<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/NCT03285490</url>
  </required_header>
  <id_info>
    <org_study_id>KX01-AK-004</org_study_id>
    <secondary_id>U1111-1191-8287</secondary_id>
    <nct_id>NCT03285490</nct_id>
  </id_info>
  <brief_title>A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)</brief_title>
  <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 was designed to evaluate the efficacy and safety of KX2-391 Ointment 1%&#xD;
      in adult participants when applied to an area of skin containing 4-8 stable, clinically&#xD;
      typical actinic keratosis (AK) lesions on the face or scalp.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was a double-blinded, multicenter, efficacy, and safety study of KX2-391 ointment&#xD;
      administered topically to the face or scalp of participants with AK.&#xD;
&#xD;
      The study consisted of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods.&#xD;
      Eligible participants received up to 5 consecutive days of topical treatment. Efficacy&#xD;
      (lesion counts) and safety evaluations were performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">April 24, 2019</completion_date>
  <primary_completion_date type="Actual">May 7, 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 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. 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 Keratosis</condition>
  <arm_group>
    <arm_group_label>KX2-391 Ointment 1%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KX2-391 Ointment was applied once daily for 5 consecutive days on the face or scalp.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The Vehicle Ointment was applied once daily for 5 consecutive days on the face or scalp.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KX2-391 Ointment 1%</intervention_name>
    <description>Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical</description>
    <arm_group_label>KX2-391 Ointment 1%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Dosage form: Ointment; Route of administration: Topical</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Males and females greater than or equal to (&gt;=) 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, were in good general health.&#xD;
&#xD;
          4. Females were postmenopausal (greater than [&gt;] 45 years of age with at least 12 months&#xD;
             of amenorrhea), surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal&#xD;
             ligation); or, if of childbearing potential, were using highly effective contraception&#xD;
             for at least 30 days or 1 menstrual cycle, whichever was longer, prior to study&#xD;
             treatment and agreed to continue to use highly effective contraception for at least 30&#xD;
             days following their last dose of study treatment. Highly effective contraception&#xD;
             includes oral hormonal contraceptives, hormonal contraceptive implant, injection or&#xD;
             patch, intrauterine device or complete abstinence from sexual intercourse.&#xD;
&#xD;
          5. Sexually active males who had not had a vasectomy, and whose partner was&#xD;
             reproductively capable, must had agreed to use barrier contraception from Screening&#xD;
             through 90 days after their last dose of study treatment.&#xD;
&#xD;
          6. All participants must had agreed not to donate sperm or eggs or attempt conception&#xD;
             from Screening through 90 days following their last dose of study treatment.&#xD;
&#xD;
          7. Willing to avoid excessive sun or ultraviolet exposure.&#xD;
&#xD;
          8. Able to comprehend and were 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 centimeters (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 (e.g., 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 were 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 (e.g., atopic dermatitis, psoriasis, eczema) or condition (e.g.,&#xD;
             scarring, open wounds) that, in the opinion of the Investigator, might interfere with&#xD;
             the study conduct or evaluations, or which exposes the participant to unacceptable&#xD;
             risk by 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 were 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 was 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>Alliance Dermatology</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus US</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Burke Pharmaceutical Research</name>
      <address>
        <city>Hot Springs</city>
        <state>Arkansas</state>
        <zip>71913</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatology Specialists, Inc.</name>
      <address>
        <city>Murrieta</city>
        <state>California</state>
        <zip>92562</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatology Specialists, Inc.</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skin Surgery Medical Group, Inc.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AboutSkin Dermatology</name>
      <address>
        <city>Greenwood Village</city>
        <state>Colorado</state>
        <zip>80111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Protocol, Inc</name>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <zip>33437</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sweet Hope Research Specialty, Inc.</name>
      <address>
        <city>Miami Lakes</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Forward Clinical Trials, Inc.</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33624</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laser &amp; Skin Surgery Center of Indiana</name>
      <address>
        <city>Carmel</city>
        <state>Indiana</state>
        <zip>46032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dawes Fretzin Clinical Research Group</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DS Research</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of SWLA, LLC</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamzavi Dermatology</name>
      <address>
        <city>Fort Gratiot</city>
        <state>Michigan</state>
        <zip>48059</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisearch Clinical Trials</name>
      <address>
        <city>Saint Joseph</city>
        <state>Missouri</state>
        <zip>64506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henderson Dermatology Research</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Activmed Practices &amp; Research, Inc</name>
      <address>
        <city>Portsmouth</city>
        <state>New Hampshire</state>
        <zip>03801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Union Square Laser Dermatology</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aventiv Research Inc.</name>
      <address>
        <city>Dublin</city>
        <state>Ohio</state>
        <zip>43016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Medical Research Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97223</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center of the Carolinas</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatology Associates Of Knoxville, PC</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37917</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rivergate Dermatology Clinical Research</name>
      <address>
        <city>Springfield</city>
        <state>Tennessee</state>
        <zip>37072</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DermResearch</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78759</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suzanne Bruce and Associates, P.A., The Center for Skin Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of Texas, Inc.</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Education &amp; Research Foundation, Inc.</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatology Associates of Seattle</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 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>February 16, 2021</last_update_submitted>
  <last_update_submitted_qc>February 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 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>Precancerous Conditions</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>Sun Damaged Skin</keyword>
  <keyword>Actinic Keratoses</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/90/NCT03285490/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/90/NCT03285490/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 31 sites in the United States between 15-September-2017 to 24-April-2019.</recruitment_details>
      <pre_assignment_details>A total of 410 participants were screened, of which 351 participants were enrolled, 173 were randomized to vehicle control (118 face, 55 scalp) and 178 to KX2-391 ointment 1 percent (%) (119 face, 59 scalp). This study consisted of 2 periods i.e., Treatment and response assessment period (Baseline up to Day 57) followed by Recurrence follow-up period (12 months post-Day 57).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 centimeter square (cm^2) 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 in a treatment area of 25 cm^2 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="173"/>
                <participants group_id="P2" count="178"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="173"/>
                <participants group_id="P2" count="178"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Recurrence Follow-up Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="61"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>AK recurrence during Recurrence Follow-Up Period</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="60"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat (ITT) population included all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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="173"/>
            <count group_id="B2" value="178"/>
            <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="8.86"/>
                    <measurement group_id="B2" value="69.1" spread="8.69"/>
                    <measurement group_id="B3" value="69.7" spread="8.78"/>
                  </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="23"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="150"/>
                    <measurement group_id="B2" value="158"/>
                    <measurement group_id="B3" value="308"/>
                  </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="8"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="165"/>
                    <measurement group_id="B2" value="167"/>
                    <measurement group_id="B3" value="332"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <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="173"/>
                    <measurement group_id="B2" value="177"/>
                    <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 at baseline</title>
          <units>lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.8" spread="1.20"/>
                    <measurement group_id="B2" value="6.0" spread="1.27"/>
                    <measurement group_id="B3" value="5.9" spread="1.24"/>
                  </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 randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 randomized participants.</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="173"/>
                <count group_id="O2" value="178"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="54"/>
                  </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 randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 randomized participants.</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="173"/>
                <count group_id="O2" value="178"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="76"/>
                  </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 randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 randomized participants.</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="173"/>
                <count group_id="O2" value="178"/>
              </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="170"/>
                    <count group_id="O2" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-8" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-7" upper_limit="3"/>
                  </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="173"/>
                    <count group_id="O2" value="169"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-7" upper_limit="1"/>
                    <measurement group_id="O2" value="-4.0" lower_limit="-8" upper_limit="3"/>
                  </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="172"/>
                    <count group_id="O2" value="177"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-7" upper_limit="2"/>
                    <measurement group_id="O2" value="-5.0" 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="173"/>
                    <count group_id="O2" value="178"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-8" upper_limit="2"/>
                    <measurement group_id="O2" value="-5.0" lower_limit="-8" upper_limit="1"/>
                  </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 included all participants in the ITT Population who achieved complete clearance at the Day 57 visit. 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 in a treatment area of 25 cm^2 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 included all participants in the ITT Population who achieved complete clearance at the Day 57 visit. 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="96"/>
              </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="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </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="70"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </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="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </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="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </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 set included 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 set included 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="173"/>
                <count group_id="O2" value="178"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Erythema-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81"/>
                    <measurement group_id="O2" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="111"/>
                  </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="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flaking/Scaling-Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148"/>
                    <measurement group_id="O2" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Crusting-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="30"/>
                  </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="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="169"/>
                    <measurement group_id="O2" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Swelling-Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="20"/>
                  </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="172"/>
                    <measurement group_id="O2" value="166"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vesiculation/Pustulation-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="11"/>
                  </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="0"/>
                  </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="171"/>
                    <measurement group_id="O2" value="156"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erosion/Ulceration-Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="18"/>
                  </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="4"/>
                  </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 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 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="173"/>
                <count group_id="O2" value="178"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hypopigmentation: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypopigmentation: Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperpigmentation: Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="11"/>
                  </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="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scarring: Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <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="10"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With 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 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 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="173"/>
                <count group_id="O2" value="178"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67"/>
                    <measurement group_id="O2" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with any SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <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="4"/>
                    <measurement group_id="O2" value="4"/>
                  </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 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. 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 included all participants in the ITT Population who 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 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. 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 included all participants in the ITT Population who 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="22"/>
                <count group_id="O2" value="97"/>
              </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="2"/>
                  </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="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="1"/>
                    <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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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="173"/>
                <count group_id="O2" value="178"/>
              </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="4"/>
                    <measurement group_id="O2" value="0"/>
                  </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="1"/>
                  </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 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 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="173"/>
                <count group_id="O2" value="178"/>
              </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 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 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="173"/>
                <count group_id="O2" value="178"/>
              </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 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 in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 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 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="173"/>
                <count group_id="O2" value="178"/>
              </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 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>Vehicle Ointment was applied topically once daily for 5 consecutive days in a treatment area of 25 cm^2 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 in a treatment area of 25 cm^2 on face or scalp.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="173"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </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="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="72" subjects_at_risk="173"/>
                <counts group_id="E2" subjects_affected="72" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Bowel movement irregularity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Food poisoning</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Tongue disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application site pruritus</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="173"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Application site pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="173"/>
                <counts group_id="E2" events="31" subjects_affected="24" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Application site inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Application site nodule</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Application site paraesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Application site scab</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Nodule</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="173"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="173"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Angular cheilitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Application site folliculitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Carbuncle</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Herpes simplex</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Labyrinthitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Onychomycosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Post procedural infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Pyuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Streptococcal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Subcutaneous abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Bacteriuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Animal bite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Face injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Tooth fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Blood testosterone decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Cardiac murmur</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Crystal urine present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Prostatic specific antigen increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Urobilinogen urine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Haemochromatosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="173"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Haemangioma of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Malignant melanoma in situ</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Melanocytic naevus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Renal cancer recurrent</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Seborrhoeic keratosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Skin papilloma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of head and neck</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Ketonuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </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="3" subjects_affected="3" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Actinic keratosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Lentigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Rosacea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Scab</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Skin tightness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Arthrodesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
              <event>
                <sub_title>Meniscus operation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="173"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="178"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>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/NCT03285490
org study id: KX01-AK-004
secondary id: U1111-1191-8287
nct id: NCT03285490
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This Phase III study was designed to evaluate the efficacy and safety of KX2-391 Ointment 1%
      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, efficacy, and safety study of KX2-391 ointment
      administered topically to the face or scalp of participants with AK.

      The study consisted of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods.
      Eligible participants received up to 5 consecutive days of topical treatment. Efficacy
      (lesion counts) and safety evaluations were 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 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. 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: KX2-391 Ointment 1%
arm group type: Experimental
description: KX2-391 Ointment was applied once daily for 5 consecutive days on the face or scalp.
arm group label: Placebo
arm group type: Placebo Comparator
description: The Vehicle Ointment was applied once daily for 5 consecutive days on the face or scalp.
intervention type: Drug
intervention name: KX2-391 Ointment 1%
description: Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical
arm group label: KX2-391 Ointment 1%
intervention type: Drug
intervention name: Placebo
description: Dosage form: Ointment; Route of administration: Topical
arm group label: Placebo
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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