<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/NCT02242747</url>
  </required_header>
  <id_info>
    <org_study_id>11334</org_study_id>
    <nct_id>NCT02242747</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability Study of Ingenol Mebutate Compared to 5-FU to Treat Facial Actinic Keratosis</brief_title>
  <official_title>Evaluation of the Tolerability and Safety of 0.015% Ingenol Mebutate Gel Compared to 5% 5-fluorouracil Cream for the Treatment of Facial Actinic Keratosis: a Prospective Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>LEO Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: 5% 5-fluorouracil cream (5-FU) is a well-established treatment for actinic&#xD;
      keratosis (AK) and ingenol mebutate gel (IMB) is a new topical field therapy.&#xD;
&#xD;
      Objective: To compare tolerability and safety of IMB with 5-FU for the treatment of facial&#xD;
      AKs.&#xD;
&#xD;
      Methods: Open-label, prospective, randomized, controlled clinical trial with 100 patients&#xD;
      with AKs within 25-cm2 contiguous field on the face. IMB was applied daily for three&#xD;
      consecutive days. 5-FU was applied twice a day for four weeks. Treatment effect was evaluated&#xD;
      at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43, considering ITT populations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the LSR (local skin reactions)-Time Curve (AUC 0-43 days)</measure>
    <time_frame>Baseline and on day 43</time_frame>
    <description>Primary endpoint was to compare the total local skin reaction grading scale (LSR) and the area under the curve (AUC) with respect to duration of effects, using a generalized linear model, assuming a logarithmic link function. Age, Fitzpatrick skin type and site of the treatment were considered as covariates. The scale ranged from 0 to 4 (with higher numbers indicating greater severity) for the following six local skin effects: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration (maximum score of 24).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the each component of the total LSR-Time Curve (AUC 0-43 days)</measure>
    <time_frame>Baseline and on day 43</time_frame>
    <description>A secondary endpoint was to evaluate and compare the AUC for each component of the total LSR using generalized linear models. The effect of treatment on the proportion of patients that completed the assigned treatment regimens was compared using generalized estimating equation model and logarithmic link function.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of participants with side effects in each arm of the study</measure>
    <time_frame>Baseline and on day 43</time_frame>
    <description>An additional endpoint was to evaluate adverse effects related to the drugs.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Actinic Keratosis</condition>
  <arm_group>
    <arm_group_label>ingenol mebutate</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients assigned to ingenol mebutate gel received an application a day for three consecutive days in a pre-determined area</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5% 5-FU</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients assigned to 5% 5-FU received two applications a day for four weeks in a pre-determined area</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ingenol mebutate</intervention_name>
    <description>an application a day for three consecutive days in a pre-determined area</description>
    <arm_group_label>ingenol mebutate</arm_group_label>
    <other_name>Picato</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5% 5-FU</intervention_name>
    <description>two applications a day for four weeks in a pre-determined area</description>
    <arm_group_label>5% 5-FU</arm_group_label>
    <other_name>efurix</other_name>
    <other_name>efudex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age of at least 18 years&#xD;
&#xD;
          -  the presence of four to eight clinically typical, visible, and discrete AKs within&#xD;
             25-cm2 contiguous field on the face (cheek or forehead region)&#xD;
&#xD;
          -  Women with childbearing potential had to be using effective birth control and have a&#xD;
             confirmed negative urine pregnancy test prior to trial treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  target treatment area was within 5 cm of an incompletely healed wound or within 10 cm&#xD;
             of a suspected basal-cell or squamous-cell carcinoma&#xD;
&#xD;
          -  if they have received previous treatment with ingenol mebutate gel on the face or&#xD;
             scalp (previous treatment on trunk or extremities was acceptable)&#xD;
&#xD;
          -  the selected treatment area had hyperkeratotic lesions or cutaneous horns and&#xD;
             recalcitrant disease (lesions that had not responded to cryotherapy on two previous&#xD;
             occasions)&#xD;
&#xD;
          -  history or evidence of skin conditions that would interfere with the evaluation of the&#xD;
             trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)&#xD;
&#xD;
          -  anticipated need for hospitalization or outpatient surgery during the first 15 days&#xD;
             after the first trial medication application&#xD;
&#xD;
          -  known sensitivity or allergy to any of the ingredients of ingenol mebutate gel or 5-FU&#xD;
&#xD;
          -  presence of sunburn within of the target treatment area; current enrolment or&#xD;
             participation in any other interventional clinical trial within 30 days of entry into&#xD;
             this trial&#xD;
&#xD;
          -  women breastfeeding&#xD;
&#xD;
          -  recent use of medications or other treatments that could interfere with evaluation of&#xD;
             the target area, such as topical medications (e.g. steroids, keratolytics,&#xD;
             immunomodulators), artificial tanners, immunomodulators, cytotoxic drugs or interferon&#xD;
             /interferon inducers, phototherapy, systemic retinoids, biologic/monoclonal antibody&#xD;
             drugs, or other therapies for AKs within eight weeks prior to the first visit of the&#xD;
             trial.&#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>Luis Antonio Torezan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>September 15, 2014</last_update_submitted>
  <last_update_submitted_qc>September 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 17, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Luis Antonio Torezan</investigator_full_name>
    <investigator_title>Associate Professor University of Sao Paulo</investigator_title>
  </responsible_party>
  <keyword>actinic keratosis</keyword>
  <keyword>field cancerization</keyword>
  <keyword>ingenol mebutate</keyword>
  <keyword>5-fluorouracil</keyword>
  <keyword>tolerability</keyword>
  <keyword>safety</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>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02242747
org study id: 11334
nct id: NCT02242747
lead sponsor: 
collaborator: 
has dmc: Yes
Background: 5% 5-fluorouracil cream (5-FU) is a well-established treatment for actinic
      keratosis (AK) and ingenol mebutate gel (IMB) is a new topical field therapy.

      Objective: To compare tolerability and safety of IMB with 5-FU for the treatment of facial
      AKs.

      Methods: Open-label, prospective, randomized, controlled clinical trial with 100 patients
      with AKs within 25-cm2 contiguous field on the face. IMB was applied daily for three
      consecutive days. 5-FU was applied twice a day for four weeks. Treatment effect was evaluated
      at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43, considering ITT populations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the LSR (local skin reactions)-Time Curve (AUC 0-43 days)
time frame: Baseline and on day 43
description: Primary endpoint was to compare the total local skin reaction grading scale (LSR) and the area under the curve (AUC) with respect to duration of effects, using a generalized linear model, assuming a logarithmic link function. Age, Fitzpatrick skin type and site of the treatment were considered as covariates. The scale ranged from 0 to 4 (with higher numbers indicating greater severity) for the following six local skin effects: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration (maximum score of 24).
measure: Area Under the each component of the total LSR-Time Curve (AUC 0-43 days)
time frame: Baseline and on day 43
description: A secondary endpoint was to evaluate and compare the AUC for each component of the total LSR using generalized linear models. The effect of treatment on the proportion of patients that completed the assigned treatment regimens was compared using generalized estimating equation model and logarithmic link function.
measure: Number of participants with side effects in each arm of the study
time frame: Baseline and on day 43
description: An additional endpoint was to evaluate adverse effects related to the drugs.
arm group label: ingenol mebutate
arm group type: Other
description: Patients assigned to ingenol mebutate gel received an application a day for three consecutive days in a pre-determined area
arm group label: 5% 5-FU
arm group type: Other
description: Patients assigned to 5% 5-FU received two applications a day for four weeks in a pre-determined area
intervention type: Drug
intervention name: ingenol mebutate
description: an application a day for three consecutive days in a pre-determined area
arm group label: ingenol mebutate
other name: Picato
intervention type: Drug
intervention name: 5% 5-FU
description: two applications a day for four weeks in a pre-determined area
arm group label: 5% 5-FU
other name: efurix
other name: efudex
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Luis Antonio Torezan, PhD
role: Principal Investigator
affiliation: Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Luis Antonio Torezan
investigator title: Associate Professor University of Sao Paulo
mesh term: Keratosis, Actinic
mesh term: Keratosis