<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/NCT03760042</url>
  </required_header>
  <id_info>
    <org_study_id>C3291042</org_study_id>
    <nct_id>NCT03760042</nct_id>
  </id_info>
  <brief_title>Study To Assess Local Tolerability of Crisaborole 2% Ointment and Vehicle Ointment In Healthy Participants Using Subject-reported Assessments and Objective Measurements</brief_title>
  <official_title>PHASE 1 RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, INTRA-SUBJECT STUDY TO ASSESS LOCAL TOLERABILITY OF CRISABOROLE 2% OINTMENT AND VEHICLE IN HEALTHY PARTICIPANTS USING SUBJECT-REPORTED ASSESSMENTS AND OBJECTIVE MEASUREMENTS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A double-blind within-subject study to estimate observed application site adverse events&#xD;
      following topical applications of crisaborole and vehicle in healthy participants&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To further understand the potential for crisaborole to evoke skin irritancy, a within-subject&#xD;
      comparison study, C3291042 will assess the local tolerability of crisaborole 5 mg/cm² in&#xD;
      healthy participants, who have had baseline assessments of surrogate markers of skin&#xD;
      sensitivity-i.e. current perception threshold (CPT) measurements and standardized lactic acid&#xD;
      stinging test (LAST) assessments. To further the clinical understanding of application site&#xD;
      pain, responses to crisaborole ointment compared to crisaborole vehicle ointment will be&#xD;
      assessed in comparisons based upon CPT (low versus high; symmetry versus asymmetry) and&#xD;
      response to LAST (&quot;stingers&quot; versus &quot;non-stingers&quot;). This exploration of skin sensitivity&#xD;
      characterizations in healthy participants exposed to crisaborole 5 mg/cm² will assess&#xD;
      application site burning, stinging, and pain as well as other application site&#xD;
      characteristics selected from a MedDRA-based list of terms by the participants. More advanced&#xD;
      understanding of baseline application site sensation in healthy participants prior to higher&#xD;
      local application rate of topical crisaborole may provide strategies for topical dermatologic&#xD;
      product development programs striving to prevent or minimize application site sensory adverse&#xD;
      events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 14, 2018</start_date>
  <completion_date type="Actual">April 15, 2019</completion_date>
  <primary_completion_date type="Actual">April 15, 2019</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>
    <intervention_model_description>Using surrogate markers of skin sensitivity (current perception threshold and lactic acid stinging test responses) to stratify risk for developing application site treatment emergent adverse events (AS-TEAEs), within-subject comparisons will quantify AS-TEAE frequency and severity in healthy participants following double-blind applications of crisaborole ointment and vehicle ointment at 7 sensitive skin anatomic locations.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Crisaborole 2% ointment and matching crisaborole vehicle will be supplied by Pfizer to the CRU as packaged 60 gram tubes and labeled according to local regulatory requirements in an unblinded fashion.&#xD;
Crisaborole and vehicle ointment doses for the 14 pre-specified application sites bilaterally will be prepared by the unblinded PCRU pharmacist and provided to the blinded investigational site staff in individual dose containers. Subjects will be blinded to side of body treated with crisaborole and side of body treated with vehicle.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency and Severity of Application site treatment emergent adverse events (TEAEs) in crisaborole treated versus vehicle-treated prespecified sensitive skin sites</measure>
    <time_frame>3 days</time_frame>
    <description>Comparison of investigator-reported (Application Site Skin Examination [0 to 3 points]) and participant-reported (Local Tolerability Assessment Scale scores [0 to 3 points]) application site TEAEs in crisaborole treated versus vehicle-treated at all 7 prespecified sensitive skin sites.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neurometric Measurement (Current Perception Threshold in mAmps) on Right-side and Left-side of Body (face, upper and lower extremities bilaterally)</measure>
    <time_frame>1 day</time_frame>
    <description>Comparison of Current Perception Threshold (CPT) measurements in participants bilaterally (face, upper extremities, lower extremities) to summarize CPT (absolute value in milliAmperes and right-left differential in milliAmperes) prior to study drug dosing (CPT assessments performed at 5 Hz, 250 Hz, and 2000 Hz) .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantify Participant's response to Lactic Acid Stinging Test (LAST) utilizing the Local Tolerability Assessment Scale (ranging from 0 to 3 points) to categorize as Stinger or Non-stinger</measure>
    <time_frame>1 day</time_frame>
    <description>Lactic Acid Stinging Test assessment showing Local Tolerability Assessment Scale score of 2 or 3 on lactic acid treated side AND a difference of at least 1 between lactic acid treated side and placebo treated side (ie, &quot;stingers&quot;) versus Local Tolerability Assessment Scale score [ranging from 0 to 3 points] of 1 or less on lactic acid treated side (ie, &quot;non-stingers&quot;).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Group A (Crisaborole RIGHT SIDE / Vehicle LEFT SIDE)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Crisaborole ointment 2% applied to sensitive skin locations on right side of body. Crisaborole placebo vehicle ointment applied to sensitive skin locations on left side of body</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B (Crisaborole LEFT SIDE / Vehicle RIGHT SIDE)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Crisaborole placebo vehicle ointment applied to 7 sensitive skin sites on right side of body.&#xD;
Crisaborole ointment 2% applied to 7 sensitive skin locations on left side of body</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Within-Subject Active vs Placebo Topical Applications</intervention_name>
    <description>Crisaborole 2% ointment (right side) and Placebo vehicle ointment (left side)</description>
    <arm_group_label>Group A (Crisaborole RIGHT SIDE / Vehicle LEFT SIDE)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Within-Subject Active vs. Placebo Topical Applications</intervention_name>
    <description>Crisaborole 2% ointment (left side) and Placebo vehicle ointment (right side)</description>
    <arm_group_label>Group B (Crisaborole LEFT SIDE / Vehicle RIGHT SIDE)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female adult participants who are overtly healthy as determined by medical&#xD;
             evaluation including medical history, physical examination, and laboratory tests.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior self-reported history of any chronic relapsing inflammatory skin disease,&#xD;
             including atopic dermatitis.&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or&#xD;
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,&#xD;
             seasonal allergies at the time of dosing). Any clinically significant medical&#xD;
             conditions or history of such conditions that, in the opinion of the Investigator may&#xD;
             place the participant at an unacceptable risk as a participant in this trial.&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C;&#xD;
             positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core&#xD;
             antibody (HBcAb), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.&#xD;
&#xD;
          -  History of serious adverse reactions or hypersensitivity to any topical drug (eg,&#xD;
             crisaborole); or known allergy to any of the test product(s) or any components (eg,&#xD;
             lactic acid) in the test product(s) or history of hypersensitivity; or allergic&#xD;
             reactions to any of the study preparations&#xD;
&#xD;
          -  Abnormal physical findings of clinical significance or dermatological condition (eg&#xD;
             extensive tattooing or excessive scarring at 14 sensitive skin application sites) at&#xD;
             the Screening examination or Baseline which would interfere with the objectives of the&#xD;
             study in the opinion of the Principal Investigator.&#xD;
&#xD;
          -  Daily use of medications that could interfere with the objectives of the study (such&#xD;
             as lidocaine, gabapentin, pregabalin, narcotics, antihistamines, oral or parenteral&#xD;
             corticosteroids, non-narcotic analgesics and anti-inflammatories) within 1 week of&#xD;
             screening and during the study.&#xD;
&#xD;
          -  Not willing to refrain from shaving, the use of depilatories or other hair-removal&#xD;
             activities, antiperspirants, lotions, skin creams, fragrances or perfumes, or body&#xD;
             oils (eg, baby oil; coconut oil), use of hair products, hair gels, and hair oil in the&#xD;
             treatment areas for 48 hours prior to admission to the PCRU and for the duration of&#xD;
             the stay in the PCRU.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 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>New Haven Clinical Research Unit</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291042&amp;StudyName=Phase+1+Randomized%2C+Double-blind%2C+Vehicle-controlled%2C+Intra-subject+Study+To+Assess+Local+Tolerability+Of+Crisaborole+2%25+Ointment+And+Vehicle+In+Healthy+Participants+Using+Subject-reported+Assessments+And+Objective+Measurements</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>June 21, 2019</last_update_submitted>
  <last_update_submitted_qc>June 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03760042
org study id: C3291042
nct id: NCT03760042
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A double-blind within-subject study to estimate observed application site adverse events
      following topical applications of crisaborole and vehicle in healthy participants
To further understand the potential for crisaborole to evoke skin irritancy, a within-subject
      comparison study, C3291042 will assess the local tolerability of crisaborole 5 mg/cm² in
      healthy participants, who have had baseline assessments of surrogate markers of skin
      sensitivity-i.e. current perception threshold (CPT) measurements and standardized lactic acid
      stinging test (LAST) assessments. To further the clinical understanding of application site
      pain, responses to crisaborole ointment compared to crisaborole vehicle ointment will be
      assessed in comparisons based upon CPT (low versus high; symmetry versus asymmetry) and
      response to LAST ("stingers" versus "non-stingers"). This exploration of skin sensitivity
      characterizations in healthy participants exposed to crisaborole 5 mg/cm² will assess
      application site burning, stinging, and pain as well as other application site
      characteristics selected from a MedDRA-based list of terms by the participants. More advanced
      understanding of baseline application site sensation in healthy participants prior to higher
      local application rate of topical crisaborole may provide strategies for topical dermatologic
      product development programs striving to prevent or minimize application site sensory adverse
      events.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Using surrogate markers of skin sensitivity (current perception threshold and lactic acid stinging test responses) to stratify risk for developing application site treatment emergent adverse events (AS-TEAEs), within-subject comparisons will quantify AS-TEAE frequency and severity in healthy participants following double-blind applications of crisaborole ointment and vehicle ointment at 7 sensitive skin anatomic locations.
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
masking description: Crisaborole 2% ointment and matching crisaborole vehicle will be supplied by Pfizer to the CRU as packaged 60 gram tubes and labeled according to local regulatory requirements in an unblinded fashion.
Crisaborole and vehicle ointment doses for the 14 pre-specified application sites bilaterally will be prepared by the unblinded PCRU pharmacist and provided to the blinded investigational site staff in individual dose containers. Subjects will be blinded to side of body treated with crisaborole and side of body treated with vehicle.
measure: Frequency and Severity of Application site treatment emergent adverse events (TEAEs) in crisaborole treated versus vehicle-treated prespecified sensitive skin sites
time frame: 3 days
description: Comparison of investigator-reported (Application Site Skin Examination [0 to 3 points]) and participant-reported (Local Tolerability Assessment Scale scores [0 to 3 points]) application site TEAEs in crisaborole treated versus vehicle-treated at all 7 prespecified sensitive skin sites.
measure: Neurometric Measurement (Current Perception Threshold in mAmps) on Right-side and Left-side of Body (face, upper and lower extremities bilaterally)
time frame: 1 day
description: Comparison of Current Perception Threshold (CPT) measurements in participants bilaterally (face, upper extremities, lower extremities) to summarize CPT (absolute value in milliAmperes and right-left differential in milliAmperes) prior to study drug dosing (CPT assessments performed at 5 Hz, 250 Hz, and 2000 Hz) .
measure: Quantify Participant's response to Lactic Acid Stinging Test (LAST) utilizing the Local Tolerability Assessment Scale (ranging from 0 to 3 points) to categorize as Stinger or Non-stinger
time frame: 1 day
description: Lactic Acid Stinging Test assessment showing Local Tolerability Assessment Scale score of 2 or 3 on lactic acid treated side AND a difference of at least 1 between lactic acid treated side and placebo treated side (ie, "stingers") versus Local Tolerability Assessment Scale score [ranging from 0 to 3 points] of 1 or less on lactic acid treated side (ie, "non-stingers").
arm group label: Group A (Crisaborole RIGHT SIDE / Vehicle LEFT SIDE)
arm group type: Other
description: Crisaborole ointment 2% applied to sensitive skin locations on right side of body. Crisaborole placebo vehicle ointment applied to sensitive skin locations on left side of body
arm group label: Group B (Crisaborole LEFT SIDE / Vehicle RIGHT SIDE)
arm group type: Other
description: Crisaborole placebo vehicle ointment applied to 7 sensitive skin sites on right side of body.
Crisaborole ointment 2% applied to 7 sensitive skin locations on left side of body
intervention type: Drug
intervention name: Within-Subject Active vs Placebo Topical Applications
description: Crisaborole 2% ointment (right side) and Placebo vehicle ointment (left side)
arm group label: Group A (Crisaborole RIGHT SIDE / Vehicle LEFT SIDE)
intervention type: Drug
intervention name: Within-Subject Active vs. Placebo Topical Applications
description: Crisaborole 2% ointment (left side) and Placebo vehicle ointment (right side)
arm group label: Group B (Crisaborole LEFT SIDE / Vehicle RIGHT SIDE)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: United States
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291042&StudyName=Phase+1+Randomized%2C+Double-blind%2C+Vehicle-controlled%2C+Intra-subject+Study+To+Assess+Local+Tolerability+Of+Crisaborole+2%25+Ointment+And+Vehicle+In+Healthy+Participants+Using+Subject-reported+Assessments+And+Objective+Measurements
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
sharing ipd: No
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.