limit of normal[LLN]; erythrocyte mean corpuscular volume, erythrocyte mean corpuscular Hb and erythrocyte mean corpuscular Hb concentration &lt;0.9*LLN and &gt;1.1*upper limit of normal[ULN]; platelets &lt;0.5*LLN and &gt;1.75*ULN; leukocytes &lt;0.6*LLN and &gt;1.5*ULN; lymphocytes/leukocytes[%], neutrophils/leukocytes[%] &lt;0.8*LLN and &gt;1.2*ULN; basophils/leukocytes[%], eosinophils/leukocytes[%], monocytes/leukocytes[% ]&gt;1.2*ULN); clinical chemistry(bilirubin&gt;1.5*ULN; aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase&gt;3.0*ULN; protein and albumin&lt;0.8*LLN and &gt;1.2*ULN; urea nitrogen and creatinine &gt;1.3*ULN; urate&gt;1.2*ULN; sodium &lt;0.95*LLN and &gt;1.05*ULN; potassium, chloride and calcium &lt;0.9*LLN and &gt;1.1*ULN; fasting glucose &lt;0.6*LLN and &gt;1.5*ULN); and urinalysis (pH &lt;4.5 and &gt;8; glucose, ketones, protein, Hb, urobilinogen, bilirubin, nitrite and leukocyte esterase &gt;=1).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities</measure>
    <time_frame>Baseline up to end of treatment (Day 8)</time_frame>
    <description>Criteria for clinically significant ECG abnormalities included: QT interval &gt;=500 milliseconds (msec); QT interval corrected using the Fridericia's formula (QTcF) &gt;=450 msec to &lt;480 msec, &gt;=480 msec and &gt;=500 msec; increase from baseline in QTcF interval &gt;=30 msec to &lt;60 msec and &gt;=60 msec.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline up to Day 29</time_frame>
    <description>An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 29) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Measurable Concentration (AUClast) of Crisaborole and Its Identified Main Oxidative Metabolites</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hours Post-Dose (AUC24) of Crisaborole and Its Identified Main Oxidative Metabolites (AN7602 and AN8323)</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Tau (12 Hours Dosing Interval) (AUCtau) of Crisaborole and Its Identified Main Oxidative Metabolites</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. AUC tau was defined as area under the plasma concentration-time curve from time 0 to time tau, the dosing interval, where tau =12 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for Cmax (Rac, Cmax) was calculated as Cmax on Day 8 divided by Cmax on Day 1. Cmax was the maximum plasma concentration of Crisaborole and its identified main oxidative metabolites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites</measure>
    <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8</time_frame>
    <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 8 divided by AUCtau on Day 1. Dosing interval = 12 hours.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <condition>Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>Crisaborole ointment 2%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>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%</intervention_name>
    <description>Crisaborole ointment 2%</description>
    <arm_group_label>Crisaborole ointment 2%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>Vehicle</description>
    <arm_group_label>Vehicle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Cohort 1&#xD;
&#xD;
          1. Healthy male Japanese subjects who, at the time of screening, are between the ages of&#xD;
             20 and 55 years, inclusive.&#xD;
&#xD;
          2. Healthy skin on which reddening can be easily recognized in the area of the test&#xD;
             fields.&#xD;
&#xD;
        Cohort 2&#xD;
&#xD;
          1. Male or female Japanese subjects aged 20 years to 55 years (inclusive) at the time of&#xD;
             screening, and in generally good health except for AD.&#xD;
&#xD;
          2. Diagnosis of AD based on the criteria of Hanifin and Rajka (1980).&#xD;
&#xD;
          3. Has at least 25% Treatable %BSA on Day 1 (excluding the scalp and designated venous&#xD;
             access areas).&#xD;
&#xD;
          4. Has an Investigator's static global assessment (ISGA) score of Mild (2) or Moderate&#xD;
             (3) on Day 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Cohort 1&#xD;
&#xD;
          1. Subjects who have any visible skin disease at the application site which, in the&#xD;
             opinion of the investigative personnel, will interfere with the evaluation of the test&#xD;
             site reaction.&#xD;
&#xD;
          2. Subjects who have psoriasis and/or active AD/eczema.&#xD;
&#xD;
          3. Subjects who have a history of AD.&#xD;
&#xD;
          4. Subjects who have damaged skin in or around the test sites, including sunburn,&#xD;
             excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous&#xD;
             freckles, or other disfigurations of the test site.&#xD;
&#xD;
          5. Known sensitivity to any of the components of the investigational products.&#xD;
&#xD;
          6. History of the rash to the adhesive plaster, contact dermatitis to metal, or cosmetic&#xD;
             and household articles.&#xD;
&#xD;
        Cohort 2&#xD;
&#xD;
          1. Has any clinically significant medical disorder, condition, disease (including active&#xD;
             or potentially recurrent dermatological conditions other than AD), significant&#xD;
             physical examination or laboratory findings that may interfere with study objectives,&#xD;
             in the Investigator's opinion.&#xD;
&#xD;
          2. Has unstable AD or a consistent requirement for strong to strongest potency topical&#xD;
             corticosteroids to manage AD signs and symptoms.&#xD;
&#xD;
          3. Has a significant active systemic or localized infection, including known actively&#xD;
             infected AD.&#xD;
&#xD;
          4. Has a history or evidence of clinically significant or severe allergies (eg, seasonal,&#xD;
             pet dander, environmental, food) requiring acute or chronic treatment.&#xD;
&#xD;
          5. Has recent or anticipated concomitant use of topical or systemic therapies that might&#xD;
             alter the course of AD.&#xD;
&#xD;
          6. Has a history of recent (within 4 weeks of Day 1) sunbathing, tanning bed use, or&#xD;
             ultraviolet (UV) light B therapy (UVB) or psoralen plus UVA [PUVA]).&#xD;
&#xD;
          7. Has a known sensitivity to any of the components of crisaborole ointment 2%.&#xD;
&#xD;
          8. Pregnant female subjects; breastfeeding female subjects; female subjects of&#xD;
             childbearing potential who are unwilling or unable to use a highly effective method of&#xD;
             contraception as outlined in this protocol for the duration of the study and for at&#xD;
             least 28 days after the last dose of investigational product.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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>Medical Corporation Heishinkai OPHAC Hospital</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka</state>
        <zip>532-0003</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291029&amp;StudyName=A+Phase+1%2C+Single-center%2C+Randomized%2C+Vehicle-controlled%2C+Parallel-cohort+Study+Of+Crisaborole+Ointment+2%25+To+Evaluate+The+Skin+Irritation+Potential+In+Adult+Japanese+Healthy+Subjects%2C+And+To+Evaluate+The+Safety%2C+Tolerability+And+Pharmacokinetics+In+Adult+Japanese+Subjects+With+Mild+To+Moderate+Atopic+Dermatitis</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <results_first_submitted>October 26, 2018</results_first_submitted>
  <results_first_submitted_qc>October 26, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 1, 2019</results_first_posted>
  <last_update_submitted>October 26, 2018</last_update_submitted>
  <last_update_submitted_qc>October 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests</ipd_description>
  </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>July 14, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03260595/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>November 30, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03260595/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Crisaborole Ointment 2% and Vehicle</title>
          <description>Crisaborole ointment 2 percent (%) and matching vehicle was applied topically to 2 randomly assigned, adjacent sites on the skin area field at infrascapular area of the back respectively within each healthy participant under occlusive patch condition on Day 1. Ointment and vehicle were remained under occlusion for 48 hours. Target sites were identified at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: Crisaborole Ointment 2%</title>
          <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is atopic dermatitis [AD]-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 2: Vehicle</title>
          <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis population included all participants who received at least one dose of study medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Crisaborole Ointment 2% and Vehicle</title>
          <description>Crisaborole ointment 2% and matching vehicle was applied topically to 2 randomly assigned, adjacent sites on the skin area field at infrascapular area of the back respectively within each healthy participant under occlusive patch condition on Day 1. Ointment and vehicle were remained under occlusion for 48 hours. Target sites were identified at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2: Crisaborole Ointment 2%</title>
          <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 2: Vehicle</title>
          <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="2"/>
            <count group_id="B4" value="32"/>
          </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="26.2" spread="5.66"/>
                    <measurement group_id="B2" value="35.0" spread="11.28"/>
                    <measurement group_id="B3" value="23.5" spread="4.95"/>
                    <measurement group_id="B4" value="28.8" spread="8.72"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="32"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cohort 1: Skin Irritation Index</title>
        <description>The skin irritation index is a common measure of skin irritation potential (safety criteria) of investigational product and derived using skin irritation scores. Individual skin irritation score ranges from 0-4, where 0 = no reaction, 0.5 = mild erythema, 1 = erythema, 2 = erythema with edema and papula, 3 = erythema with edema, papula and small water blister, 4 = large water blister, higher score indicates more skin irritation. For each investigational product, the skin irritation index was calculated as the sum of the maximum individual skin irritation scores divided by the number of evaluable participants and multiplied by 100, which ranged from 0 to 400; where, lower score indicated less skin irritation and higher score indicated more skin irritation.</description>
        <time_frame>Day 3 to 4</time_frame>
        <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 2, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Crisaborole Ointment 2% and Vehicle</title>
            <description>Crisaborole ointment 2% and matching vehicle was applied topically to 2 randomly assigned, adjacent sites on the skin area field at infrascapular area of the back respectively within each healthy participant under occlusive patch condition on Day 1. Ointment and vehicle were remained under occlusion for 48 hours. Target sites were identified at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 1: Skin Irritation Index</title>
          <description>The skin irritation index is a common measure of skin irritation potential (safety criteria) of investigational product and derived using skin irritation scores. Individual skin irritation score ranges from 0-4, where 0 = no reaction, 0.5 = mild erythema, 1 = erythema, 2 = erythema with edema and papula, 3 = erythema with edema, papula and small water blister, 4 = large water blister, higher score indicates more skin irritation. For each investigational product, the skin irritation index was calculated as the sum of the maximum individual skin irritation scores divided by the number of evaluable participants and multiplied by 100, which ranged from 0 to 400; where, lower score indicated less skin irritation and higher score indicated more skin irritation.</description>
          <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 2, as pre-specified in protocol.</population>
          <units>scores on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole ointment 2%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vehicle</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)</title>
        <description>An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 36) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.</description>
        <time_frame>Baseline up to Day 36</time_frame>
        <population>Safety analysis population included all participants who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Vehicle</title>
            <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)</title>
          <description>An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 36) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.</description>
          <population>Safety analysis population included all participants who received at least one dose of study medication.</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="10"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>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>Primary</type>
        <title>Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities</title>
        <description>Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.</description>
        <time_frame>Baseline up to end of treatment (Day 8)</time_frame>
        <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Vehicle</title>
            <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities</title>
          <description>Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.</description>
          <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</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="10"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cohort 2: Number of Participants With Laboratory Tests Abnormalities</title>
        <description>Laboratory tests abnormalities included: hematology (haemoglobin[Hb], haematocrit and erythrocytes&lt;0.8*lower limit of normal[LLN]; erythrocyte mean corpuscular volume, erythrocyte mean corpuscular Hb and erythrocyte mean corpuscular Hb concentration &lt;0.9*LLN and &gt;1.1*upper limit of normal[ULN]; platelets &lt;0.5*LLN and &gt;1.75*ULN; leukocytes &lt;0.6*LLN and &gt;1.5*ULN; lymphocytes/leukocytes[%], neutrophils/leukocytes[%] &lt;0.8*LLN and &gt;1.2*ULN; basophils/leukocytes[%], eosinophils/leukocytes[%], monocytes/leukocytes[% ]&gt;1.2*ULN); clinical chemistry(bilirubin&gt;1.5*ULN; aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase&gt;3.0*ULN; protein and albumin&lt;0.8*LLN and &gt;1.2*ULN; urea nitrogen and creatinine &gt;1.3*ULN; urate&gt;1.2*ULN; sodium &lt;0.95*LLN and &gt;1.05*ULN; potassium, chloride and calcium &lt;0.9*LLN and &gt;1.1*ULN; fasting glucose &lt;0.6*LLN and &gt;1.5*ULN); and urinalysis (pH &lt;4.5 and &gt;8; glucose, ketones, protein, Hb, urobilinogen, bilirubin, nitrite and leukocyte esterase &gt;=1).</description>
        <time_frame>Baseline up to end of treatment (Day 8)</time_frame>
        <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Vehicle</title>
            <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Number of Participants With Laboratory Tests Abnormalities</title>
          <description>Laboratory tests abnormalities included: hematology (haemoglobin[Hb], haematocrit and erythrocytes&lt;0.8*lower limit of normal[LLN]; erythrocyte mean corpuscular volume, erythrocyte mean corpuscular Hb and erythrocyte mean corpuscular Hb concentration &lt;0.9*LLN and &gt;1.1*upper limit of normal[ULN]; platelets &lt;0.5*LLN and &gt;1.75*ULN; leukocytes &lt;0.6*LLN and &gt;1.5*ULN; lymphocytes/leukocytes[%], neutrophils/leukocytes[%] &lt;0.8*LLN and &gt;1.2*ULN; basophils/leukocytes[%], eosinophils/leukocytes[%], monocytes/leukocytes[% ]&gt;1.2*ULN); clinical chemistry(bilirubin&gt;1.5*ULN; aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase&gt;3.0*ULN; protein and albumin&lt;0.8*LLN and &gt;1.2*ULN; urea nitrogen and creatinine &gt;1.3*ULN; urate&gt;1.2*ULN; sodium &lt;0.95*LLN and &gt;1.05*ULN; potassium, chloride and calcium &lt;0.9*LLN and &gt;1.1*ULN; fasting glucose &lt;0.6*LLN and &gt;1.5*ULN); and urinalysis (pH &lt;4.5 and &gt;8; glucose, ketones, protein, Hb, urobilinogen, bilirubin, nitrite and leukocyte esterase &gt;=1).</description>
          <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</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="10"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities</title>
        <description>Criteria for clinically significant ECG abnormalities included: QT interval &gt;=500 milliseconds (msec); QT interval corrected using the Fridericia's formula (QTcF) &gt;=450 msec to &lt;480 msec, &gt;=480 msec and &gt;=500 msec; increase from baseline in QTcF interval &gt;=30 msec to &lt;60 msec and &gt;=60 msec.</description>
        <time_frame>Baseline up to end of treatment (Day 8)</time_frame>
        <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Vehicle</title>
            <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities</title>
          <description>Criteria for clinically significant ECG abnormalities included: QT interval &gt;=500 milliseconds (msec); QT interval corrected using the Fridericia's formula (QTcF) &gt;=450 msec to &lt;480 msec, &gt;=480 msec and &gt;=500 msec; increase from baseline in QTcF interval &gt;=30 msec to &lt;60 msec and &gt;=60 msec.</description>
          <population>Safety analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</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="10"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)</title>
        <description>An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 29) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.</description>
        <time_frame>Baseline up to Day 29</time_frame>
        <population>Safety analysis population included all participants who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Crisaborole Ointment 2% and Vehicle</title>
            <description>Crisaborole ointment 2% and matching vehicle was applied topically to 2 randomly assigned, adjacent sites on the skin area field at infrascapular area of the back respectively within each healthy participant under occlusive patch condition on Day 1. Ointment and vehicle were remained under occlusion for 48 hours. Target sites were identified at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)</title>
          <description>An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 29) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.</description>
          <population>Safety analysis population included all participants who received at least one dose of study medication.</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="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>nanograms per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="163.7" spread="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crisaborole: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="164.9" spread="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.97" spread="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.83" spread="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3064" spread="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8080" spread="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="3.00" upper_limit="3.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crisaborole: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="3.00" upper_limit="3.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="3.00" upper_limit="3.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="3.00" upper_limit="3.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="3.00" upper_limit="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.000" lower_limit="3.00" upper_limit="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Measurable Concentration (AUClast) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Measurable Concentration (AUClast) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>hours*nanograms per milliliter(hr*ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1171" spread="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crisaborole: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1527" spread="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="601.9" spread="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="565.5" spread="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57560" spread="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="169100" spread="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hours Post-Dose (AUC24) of Crisaborole and Its Identified Main Oxidative Metabolites (AN7602 and AN8323)</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hours Post-Dose (AUC24) of Crisaborole and Its Identified Main Oxidative Metabolites (AN7602 and AN8323)</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>hr*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1171" spread="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crisaborole: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1527" spread="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="601.9" spread="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="565.5" spread="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57560" spread="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="169100" spread="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Tau (12 Hours Dosing Interval) (AUCtau) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. AUC tau was defined as area under the plasma concentration-time curve from time 0 to time tau, the dosing interval, where tau =12 hours.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Tau (12 Hours Dosing Interval) (AUCtau) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. AUC tau was defined as area under the plasma concentration-time curve from time 0 to time tau, the dosing interval, where tau =12 hours.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>hr*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="928.9" spread="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crisaborole: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1123" spread="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="500.4" spread="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="434.9" spread="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29360" spread="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90360" spread="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for Cmax (Rac, Cmax) was calculated as Cmax on Day 8 divided by Cmax on Day 1. Cmax was the maximum plasma concentration of Crisaborole and its identified main oxidative metabolites.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for Cmax (Rac, Cmax) was calculated as Cmax on Day 8 divided by Cmax on Day 1. Cmax was the maximum plasma concentration of Crisaborole and its identified main oxidative metabolites.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.007" spread="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7247" spread="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.638" spread="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
        <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 8 divided by AUCtau on Day 1. Dosing interval = 12 hours.</description>
        <time_frame>Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8</time_frame>
        <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 2: Crisaborole Ointment 2%</title>
            <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
          </group>
        </group_list>
        <measure>
          <title>Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites</title>
          <description>AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 8 divided by AUCtau on Day 1. Dosing interval = 12 hours.</description>
          <population>PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1, as pre-specified in protocol.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Crisaborole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.209" spread="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN7602</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8688" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AN8323</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.080" spread="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Day 29 for Cohort 1 and Day 36 for Cohort 2</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: Crisaborole Ointment 2% and Vehicle</title>
          <description>Crisaborole ointment 2% and matching vehicle was applied topically to 2 randomly assigned, adjacent sites on the skin area field at infrascapular area of the back respectively within each healthy participant under occlusive patch condition on Day 1. Ointment and vehicle were remained under occlusion for 48 hours. Target sites were identified at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2: Crisaborole Ointment 2%</title>
          <description>Crisaborole ointment 2% was applied topically to the treatable percent body surface area (%BSA: defined as percent of a participant's total BSA that is AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 2: Vehicle</title>
          <description>Vehicle matched to Crisaborole ointment 2% was applied topically to the treatable %BSA (defined as percent of a participant's total BSA that AD-involved and is not on the scalp or in designated venous access areas) of participants with AD twice daily from Days 2 to 7 and once only on Days 1 and 8. Treatable %BSA was calculated at Baseline (Day 1) by investigator.</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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA v20.1</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="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eyelid oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application site coldness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Application site irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Application site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Application site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </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="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </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/NCT03260595
org study id: C3291029
nct id: NCT03260595
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a Phase 1 parallel-cohort study of crisaborole ointment 2% to evaluate the skin
      irritation potential in adult Japanese healthy subjects in Cohort 1, and to evaluate the
      safety, tolerability and PK in adult Japanese subjects with mild to moderate AD in Cohort 2.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Cohort 1: Skin Irritation Index
time frame: Day 3 to 4
description: The skin irritation index is a common measure of skin irritation potential (safety criteria) of investigational product and derived using skin irritation scores. Individual skin irritation score ranges from 0-4, where 0 = no reaction, 0.5 = mild erythema, 1 = erythema, 2 = erythema with edema and papula, 3 = erythema with edema, papula and small water blister, 4 = large water blister, higher score indicates more skin irritation. For each investigational product, the skin irritation index was calculated as the sum of the maximum individual skin irritation scores divided by the number of evaluable participants and multiplied by 100, which ranged from 0 to 400; where, lower score indicated less skin irritation and higher score indicated more skin irritation.
measure: Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
time frame: Baseline up to Day 36
description: An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 36) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.
measure: Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities
time frame: Baseline up to end of treatment (Day 8)
description: Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.
measure: Cohort 2: Number of Participants With Laboratory Tests Abnormalities
time frame: Baseline up to end of treatment (Day 8)
description: Laboratory tests abnormalities included: hematology (haemoglobin[Hb], haematocrit and erythrocytes<0.8*lower limit of normal[LLN]; erythrocyte mean corpuscular volume, erythrocyte mean corpuscular Hb and erythrocyte mean corpuscular Hb concentration <0.9*LLN and >1.1*upper limit of normal[ULN]; platelets <0.5*LLN and >1.75*ULN; leukocytes <0.6*LLN and >1.5*ULN; lymphocytes/leukocytes[%], neutrophils/leukocytes[%] <0.8*LLN and >1.2*ULN; basophils/leukocytes[%], eosinophils/leukocytes[%], monocytes/leukocytes[% ]>1.2*ULN); clinical chemistry(bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase>3.0*ULN; protein and albumin<0.8*LLN and >1.2*ULN; urea nitrogen and creatinine >1.3*ULN; urate>1.2*ULN; sodium <0.95*LLN and >1.05*ULN; potassium, chloride and calcium <0.9*LLN and >1.1*ULN; fasting glucose <0.6*LLN and >1.5*ULN); and urinalysis (pH <4.5 and >8; glucose, ketones, protein, Hb, urobilinogen, bilirubin, nitrite and leukocyte esterase >=1).
measure: Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
time frame: Baseline up to end of treatment (Day 8)
description: Criteria for clinically significant ECG abnormalities included: QT interval >=500 milliseconds (msec); QT interval corrected using the Fridericia's formula (QTcF) >=450 msec to <480 msec, >=480 msec and >=500 msec; increase from baseline in QTcF interval >=30 msec to <60 msec and >=60 msec.
measure: Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
time frame: Baseline up to Day 29
description: An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 29) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.
measure: Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
measure: Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
measure: Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Measurable Concentration (AUClast) of Crisaborole and Its Identified Main Oxidative Metabolites
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
measure: Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hours Post-Dose (AUC24) of Crisaborole and Its Identified Main Oxidative Metabolites (AN7602 and AN8323)
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
measure: Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Tau (12 Hours Dosing Interval) (AUCtau) of Crisaborole and Its Identified Main Oxidative Metabolites
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. AUC tau was defined as area under the plasma concentration-time curve from time 0 to time tau, the dosing interval, where tau =12 hours.
measure: Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for Cmax (Rac, Cmax) was calculated as Cmax on Day 8 divided by Cmax on Day 1. Cmax was the maximum plasma concentration of Crisaborole and its identified main oxidative metabolites.
measure: Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites
time frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8
description: AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 8 divided by AUCtau on Day 1. Dosing interval = 12 hours.
arm group label: Crisaborole ointment 2%
arm group type: Experimental
arm group label: Vehicle
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Crisaborole ointment 2%
description: Crisaborole ointment 2%
arm group label: Crisaborole ointment 2%
intervention type: Drug
intervention name: Vehicle
description: Vehicle
arm group label: Vehicle
criteria: 
gender: All
minimum age: 20 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Japan
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291029&StudyName=A+Phase+1%2C+Single-center%2C+Randomized%2C+Vehicle-controlled%2C+Parallel-cohort+Study+Of+Crisaborole+Ointment+2%25+To+Evaluate+The+Skin+Irritation+Potential+In+Adult+Japanese+Healthy+Subjects%2C+And+To+Evaluate+The+Safety%2C+Tolerability+And+Pharmacokinetics+In+Adult+Japanese+Subjects+With+Mild+To+Moderate+Atopic+Dermatitis
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: No
ipd description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 