<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/NCT02215395</url>
  </required_header>
  <id_info>
    <org_study_id>571</org_study_id>
    <nct_id>NCT02215395</nct_id>
  </id_info>
  <brief_title>An Open-label Study to Evaluate the Effects of Concurrent Administration of Vaginal Antimycotic Medication Miconazole Nitrate on the Pharmacokinetics of Nestorone and Ethinyl Estradiol Delivered by a Contraceptive Vaginal Ring in Normal Ovulating Women</brief_title>
  <official_title>Phase 1, Open-label Study to Evaluate the Effects of Concurrent Administration of Vaginal Antimycotic Medication (Miconazole Nitrate) on the Pharmacokinetics of Nestorone and Ethinyl Estradiol Delivered by a Contraceptive Vaginal Ring Releasing a Daily Dose of 150 ug of NES and 15 ug of EE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Population Council</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Population Council</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the pharmacokinetics (PK) of EE and NES released from the CVR in the presence of&#xD;
      a single dose and multiple doses of antimycotic co-medication (miconazole nitrate suppository&#xD;
      or cream).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Drug Drug Interaction of NES/EE CVR and topical anti-fungal medication</measure>
    <time_frame>Week 12</time_frame>
    <description>To evaluate adverse reactions to a topical anti-fungal medication when used in conjunction with the NES/EE CVR</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Antifungal Drug Adverse Reaction</condition>
  <arm_group>
    <arm_group_label>CVR treatment cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women who meet all inclusion and no exclusion criteria will be randomized to the first treatment cycle with the CVR alone followed by the second treatment cycle with the CVR and miconazole (one of three dosing regimens) or the first treatment cycle with the CVR and miconazole followed by the second treatment cycle with the CVR alone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NES/EE CVR</intervention_name>
    <description>Concurrent administration of vaginal antimycotic medication (Miconazole Nitrate) on the pharmacokinetics of Nestorone (NES) and ethinyl estradiol (EE) delivered by a contraceptive vaginal ring (CVR)</description>
    <arm_group_label>CVR treatment cycle</arm_group_label>
    <other_name>Nestorone (NES) and ethinyl estradiol (EE) delivered by a contraceptive vaginal ring (CVR)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy women, inclusive of ages 18-35* years at the enrollment visit&#xD;
&#xD;
          -  Intact uterus and both ovaries&#xD;
&#xD;
          -  Prior history of regular menstrual cycles that usually occur every 28 ± 7 days when&#xD;
             not using hormonal contraception; if postpartum or post-abortal, history of regular&#xD;
             menstrual cycles of 21-35 days in length and resumption of at least one cycle with a&#xD;
             cycle length consistent with her past cycles&#xD;
&#xD;
          -  In the opinion of the investigator, able to comply with the protocol, e.g. live within&#xD;
             the study site catchment area or within a reasonable distance from the study site&#xD;
&#xD;
          -  May be sterilized or at risk of becoming pregnant&#xD;
&#xD;
          -  Willing to use a non-hormonal method of contraception for one month prior to the&#xD;
             initial insertion of the NES/EE CVR and the one month washout period&#xD;
&#xD;
          -  Willing to abstain from sexual intercourse during the miconazole nitrate treatment&#xD;
             period(s)&#xD;
&#xD;
          -  Signed informed consent prior to entry into the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to estrogens or progestins&#xD;
&#xD;
          -  Pregnant, trying to become pregnant, or breastfeeding&#xD;
&#xD;
          -  Known hypersensitivity to silicone rubber&#xD;
&#xD;
          -  Undiagnosed abnormal vaginal bleeding&#xD;
&#xD;
          -  Undiagnosed vaginal discharge, vaginal lesions or abnormalities. Subjects diagnosed at&#xD;
             screening with a Chlamydia or gonococcus infection may be included in the trial&#xD;
             following treatment; partner treatment is also recommended. Investigators should make&#xD;
             a determination if subjects are at high risk for reinfection, e.g., multiple sex&#xD;
             partners, untreated partner, and whether such subjects can be included&#xD;
&#xD;
          -  History of pelvic inflammatory disease since the subject's last pregnancy&#xD;
&#xD;
          -  History of toxic shock syndrome&#xD;
&#xD;
          -  In accordance with the Bethesda system of classification: Women with a current (within&#xD;
             the last 20 months) abnormal Pap smear suggestive of high-grade pre-cancerous lesion&#xD;
             (s), including HGSIL&#xD;
&#xD;
          -  Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a&#xD;
             vaginal ring&#xD;
&#xD;
          -  Women planning to undergo major surgery during the trial&#xD;
&#xD;
          -  Women who smoke 15 cigarettes or more per day must be evaluated by the PI for&#xD;
             inclusion based on risk factors that would increase their risk for cardiovascular&#xD;
             disease and thromboembolism, e.g., lipid levels, glucose level, BP, BMI, family&#xD;
             history of cardiovascular disease at a young age&#xD;
&#xD;
          -  Current or past thrombophlebitis or thromboembolic disorders&#xD;
&#xD;
          -  History of venous thrombosis or embolism in a first-degree relative, &lt;55 years of age&#xD;
             suggesting a familial defect in the blood coagulation system, which in the opinion of&#xD;
             the PI, suggests that use of a hormonal contraceptive could pose a significant risk&#xD;
&#xD;
          -  Cerebrovascular or cardiovascular disease&#xD;
&#xD;
          -  History of retinal vascular lesions, unexplained partial or complete loss of vision&#xD;
&#xD;
          -  Known or suspected carcinoma of the breast&#xD;
&#xD;
          -  Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia&#xD;
&#xD;
          -  Past history of any other carcinoma unless in remission for more than five years&#xD;
&#xD;
          -  Current or history of medically diagnosed severe depression, which, in the opinion of&#xD;
             the investigator, could be exacerbated by the use of a hormonal contraceptive&#xD;
&#xD;
          -  Headaches with focal neurological symptoms&#xD;
&#xD;
          -  Severe constipation in the opinion of the investigator&#xD;
&#xD;
          -  History of cholestatic jaundice of pregnancy or jaundice with prior steroid use&#xD;
&#xD;
          -  Benign or malignant liver tumors; active liver disease&#xD;
&#xD;
          -  Diastolic blood pressure (BP) &gt;85 mm Hg and/or systolic BP &gt;135 mm Hg after 5-10&#xD;
             minutes rest (at screening)&#xD;
&#xD;
          -  Known or suspected alcoholism or drug abuse within their lifetime&#xD;
&#xD;
          -  Elevated serum fasting clinical chemistry values or complete blood count (CBC) values&#xD;
             designated clinically significant by the investigator and/or medically qualified&#xD;
             sub-investigator&#xD;
&#xD;
          -  Screening hemoglobin levels less than 12.5 g/dL or hematocrit less than 38%.&#xD;
&#xD;
          -  Participation in another clinical trial involving an investigational drug within the&#xD;
             last 30 days (prior to screening)&#xD;
&#xD;
          -  BMI &gt;29&#xD;
&#xD;
          -  Use of liver enzyme inducers on a regular basis&#xD;
&#xD;
          -  Use of monthly injectable contraceptives, unless suspended 2 months before initiation&#xD;
             of the treatment. Use of Depo-Provera [depo-medroxyprogesterone (DMPA)] unless&#xD;
             suspended 6 months before treatment&#xD;
&#xD;
          -  Current use of implanted hormonal contraceptives, including Mirena [progestin&#xD;
             containing intrauterine system (IUS)], Jadelle, Norplant, Implanon or Nexplanon (if&#xD;
             now available in the USA).**&#xD;
&#xD;
          -  Known HIV, Hepatitis B or Hepatitis C infection&#xD;
&#xD;
          -  History of frequent vaginal infections in the opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dennis Morrison, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>QPS-Biokinetic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>QPS Bio-Kinetic</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65802</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>May 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 11, 2017</last_update_submitted>
  <last_update_submitted_qc>August 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nestorone</keyword>
  <keyword>miconazole nitrate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ethinyl Estradiol</mesh_term>
    <mesh_term>Contraceptive Agents</mesh_term>
    <mesh_term>Estradiol</mesh_term>
  </intervention_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/NCT02215395
org study id: 571
nct id: NCT02215395
lead sponsor: 
has dmc: No
To evaluate the pharmacokinetics (PK) of EE and NES released from the CVR in the presence of
      a single dose and multiple doses of antimycotic co-medication (miconazole nitrate suppository
      or cream).
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Drug Drug Interaction of NES/EE CVR and topical anti-fungal medication
time frame: Week 12
description: To evaluate adverse reactions to a topical anti-fungal medication when used in conjunction with the NES/EE CVR
arm group label: CVR treatment cycle
arm group type: Experimental
description: Women who meet all inclusion and no exclusion criteria will be randomized to the first treatment cycle with the CVR alone followed by the second treatment cycle with the CVR and miconazole (one of three dosing regimens) or the first treatment cycle with the CVR and miconazole followed by the second treatment cycle with the CVR alone.
intervention type: Drug
intervention name: NES/EE CVR
description: Concurrent administration of vaginal antimycotic medication (Miconazole Nitrate) on the pharmacokinetics of Nestorone (NES) and ethinyl estradiol (EE) delivered by a contraceptive vaginal ring (CVR)
arm group label: CVR treatment cycle
other name: Nestorone (NES) and ethinyl estradiol (EE) delivered by a contraceptive vaginal ring (CVR)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Dennis Morrison, MD
role: Principal Investigator
affiliation: QPS-Biokinetic
facility: 
country: United States
responsible party type: Sponsor
mesh term: Drug-Related Side Effects and Adverse Reactions
mesh term: Ethinyl Estradiol
mesh term: Contraceptive Agents
mesh term: Estradiol