<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/NCT03024502</url>
  </required_header>
  <id_info>
    <org_study_id>03.12.0056.00</org_study_id>
    <secondary_id>2013/50496-2</secondary_id>
    <nct_id>NCT03024502</nct_id>
  </id_info>
  <brief_title>Patients With Vulvovaginal Candidiasis</brief_title>
  <acronym>EPP-AFG-VVC</acronym>
  <official_title>Randomized Clinical Trial of a Mucoadhesive Gel Containing EPP-AF in Patients Diagnosed With Vulvovaginal Candidiasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study aims to evaluate the safety of two mucoadhesive gels containing a propolis&#xD;
      standardized extract identified as EPP-AF, with 1 and 2% of propolis. The efficacy studies&#xD;
      with both propolis gels will be performed in comparison with clotrimazole cream in patients&#xD;
      presenting vulvovaginal candidiasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vaginal candidiasis is the second infection of the genital tract after bacterial vaginosis.&#xD;
      Up to 75% of women will have at least one episode in their lives, but the clinical&#xD;
      manifestations can be very variable. Around 10 to 20% will be asymptomatic and 5 to 10% will&#xD;
      have the recurrent candidiasis that means 4 or more episodes in a year. The predominant&#xD;
      symptoms are pruritus in 89% and burning during urination and sexual intercourse in 66%. The&#xD;
      therapeutic regimen for acute fungal infections by C. albicans should consider the intensity&#xD;
      of the clinical symptoms, recurrence, patient preference for the route of administration and&#xD;
      consequent adherence to treatment, presence of pregnancy and the possibility of side effects.&#xD;
      In general, the schemes include anti-fungal substances of the azoles type. Intravaginal&#xD;
      administration of drugs requires the development of formulations suited to the area and&#xD;
      adherence to the treatment can be increased if mucoadhesive formulations are obtained which&#xD;
      avoid discomfort and provide adequate release of the active compounds. In this sense, the&#xD;
      present project had the objective of developing a mucoadhesive gel containing Propolis&#xD;
      Standardized (EPP-AF®) for the treatment of vaginal candidiasis, especially since preclinical&#xD;
      efficacy and safety data demonstrated the clinical potential of the product. So the present&#xD;
      proposal aims at the clinical study evaluate the efficacy of two formulations with 1 and 2%&#xD;
      of propolis in comparison with clotrimazole cream treatment (patients affected by&#xD;
      Candidiasis) and also evaluate the safety of both propolis gels in healthy volunteers. The&#xD;
      efficacy protocol of the test product in patients with vaginal candidiasis will be performed&#xD;
      in an open-label, randomized, three-arm, clinical trial with active clotrimazole-based&#xD;
      control. Patients will be recruited (T0) and evaluated at 10 and 30 days after initiation of&#xD;
      treatment, and the primary outcome will be the clinical cure rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 30, 2018</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">January 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</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>clinical cure</measure>
    <time_frame>10 days</time_frame>
    <description>Participants will be evaluated on the tenth day after insertion in the study (on the third day after the termination of the vaginal cream). The clinical cure will be evaluated by means of a questionnaire and specular examination. The possibilities will be:&#xD;
Candidacy Resolution&#xD;
No resolution of candidiasis&#xD;
The questionnaire will be:&#xD;
Pruritus: yes or no Burning: yes or no Dysuria: yes or no Edema of the genital area: yes or no Running: yes or no&#xD;
The specular examination will evaluate:&#xD;
Presence of hyperemia: yes or no Edema of the genital area: yes or no Presence of cracks: yes or no Pathological vaginal contents: yes or no The positive response to any of the questions or signs / symptoms will be considered as clinical failure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>microbiology cure</measure>
    <time_frame>10 days</time_frame>
    <description>Participants will be evaluated on the tenth day after insertion in the study (on the third day after the termination of the vaginal cream). The patient's clinical complaint will be evaluated and the specular examination will be performed. In this evaluation will be collected the following exams:&#xD;
Vaginal pH measurement:&#xD;
Normal 3.5 to 4.5 Abnormal&gt; 4.5&#xD;
Bacterioscopy with KOH10%:&#xD;
Normal: absence of pseudohifas or other pathogenic elements Abnormal: presence of pseudohifas&#xD;
Culture for candida albicans:&#xD;
Normal: Negative Abnormal: positive&#xD;
PCR for candida:&#xD;
Normal negative Abnormal: positive&#xD;
The possibilities will be:&#xD;
Candidacy Resolution&#xD;
No resolution of candidiasis It will be considered microbiological cure when all laboratory tests are considered normal</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Vulvovaginal Candidiasis</condition>
  <arm_group>
    <arm_group_label>EPP-AF Gel 1%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients that will be treated with EPP-AF mucoadhesive gel 1%, during 7 day, 1x/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clotrimazole cream</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients that will be treated with clotrimazole cream, during 7 day, 1x/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EPP-AF Gel 2%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients that will be treated with EPP-AF mucoadhesive gel 2%, during 7 day, 1x/day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EPP-AF Gel 1%</intervention_name>
    <description>Administration intravaginal of EPP-AG Gel 1%, 1x/day, 7 days</description>
    <arm_group_label>EPP-AF Gel 1%</arm_group_label>
    <other_name>Drug 1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EPP-AF Gel 2%</intervention_name>
    <description>Administration intravaginal of EPP-AG Gel 1%, 1x/day, 7 days</description>
    <arm_group_label>EPP-AF Gel 2%</arm_group_label>
    <other_name>Drug 2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clotrimazole</intervention_name>
    <description>Administration intravaginal of clotrimazol, 1x/day, 7 days</description>
    <arm_group_label>Clotrimazole cream</arm_group_label>
    <other_name>Active Comparator</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -Have performed the clinical and laboratory diagnosis of vulvovaginitis by Candida&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cPatients with recurrent candidiasis;&#xD;
&#xD;
          -  History of hepatic, renal, hematological, cardiovascular diseases and with&#xD;
             decompensated diabetes mellitus (glycemia above 200) and obesity with BMI above 35);&#xD;
&#xD;
          -  Diagnosis of vulvovaginitis by another agent;&#xD;
&#xD;
          -  Make use of chronic antimicrobials (informed by the patient)&#xD;
&#xD;
          -  Be pregnant&#xD;
&#xD;
          -  Allergy to some component of medications given&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>silvana m quintana, phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sao Paulo University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>silvana ma quintana, phd</last_name>
    <phone>5516981459112</phone>
    <email>quintana@fmrp.usp.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>anderson silva, phd</last_name>
    <phone>551636021000</phone>
    <email>asssilva@fmrp.usp.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Clinical Hospital of Sao Paulo University</name>
      <address>
        <city>Ribeirao Preto</city>
        <state>Sao Paulo</state>
        <zip>14049-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Larissa B Bastos, MSc</last_name>
      <phone>+55017988034386</phone>
      <email>larissabbastos4@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>October 17, 2018</last_update_submitted>
  <last_update_submitted_qc>October 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Silvana Maria Quintana</investigator_full_name>
    <investigator_title>clinical professor and principal investigator</investigator_title>
  </responsible_party>
  <keyword>vulvovaginal candidiasis</keyword>
  <keyword>EPPAF mucoadhesive gel</keyword>
  <keyword>clotrimazol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Candidiasis</mesh_term>
    <mesh_term>Candidiasis, Vulvovaginal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clotrimazole</mesh_term>
    <mesh_term>Miconazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03024502
org study id: 03.12.0056.00
secondary id: 2013/50496-2
nct id: NCT03024502
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The present study aims to evaluate the safety of two mucoadhesive gels containing a propolis
      standardized extract identified as EPP-AF, with 1 and 2% of propolis. The efficacy studies
      with both propolis gels will be performed in comparison with clotrimazole cream in patients
      presenting vulvovaginal candidiasis.
Vaginal candidiasis is the second infection of the genital tract after bacterial vaginosis.
      Up to 75% of women will have at least one episode in their lives, but the clinical
      manifestations can be very variable. Around 10 to 20% will be asymptomatic and 5 to 10% will
      have the recurrent candidiasis that means 4 or more episodes in a year. The predominant
      symptoms are pruritus in 89% and burning during urination and sexual intercourse in 66%. The
      therapeutic regimen for acute fungal infections by C. albicans should consider the intensity
      of the clinical symptoms, recurrence, patient preference for the route of administration and
      consequent adherence to treatment, presence of pregnancy and the possibility of side effects.
      In general, the schemes include anti-fungal substances of the azoles type. Intravaginal
      administration of drugs requires the development of formulations suited to the area and
      adherence to the treatment can be increased if mucoadhesive formulations are obtained which
      avoid discomfort and provide adequate release of the active compounds. In this sense, the
      present project had the objective of developing a mucoadhesive gel containing Propolis
      Standardized (EPP-AF®) for the treatment of vaginal candidiasis, especially since preclinical
      efficacy and safety data demonstrated the clinical potential of the product. So the present
      proposal aims at the clinical study evaluate the efficacy of two formulations with 1 and 2%
      of propolis in comparison with clotrimazole cream treatment (patients affected by
      Candidiasis) and also evaluate the safety of both propolis gels in healthy volunteers. The
      efficacy protocol of the test product in patients with vaginal candidiasis will be performed
      in an open-label, randomized, three-arm, clinical trial with active clotrimazole-based
      control. Patients will be recruited (T0) and evaluated at 10 and 30 days after initiation of
      treatment, and the primary outcome will be the clinical cure rate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: clinical cure
time frame: 10 days
description: Participants will be evaluated on the tenth day after insertion in the study (on the third day after the termination of the vaginal cream). The clinical cure will be evaluated by means of a questionnaire and specular examination. The possibilities will be:
Candidacy Resolution
No resolution of candidiasis
The questionnaire will be:
Pruritus: yes or no Burning: yes or no Dysuria: yes or no Edema of the genital area: yes or no Running: yes or no
The specular examination will evaluate:
Presence of hyperemia: yes or no Edema of the genital area: yes or no Presence of cracks: yes or no Pathological vaginal contents: yes or no The positive response to any of the questions or signs / symptoms will be considered as clinical failure
measure: microbiology cure
time frame: 10 days
description: Participants will be evaluated on the tenth day after insertion in the study (on the third day after the termination of the vaginal cream). The patient's clinical complaint will be evaluated and the specular examination will be performed. In this evaluation will be collected the following exams:
Vaginal pH measurement:
Normal 3.5 to 4.5 Abnormal> 4.5
Bacterioscopy with KOH10%:
Normal: absence of pseudohifas or other pathogenic elements Abnormal: presence of pseudohifas
Culture for candida albicans:
Normal: Negative Abnormal: positive
PCR for candida:
Normal negative Abnormal: positive
The possibilities will be:
Candidacy Resolution
No resolution of candidiasis It will be considered microbiological cure when all laboratory tests are considered normal
arm group label: EPP-AF Gel 1%
arm group type: Experimental
description: Group of patients that will be treated with EPP-AF mucoadhesive gel 1%, during 7 day, 1x/day.
arm group label: Clotrimazole cream
arm group type: Experimental
description: Group of patients that will be treated with clotrimazole cream, during 7 day, 1x/day.
arm group label: EPP-AF Gel 2%
arm group type: Experimental
description: Group of patients that will be treated with EPP-AF mucoadhesive gel 2%, during 7 day, 1x/day.
intervention type: Drug
intervention name: EPP-AF Gel 1%
description: Administration intravaginal of EPP-AG Gel 1%, 1x/day, 7 days
arm group label: EPP-AF Gel 1%
other name: Drug 1
intervention type: Drug
intervention name: EPP-AF Gel 2%
description: Administration intravaginal of EPP-AG Gel 1%, 1x/day, 7 days
arm group label: EPP-AF Gel 2%
other name: Drug 2
intervention type: Drug
intervention name: Clotrimazole
description: Administration intravaginal of clotrimazol, 1x/day, 7 days
arm group label: Clotrimazole cream
other name: Active Comparator
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: silvana m quintana, phd
role: Principal Investigator
affiliation: Sao Paulo University
last name: silvana ma quintana, phd
phone: 5516981459112
email: quintana@fmrp.usp.br
last name: anderson silva, phd
phone: 551636021000
email: asssilva@fmrp.usp.br
facility: 
status: Recruiting
contact: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Silvana Maria Quintana
investigator title: clinical professor and principal investigator
mesh term: Candidiasis
mesh term: Candidiasis, Vulvovaginal
mesh term: Clotrimazole
mesh term: Miconazole
sharing ipd: No