<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/NCT03285477</url>
  </required_header>
  <id_info>
    <org_study_id>KX01-AK-003</org_study_id>
    <secondary_id>U1111-1191-8233</secondary_id>
    <nct_id>NCT03285477</nct_id>
  </id_info>
  <brief_title>A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp</brief_title>
  <acronym>AK003</acronym>
  <official_title>A Phase 3, Double-Blind, Vehicle-Controlled, Randomized, Parallel Group, Multicenter, Efficacy and Safety Study of KX2-391 Ointment 1% in Adult Subjects With Actinic Keratosis on the Face or Scalp</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Almirall, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Athenex, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Almirall, S.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase III study is designed to evaluate the efficacy and safety of KX2-391 Ointment in&#xD;
      adult participants when applied to an area of skin containing 4-8 stable, clinically typical&#xD;
      Actinic Keratosis (AK) lesions on the face or scalp.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was a double-blinded, multicenter, activity, and safety study of KX2-391 Ointment&#xD;
      administered topically to the face or scalp of participants with actinic keratosis.&#xD;
&#xD;
      The study consists of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods.&#xD;
      Eligible participants received 5 consecutive days of topical treatment, to be applied at the&#xD;
      study site. Activity (lesion counts) and safety evaluations was performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2017</start_date>
  <completion_date type="Actual">April 24, 2019</completion_date>
  <primary_completion_date type="Actual">May 3, 2018</primary_completion_date>
  <phase>Phase 3</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>This study tested KX2-391 Ointment 1% against a placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All Central Vendors and the sponsor were masked. The sponsor was unblind at the end of Day 57.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions</measure>
    <time_frame>Day 57</time_frame>
    <description>Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57</measure>
    <time_frame>Day 57</time_frame>
    <description>Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (&gt;=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57</measure>
    <time_frame>Days 8, 15, 29 and 57</time_frame>
    <description>Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57</measure>
    <time_frame>3, 6, 9 and 12 months post-Day 57</time_frame>
    <description>Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)</measure>
    <time_frame>Day 57</time_frame>
    <description>Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Pigmentation and Scarring in the Treatment Area</measure>
    <time_frame>Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57</time_frame>
    <description>Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests</measure>
    <time_frame>Baseline (Day 1 predose) up to Day 57</time_frame>
    <description>An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57</measure>
    <time_frame>From Day 57 up to 12-months post-Day 57</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis</measure>
    <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
    <description>Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Safety Observations- Vital Signs</measure>
    <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
    <description>Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Safety Observations- Physical Examination</measure>
    <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
    <description>A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)</measure>
    <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
    <description>ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">351</enrollment>
  <condition>Actinic Keratoses</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
  </arm_group>
  <arm_group>
    <arm_group_label>KX2-391 Ointment 1%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Vehicle Ointment was used in participants with Clinically typical AK on the face or scalp.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KX2-391 Ointment 1%</intervention_name>
    <description>The experimental drug, KX2-391 Ointment 1% was used in participants with Clinically typical AK on the face or scalp.</description>
    <arm_group_label>KX2-391 Ointment 1%</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Males and females greater than or equal to (≥) 18 years old&#xD;
&#xD;
          2. A defined area on the face or scalp contains 4 to 8 clinically typical, visible, and&#xD;
             discrete AK lesions&#xD;
&#xD;
          3. Participants who in the judgment of the Investigator, are in good general health&#xD;
&#xD;
          4. Females must be postmenopausal [greater than (&gt;) 45 years of age with at least 12&#xD;
             months of amenorrhea], surgically sterile (by hysterectomy, bilateral oophorectomy, or&#xD;
             tubal ligation); or, if of childbearing potential, must be using highly effective&#xD;
             contraception for at least 30 days or 1 menstrual cycle, whichever is longer, prior to&#xD;
             study treatment and must agree to continue to use highly effective contraception for&#xD;
             at least 30 days following their last dose of study treatment. Highly effective&#xD;
             contraception includes oral hormonal contraceptives, hormonal contraceptive implant,&#xD;
             injection or patch, intrauterine device or complete abstinence from sexual&#xD;
             intercourse.&#xD;
&#xD;
          5. Sexually active males who have not had a vasectomy, and whose partner is&#xD;
             reproductively capable, must agree to use barrier contraception from Screening through&#xD;
             90 days after their last dose of study treatment.&#xD;
&#xD;
          6. All participants must agree not to donate sperm or eggs or attempt conception from&#xD;
             Screening through 90 days following their last dose of study treatment&#xD;
&#xD;
          7. Willing to avoid excessive sun or UV exposure&#xD;
&#xD;
          8. Able to comprehend and are willing to sign the informed consent form (ICF).&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Clinically atypical and/or rapidly changing AK lesions on the treatment area&#xD;
&#xD;
          2. Location of the selected area is:&#xD;
&#xD;
               -  On any location other than the face or scalp&#xD;
&#xD;
               -  Within 5 cm of an incompletely healed wound&#xD;
&#xD;
               -  Within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma&#xD;
                  (SCC)&#xD;
&#xD;
          3. Been previously treated with KX2-391 Ointment&#xD;
&#xD;
          4. Anticipated need for in-patient hospitalization or in-patient surgery from Day 1 to&#xD;
             Day 57&#xD;
&#xD;
          5. Treatment with 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, diclofenac,&#xD;
             photodynamic therapy, or other treatments for AK within the treatment area or within 2&#xD;
             cm of the treatment area, within 8 weeks prior to the Screening visit&#xD;
&#xD;
          6. Use of the following therapies and/or medications within 2 weeks prior to the&#xD;
             Screening visit:&#xD;
&#xD;
               -  Cosmetic or therapeutic procedures (eg, use of liquid nitrogen, surgical&#xD;
                  excision, curettage, dermabrasion, medium or greater depth chemical peel, laser&#xD;
                  resurfacing) within the treatment area or within 2 cm of the selected treatment&#xD;
                  area&#xD;
&#xD;
               -  Acid-containing therapeutic products (eg, salicylic acid or fruit acids, such as&#xD;
                  alpha- and beta-hydroxyl acids and glycolic acids), topical retinoids, or light&#xD;
                  chemical peels within the treatment area or within 2 cm of the selected treatment&#xD;
                  area&#xD;
&#xD;
               -  Topical salves (non-medicated/non-irritant lotion and cream are acceptable) or&#xD;
                  topical steroids within the treatment area or within 2 cm of the selected&#xD;
                  treatment area; artificial tanners within the treatment area or within 5 cm of&#xD;
                  the selected treatment area&#xD;
&#xD;
          7. Use of the following therapies and/or medications within 4 weeks prior to the&#xD;
             Screening visit:&#xD;
&#xD;
               -  Treatment with immunomodulators (eg, azathioprine), cytotoxic drugs (eg,&#xD;
                  cyclophosphamide, vinblastine, chlorambucil, methotrexate) or&#xD;
                  interferons/interferon inducers&#xD;
&#xD;
               -  Treatment with systemic medications that suppress the immune system (eg,&#xD;
                  cyclosporine, prednisone, methotrexate, alefacept, infliximab)&#xD;
&#xD;
          8. Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months&#xD;
             prior to the Screening visit&#xD;
&#xD;
          9. A history of sensitivity and/or allergy to any of the ingredients in the study&#xD;
             medication&#xD;
&#xD;
         10. A skin disease (eg, atopic dermatitis, psoriasis, eczema) or condition (eg, scarring,&#xD;
             open wounds) that, in the opinion of the Investigator, might interfere with the study&#xD;
             conduct or evaluations, or which exposes the participants to unacceptable risk by&#xD;
             study participation&#xD;
&#xD;
         11. Other significant uncontrolled or unstable medical diseases or conditions that, in the&#xD;
             opinion of the Investigator, would expose the participant to unacceptable risk by&#xD;
             study participation&#xD;
&#xD;
         12. Females who are pregnant or nursing&#xD;
&#xD;
         13. Participated in an investigational drug trial during which an investigational study&#xD;
             medication was administered within 30 days or 5 half-lives of the investigational&#xD;
             product, whichever is longer, before dosing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jane Fang, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Athenex, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Coastal Clinical Research, Inc.</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Research Associates</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center For Dermatology Clinical Research</name>
      <address>
        <city>Fremont</city>
        <state>California</state>
        <zip>94538</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Contour Dermatology</name>
      <address>
        <city>Rancho Mirage</city>
        <state>California</state>
        <zip>92270</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western States Clincial Research, Inc.</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skin care Research, Inc</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Olympian Clinical Research</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of South Florida</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leavitt Medical Associates of Florida d/b/a Ameriderm Research</name>
      <address>
        <city>Ormond Beach</city>
        <state>Florida</state>
        <zip>32174</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arlington Dermatology</name>
      <address>
        <city>Arlington Heights</city>
        <state>Illinois</state>
        <zip>60005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deaconess Clinic Downtown</name>
      <address>
        <city>Evansville</city>
        <state>Indiana</state>
        <zip>47713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Indiana Clinical Trials Center</name>
      <address>
        <city>Plainfield</city>
        <state>Indiana</state>
        <zip>46168</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DelRicht Research</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ActivMed Practices &amp; Research, Inc.</name>
      <address>
        <city>Beverly</city>
        <state>Massachusetts</state>
        <zip>01915</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Clinical Study Center</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skin Specialists PC</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JDR Dermatology Research</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psoriasis Treatment Center of Central New Jersey</name>
      <address>
        <city>East Windsor</city>
        <state>New Jersey</state>
        <zip>08520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Dermatology Associates</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Beth Israel</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skin Search of Rochester, Inc.</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PMG Research of Cary</name>
      <address>
        <city>Cary</city>
        <state>North Carolina</state>
        <zip>27511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OnSite Clinical Solutions, LLC</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28277</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PMG Research of Winston-Salem,LLC</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CTI Clinical Research Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus US</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>J&amp;S Studies, Inc.</name>
      <address>
        <city>College Station</city>
        <state>Texas</state>
        <zip>77845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Institute for Clinical Research, Inc.</name>
      <address>
        <city>Pflugerville</city>
        <state>Texas</state>
        <zip>78660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Clinical Studies</name>
      <address>
        <city>Webster</city>
        <state>Texas</state>
        <zip>77598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatology Research Center, Inc.</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <results_first_submitted>February 16, 2021</results_first_submitted>
  <results_first_submitted_qc>February 16, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2021</results_first_posted>
  <disposition_first_submitted>May 8, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>May 8, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 13, 2020</disposition_first_posted>
  <last_update_submitted>March 19, 2021</last_update_submitted>
  <last_update_submitted_qc>March 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Actinic Keratosis</keyword>
  <keyword>Keratosis</keyword>
  <keyword>Keratosis, Actinic</keyword>
  <keyword>Skin Diseases</keyword>
  <keyword>Actinic Keratoses</keyword>
  <keyword>Precancerous Conditions</keyword>
  <keyword>Neoplasms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratosis, Actinic</mesh_term>
    <mesh_term>Keratosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tirbanibulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>February 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03285477/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03285477/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 31 sites in United States from 18 September 2017 to 24 April 2019.</recruitment_details>
      <pre_assignment_details>A total of 351 participants were enrolled in the study, 176 participants were randomized to the Vehicle control (121 face, 55 scalp treatment) and 175 participants were randomized to KX2-391 Ointment 1 percent (%) (119 face, 56 scalp treatment).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
        </group>
        <group group_id="P2">
          <title>KX2-391 Ointment 1%</title>
          <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment and Response Assessment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="176"/>
                <participants group_id="P2" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="174"/>
                <participants group_id="P2" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawn of Consent</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Recurrence Follow-up Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="55"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal of consent</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>AK recurrence during the Recurrence Follow-Up Period</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="51"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent to treat (ITT) population included all participants randomized in the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
        </group>
        <group group_id="B2">
          <title>KX2-391 Ointment 1%</title>
          <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
        </group>
        <group group_id="B3">
          <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="176"/>
            <count group_id="B2" value="175"/>
            <count group_id="B3" value="351"/>
          </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="70.2" spread="9.41"/>
                    <measurement group_id="B2" value="69.5" spread="8.55"/>
                    <measurement group_id="B3" value="69.9" spread="8.99"/>
                  </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="22"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="154"/>
                    <measurement group_id="B2" value="147"/>
                    <measurement group_id="B3" value="301"/>
                  </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="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="171"/>
                    <measurement group_id="B2" value="173"/>
                    <measurement group_id="B3" value="344"/>
                  </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_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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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_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_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="175"/>
                    <measurement group_id="B2" value="175"/>
                    <measurement group_id="B3" value="350"/>
                  </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_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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of AK Lesions</title>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.9" spread="1.35"/>
                    <measurement group_id="B2" value="5.8" spread="1.28"/>
                    <measurement group_id="B3" value="5.8" spread="1.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions</title>
        <description>Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.</description>
        <time_frame>Day 57</time_frame>
        <population>ITT population included all participants randomized in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions</title>
          <description>Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.</description>
          <population>ITT population included all participants randomized in the study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical significance in the study for Day 57 complete clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>P-value threshold for statistical significance was 0.5%</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57</title>
        <description>Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (&gt;=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.</description>
        <time_frame>Day 57</time_frame>
        <population>ITT population included all participants randomized in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57</title>
          <description>Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (&gt;=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.</description>
          <population>ITT population included all participants randomized in the study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical significance in the study for Day 57 partial clearance rate was analyzed using a Cochran-Mantel-Haenszel model controlling for treatment location (face or scalp) and treatment group (Placebo versus KX2-391 Ointment 1%).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>P-value threshold for statistical significance was 0.5%</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57</title>
        <description>Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).</description>
        <time_frame>Days 8, 15, 29 and 57</time_frame>
        <population>ITT population included all participants randomized in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57</title>
          <description>Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).</description>
          <population>ITT population included all participants randomized in the study.</population>
          <units>lesion count</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="172"/>
                    <count group_id="O2" value="135"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-7" upper_limit="3"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-8" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="175"/>
                    <count group_id="O2" value="162"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-7" upper_limit="2"/>
                    <measurement group_id="O2" value="-4.0" lower_limit="-8" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="173"/>
                    <count group_id="O2" value="174"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-7" upper_limit="4"/>
                    <measurement group_id="O2" value="-4" lower_limit="-8" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-7" upper_limit="5"/>
                    <measurement group_id="O2" value="-5.0" lower_limit="-8" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57</title>
        <description>Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.</description>
        <time_frame>3, 6, 9 and 12 months post-Day 57</time_frame>
        <population>Recurrence Follow-up Population includes participants achieved complete clearance at the Day 57visit. The recurrence rate was evaluated only for KX2-391 Ointment 1% arm, pre-specified in protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57</title>
          <description>Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.</description>
          <population>Recurrence Follow-up Population includes participants achieved complete clearance at the Day 57visit. The recurrence rate was evaluated only for KX2-391 Ointment 1% arm, pre-specified in protocol.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>3 Months Post-Day 57</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="76"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Months Post-Day 57</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>9 Months Post-Day 57</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months Post-Day 57</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)</title>
        <description>Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).</description>
        <time_frame>Day 57</time_frame>
        <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)</title>
          <description>Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).</description>
          <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</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="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Erythema-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140"/>
                    <measurement group_id="O2" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="163"/>
                    <measurement group_id="O2" value="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vesiculation/Pustulation-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="174"/>
                    <measurement group_id="O2" value="158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vesiculation/Pustulation-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vesiculation/Pustulation-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vesiculation/Pustulation-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erosion/Ulceration-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="168"/>
                    <measurement group_id="O2" value="155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erosion/Ulceration-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erosion/Ulceration-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erosion/Ulceration-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Pigmentation and Scarring in the Treatment Area</title>
        <description>Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.</description>
        <time_frame>Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57</time_frame>
        <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Pigmentation and Scarring in the Treatment Area</title>
          <description>Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.</description>
          <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</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="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hypopigmentation: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests</title>
        <description>An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.</description>
        <time_frame>Baseline (Day 1 predose) up to Day 57</time_frame>
        <population>Safety analysis population included all randomized participants who received at least one dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests</title>
          <description>An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.</description>
          <population>Safety analysis population included all randomized participants who received at least one dose of study treatment</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="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62"/>
                    <measurement group_id="O2" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57"/>
                    <measurement group_id="O2" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with events of special interest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57</title>
        <description>An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.</description>
        <time_frame>From Day 57 up to 12-months post-Day 57</time_frame>
        <population>Recurrence Follow-up Population includes participants achieved complete clearance at the Day 57 visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57</title>
          <description>An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.</description>
          <population>Recurrence Follow-up Population includes participants achieved complete clearance at the Day 57 visit.</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="8"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with any AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with any SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with events of special interest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis</title>
        <description>Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.</description>
        <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
        <population>Safety Population included all randomized participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis</title>
          <description>Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.</description>
          <population>Safety Population included all randomized participants who received at least one dose of study treatment.</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="176"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hematology</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>
              <title>Blood chemistry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinalysis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Safety Observations- Vital Signs</title>
        <description>Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.</description>
        <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
        <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Safety Observations- Vital Signs</title>
          <description>Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.</description>
          <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</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="176"/>
                <count group_id="O2" value="175"/>
              </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>Number of Participants With Clinically Significant Safety Observations- Physical Examination</title>
        <description>A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.</description>
        <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
        <population>Safety analysis population included all randomized participants who received at least one dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Safety Observations- Physical Examination</title>
          <description>A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.</description>
          <population>Safety analysis population included all randomized participants who received at least one dose of study treatment</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="176"/>
                <count group_id="O2" value="175"/>
              </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>Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)</title>
        <description>ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.</description>
        <time_frame>From Baseline (Day 1 predose) up to Day 57</time_frame>
        <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
          <group group_id="O2">
            <title>KX2-391 Ointment 1%</title>
            <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)</title>
          <description>ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.</description>
          <population>Safety analysis population consisted of all participants who received at least 1 dose of study treatment.</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="176"/>
                <count group_id="O2" value="175"/>
              </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_list>

    <reported_events>
      <time_frame>From Baseline (Day 1 predose) up to 15 months (12 months post-Day 57)</time_frame>
      <desc>Safety analysis population included all randomized participants who received at least one dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>The Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp</description>
        </group>
        <group group_id="E2">
          <title>KX2-391 Ointment 1%</title>
          <description>KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic valve stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Hairy cell leukaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="62" subjects_at_risk="176"/>
                <counts group_id="E2" subjects_affected="68" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Nodal rhythm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Benign familial pemphigus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Iritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Faeces discoloured</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Sensitivity of teeth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application site discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Application site dryness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Application site pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="176"/>
                <counts group_id="E2" events="23" subjects_affected="11" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Application site paraesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Application site pruritus</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="176"/>
                <counts group_id="E2" events="14" subjects_affected="13" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Application site warmth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergy to arthropod sting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="176"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Labyrinthitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="176"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="176"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Wound infection staphylococcal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Post procedural complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="176"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Spinal column injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Sunburn</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Cardiac murmur</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Glucose urine present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Heart rate increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Heart rate irregular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Protein urine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Protein urine present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Chest wall mass</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Bowen's disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Malignant melanoma in situ</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Seborrhoeic keratosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of head and neck</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Essential tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Parkinson's disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Pulmonary mass</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Actinic keratosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Papule</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Skin odour abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="176"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="176"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="175"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Global Clinical Development</name_or_title>
      <organization>Almirall S.A.</organization>
      <phone>+34932913000</phone>
      <email>rd@almirall.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/NCT03285477
org study id: KX01-AK-003
secondary id: U1111-1191-8233
nct id: NCT03285477
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This Phase III study is designed to evaluate the efficacy and safety of KX2-391 Ointment in
      adult participants when applied to an area of skin containing 4-8 stable, clinically typical
      Actinic Keratosis (AK) lesions on the face or scalp.
This study was a double-blinded, multicenter, activity, and safety study of KX2-391 Ointment
      administered topically to the face or scalp of participants with actinic keratosis.

      The study consists of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods.
      Eligible participants received 5 consecutive days of topical treatment, to be applied at the
      study site. Activity (lesion counts) and safety evaluations was performed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study tested KX2-391 Ointment 1% against a placebo.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All Central Vendors and the sponsor were masked. The sponsor was unblind at the end of Day 57.
measure: Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions
time frame: Day 57
description: Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.
measure: Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57
time frame: Day 57
description: Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (>=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.
measure: Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57
time frame: Days 8, 15, 29 and 57
description: Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).
measure: Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57
time frame: 3, 6, 9 and 12 months post-Day 57
description: Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.
measure: Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR)
time frame: Day 57
description: Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).
measure: Number of Participants With Pigmentation and Scarring in the Treatment Area
time frame: Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57
description: Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.
measure: Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests
time frame: Baseline (Day 1 predose) up to Day 57
description: An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.
measure: Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57
time frame: From Day 57 up to 12-months post-Day 57
description: An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.
measure: Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis
time frame: From Baseline (Day 1 predose) up to Day 57
description: Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.
measure: Number of Participants With Clinically Significant Safety Observations- Vital Signs
time frame: From Baseline (Day 1 predose) up to Day 57
description: Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
measure: Number of Participants With Clinically Significant Safety Observations- Physical Examination
time frame: From Baseline (Day 1 predose) up to Day 57
description: A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.
measure: Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs)
time frame: From Baseline (Day 1 predose) up to Day 57
description: ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.
arm group label: Placebo
arm group type: Placebo Comparator
description: Vehicle Ointment was applied topically once daily for 5 consecutive days on face or scalp
arm group label: KX2-391 Ointment 1%
arm group type: Experimental
description: KX2-391 Ointment 1% was applied topically once daily for 5 consecutive days on face or scalp
intervention type: Drug
intervention name: Placebo
description: Vehicle Ointment was used in participants with Clinically typical AK on the face or scalp.
arm group label: Placebo
intervention type: Drug
intervention name: KX2-391 Ointment 1%
description: The experimental drug, KX2-391 Ointment 1% was used in participants with Clinically typical AK on the face or scalp.
arm group label: KX2-391 Ointment 1%
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jane Fang, MD
role: Study Chair
affiliation: Athenex, Inc.
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country: United States
responsible party type: Sponsor
mesh term: Keratosis, Actinic
mesh term: Keratosis
mesh term: Tirbanibulin
sharing ipd: No
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