<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/NCT02251652</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 13-0142</org_study_id>
    <nct_id>NCT02251652</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Ingenol Mebutate 0.05% Gel When Used After Cryotherapy in the Hypertrophic Actinic Keratoses</brief_title>
  <official_title>An Investigator-Initiated Study to Assess the Safety and Efficacy of Ingenol Mebutate 0.05% Gel When Used After Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses (AK) on Dorsal Hands</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>LEO Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sequential therapy with cryosurgery and ingenol mebutate may optimize the treatment of&#xD;
      hypertrophic AKs and also treat non-hypertrophic AKs in this anatomic location. Furthermore,&#xD;
      use of ingenol mebutate will also be evaluated for potential treatment of subclinical&#xD;
      lesions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to treat 30 subjects. Each qualifying subject will have at least 3&#xD;
      hypertrophic AKs, defined as more than 3mm in thickness, on each dorsal hand. Cryotherapy&#xD;
      will be standardized in all patients and for all treated lesions: 1-2 sprays, 5 seconds each,&#xD;
      with a 5 second interval. All subjects will be treated with the same cryo-spray. Following&#xD;
      cryotherapy, subjects will be randomized to treat either their right or left dorsal hand with&#xD;
      ingenol mebutate gel. The decision to treat the right vs. the left hand will be chosen by&#xD;
      chance, like flipping a coin. Neither the subject nor the study doctor will choose what arm&#xD;
      receives the ingenol mebutate gel. The study doctor will not know which arm is treated with&#xD;
      ingenol mebutate, so the subject should not reveal that information to him or her at any time&#xD;
      during the study. Subjects will treat the randomized dorsal hand with ingenol mebutate 0.05%&#xD;
      gel starting on the same day as the cryotherapy (Day 0). Subjects will utilize the once daily&#xD;
      for two days regimen. Subjects will be followed on day 4 after their initial visit, day 8,&#xD;
      day 15, day 29, and day 57, with a two day window period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2013</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of Combination Therapy vs Cryotherapy Alone</measure>
    <time_frame>Day 57</time_frame>
    <description>To evaluate the safety of cryotherapy plus ingenol mebutate on dorsal hands and compare it to the safety of cryotherapy alone looking at Adverse Events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Number of All Actinic Keratoses</measure>
    <time_frame>Baseline and Day 57</time_frame>
    <description>To evaluate and compare the mean reduction in number of all AKs (hypertrophic and non-hypertrophic) on the dorsal hands of the combination cryotherapy- ingenol mebutate treated side vs. the cryotherapy alone side on Day 57 as compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Actinic Keratoses by Anatomic Site</measure>
    <time_frame>Baseline and Day 57</time_frame>
    <description>To evaluate the number of AKs (both hypertrophic and non-hypertrophic) before therapy by anatomic site (dorsal hand) at Day 57 as compared to baseline</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Actinic Keratoses</condition>
  <arm_group>
    <arm_group_label>Combination Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cryotherapy followed by Ingenol Mebutate Gel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cryotherapy Alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cryotherapy only</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ingenol Mebutate</intervention_name>
    <description>Ingenol mebutate 0.05% gel</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <other_name>PEP005 Gel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cryotherapy</intervention_name>
    <description>1-2 sprays, 5 seconds each, with a 5 second interval</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <arm_group_label>Cryotherapy Alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults at least 18 years old.&#xD;
&#xD;
          -  Subjects must be in good general health as confirmed by the medical history.&#xD;
&#xD;
          -  Subjects must be able to read, sign, and understand the informed consent&#xD;
&#xD;
          -  Prior to cryosurgery, subjects have at least 3 hypertrophic actinic keratoses on each&#xD;
             dorsal hand.&#xD;
&#xD;
          -  Subject must be willing to forego any other treatments on the dorsum of the hands,&#xD;
             including tanning bed use and excessive sun exposure while in the study.&#xD;
&#xD;
          -  Subject is willing and able to participate in the study as an outpatient, making&#xD;
             frequent visits to the study center during the treatment and follow-up periods and to&#xD;
             comply with all study requirements including concomitant medication and other&#xD;
             treatment restrictions.&#xD;
&#xD;
          -  If subject is a female of childbearing potential she must have a negative urine&#xD;
             pregnancy test result prior to study treatment initiation and must agree to use an&#xD;
             approved method of birth control while enrolled in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of melanoma anywhere on the body.&#xD;
&#xD;
          -  Subjects with an unstable medical condition as deemed by the clinical investigator.&#xD;
&#xD;
          -  Subjects with non-melanoma skin cancer on the dorsum of the hands.&#xD;
&#xD;
          -  Subjects with any dermatologic disease in the treatment area that may be exacerbated&#xD;
             by the treatment proposed or that might impair the evaluation of AKs.&#xD;
&#xD;
          -  Subjects who have previously been treated with ingenol mebutate: on the dorsum of the&#xD;
             hands in the past 6 months; or outside of the study area within the past 30 days.&#xD;
&#xD;
          -  Women who are pregnant, lactating, or planning to become pregnant during the study&#xD;
             period.&#xD;
&#xD;
          -  Subjects who have experienced a clinically important medical event within 90 days of&#xD;
             the visit (e.g., stroke, myocardial infarction, etc).&#xD;
&#xD;
          -  Subjects who have active chemical dependency or alcoholism as assessed by the&#xD;
             investigator.&#xD;
&#xD;
          -  Subjects who have known allergies to any excipient in the study gel.&#xD;
&#xD;
          -  Subjects who are currently participating in another clinical study or have completed&#xD;
             another clinical study with an investigational drug or device on the study area within&#xD;
             30 days prior to study treatment initiation.&#xD;
&#xD;
          -  Subjects who have received any of the following within 90 days prior to study&#xD;
             treatment initiation:&#xD;
&#xD;
               -  interferon or interferon inducers&#xD;
&#xD;
               -  cytotoxic drugs&#xD;
&#xD;
               -  immunomodulators or immunosuppressive therapies (inhaled/ intranasal steroids are&#xD;
                  permitted)&#xD;
&#xD;
               -  oral or parenteral corticosteroids&#xD;
&#xD;
               -  topical corticosteroids if greater than 2 gm/day&#xD;
&#xD;
               -  any dermatologic procedures or surgeries on the study area (including any AK&#xD;
                  treatments)&#xD;
&#xD;
          -  Subjects who have used any topical prescription medications on the study area within&#xD;
             30 days prior to study treatment initiation.&#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>Gary Goldenberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>11370</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>March 15, 2017</results_first_submitted>
  <results_first_submitted_qc>March 15, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 26, 2017</results_first_posted>
  <last_update_submitted>March 15, 2017</last_update_submitted>
  <last_update_submitted_qc>March 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Gary Goldenberg</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Actinic</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>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited from the Faculty Practice and resident clinics at Mount Sinai. Seventeen subjects were enrolled in the study; one subject withdrew consent prior to treatment.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Actinic Keratosis</title>
          <description>Each subject is its own control - left dorsal hand compared to right dorsal hand</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Actinic Keratosis</title>
          <description>Each subject is its own control - left dorsal hand compared to right dorsal hand</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </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="67.06" spread="9.82"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety of Combination Therapy vs Cryotherapy Alone</title>
        <description>To evaluate the safety of cryotherapy plus ingenol mebutate on dorsal hands and compare it to the safety of cryotherapy alone looking at Adverse Events.</description>
        <time_frame>Day 57</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combination Therapy</title>
            <description>Cryotherapy followed by Ingenol Mebutate Gel&#xD;
Ingenol Mebutate: Ingenol mebutate 0.05% gel&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
          </group>
          <group group_id="O2">
            <title>Cryotherapy Alone</title>
            <description>Cryotherapy only&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
          </group>
        </group_list>
        <measure>
          <title>Safety of Combination Therapy vs Cryotherapy Alone</title>
          <description>To evaluate the safety of cryotherapy plus ingenol mebutate on dorsal hands and compare it to the safety of cryotherapy alone looking at Adverse Events.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </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>Change in Number of All Actinic Keratoses</title>
        <description>To evaluate and compare the mean reduction in number of all AKs (hypertrophic and non-hypertrophic) on the dorsal hands of the combination cryotherapy- ingenol mebutate treated side vs. the cryotherapy alone side on Day 57 as compared to baseline</description>
        <time_frame>Baseline and Day 57</time_frame>
        <population>Comparisons of proportion of responders between treated and control hands</population>
        <group_list>
          <group group_id="O1">
            <title>Combination Therapy</title>
            <description>Cryotherapy followed by Ingenol Mebutate Gel&#xD;
Ingenol Mebutate: Ingenol mebutate 0.05% gel&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
          </group>
          <group group_id="O2">
            <title>Cryotherapy Alone</title>
            <description>Cryotherapy only&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Number of All Actinic Keratoses</title>
          <description>To evaluate and compare the mean reduction in number of all AKs (hypertrophic and non-hypertrophic) on the dorsal hands of the combination cryotherapy- ingenol mebutate treated side vs. the cryotherapy alone side on Day 57 as compared to baseline</description>
          <population>Comparisons of proportion of responders between treated and control hands</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Actinic Keratoses lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Actinic Keratoses lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.6" spread="2.66"/>
                    <measurement group_id="O2" value="-2.5" spread="1.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Actinic Keratoses by Anatomic Site</title>
        <description>To evaluate the number of AKs (both hypertrophic and non-hypertrophic) before therapy by anatomic site (dorsal hand) at Day 57 as compared to baseline</description>
        <time_frame>Baseline and Day 57</time_frame>
        <population>Comparisons of proportion of responders between treated and control hands</population>
        <group_list>
          <group group_id="O1">
            <title>Combination Therapy</title>
            <description>Cryotherapy followed by Ingenol Mebutate Gel&#xD;
Ingenol Mebutate: Ingenol mebutate 0.05% gel&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
          </group>
          <group group_id="O2">
            <title>Cryotherapy Alone</title>
            <description>Cryotherapy only&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Actinic Keratoses by Anatomic Site</title>
          <description>To evaluate the number of AKs (both hypertrophic and non-hypertrophic) before therapy by anatomic site (dorsal hand) at Day 57 as compared to baseline</description>
          <population>Comparisons of proportion of responders between treated and control hands</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Actinic Keratoses lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Actinic Keratoses lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hypertrophic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-86.34" spread="16.642"/>
                    <measurement group_id="O2" value="-51.89" spread="19.091"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-hypertrophic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.1" spread="3.38"/>
                    <measurement group_id="O2" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Combination Therapy</title>
          <description>Cryotherapy followed by Ingenol Mebutate Gel&#xD;
Ingenol Mebutate: Ingenol mebutate 0.05% gel&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
        </group>
        <group group_id="E2">
          <title>Cryotherapy Alone</title>
          <description>Cryotherapy only&#xD;
Cryotherapy: 1-2 sprays, 5 seconds each, with a 5 second interval</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT 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>
    <limitations_and_caveats>Study limitations include small sample size and the fact that LSRs may unblind the investigator.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Gary Goldenberg</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-241-9728</phone>
      <email>garygoldenbergmd@gmail.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/NCT02251652
org study id: GCO 13-0142
nct id: NCT02251652
lead sponsor: 
collaborator: 
has dmc: Yes
Sequential therapy with cryosurgery and ingenol mebutate may optimize the treatment of
      hypertrophic AKs and also treat non-hypertrophic AKs in this anatomic location. Furthermore,
      use of ingenol mebutate will also be evaluated for potential treatment of subclinical
      lesions.
The investigators plan to treat 30 subjects. Each qualifying subject will have at least 3
      hypertrophic AKs, defined as more than 3mm in thickness, on each dorsal hand. Cryotherapy
      will be standardized in all patients and for all treated lesions: 1-2 sprays, 5 seconds each,
      with a 5 second interval. All subjects will be treated with the same cryo-spray. Following
      cryotherapy, subjects will be randomized to treat either their right or left dorsal hand with
      ingenol mebutate gel. The decision to treat the right vs. the left hand will be chosen by
      chance, like flipping a coin. Neither the subject nor the study doctor will choose what arm
      receives the ingenol mebutate gel. The study doctor will not know which arm is treated with
      ingenol mebutate, so the subject should not reveal that information to him or her at any time
      during the study. Subjects will treat the randomized dorsal hand with ingenol mebutate 0.05%
      gel starting on the same day as the cryotherapy (Day 0). Subjects will utilize the once daily
      for two days regimen. Subjects will be followed on day 4 after their initial visit, day 8,
      day 15, day 29, and day 57, with a two day window period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Safety of Combination Therapy vs Cryotherapy Alone
time frame: Day 57
description: To evaluate the safety of cryotherapy plus ingenol mebutate on dorsal hands and compare it to the safety of cryotherapy alone looking at Adverse Events.
measure: Change in Number of All Actinic Keratoses
time frame: Baseline and Day 57
description: To evaluate and compare the mean reduction in number of all AKs (hypertrophic and non-hypertrophic) on the dorsal hands of the combination cryotherapy- ingenol mebutate treated side vs. the cryotherapy alone side on Day 57 as compared to baseline
measure: Change in Actinic Keratoses by Anatomic Site
time frame: Baseline and Day 57
description: To evaluate the number of AKs (both hypertrophic and non-hypertrophic) before therapy by anatomic site (dorsal hand) at Day 57 as compared to baseline
arm group label: Combination Therapy
arm group type: Active Comparator
description: Cryotherapy followed by Ingenol Mebutate Gel
arm group label: Cryotherapy Alone
arm group type: Active Comparator
description: Cryotherapy only
intervention type: Drug
intervention name: Ingenol Mebutate
description: Ingenol mebutate 0.05% gel
arm group label: Combination Therapy
other name: PEP005 Gel
intervention type: Procedure
intervention name: Cryotherapy
description: 1-2 sprays, 5 seconds each, with a 5 second interval
arm group label: Combination Therapy
arm group label: Cryotherapy Alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gary Goldenberg, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Gary Goldenberg
investigator title: Assistant Professor
mesh term: Keratosis, Actinic
mesh term: Keratosis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study limitations include small sample size and the fact that LSRs may unblind the investigator.
point of contact: 