xml: <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/NCT05994599</url>
    </required_header>
    <id_info>
      <org_study_id>EVE-P6-604</org_study_id>
      <nct_id>NCT05994599</nct_id>
    </id_info>
    <brief_title>Comparative Bioavailability Study of Ethinyl Estradiol/Etonogestrel Vaginal Ring</brief_title>
    <official_title>SINGLE DOSE CROSSOVER COMPARATIVE BIOAVAILABILITY STUDY OF ETHINYL ESTRADIOL/ETONOGESTREL VAGINAL RING (DELIVERING 0.015 mg/0.12 mg PER DAY) WORN FOR 21 DAYS IN HEALTHY FEMALE SUBJECTS</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Evestra Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Evestra Inc.</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>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Single Dose Crossover Comparative Bioavailability Study of Ethinyl Estradiol/Etonogestrel&#xD;
        Vaginal Ring (Delivering 0.015 mg/0.12 mg Per Day) Worn for 21 Days in Healthy Female&#xD;
        Subjects&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 28, 2023</start_date>
    <completion_date type="Anticipated">November 21, 2023</completion_date>
    <primary_completion_date type="Anticipated">November 21, 2023</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>Crossover Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Laboratory Blinded</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Bioequivalence: evaluate and compare the bioavailability and therefore to assess the bioequivalence of 2 different formulations of ethinyl estradiol/etonogestrel vaginal ring</measure>
      <time_frame>Up to 24 days post ring insertion per period</time_frame>
      <description>The primary study endpoints are the pharmacokinetic (PK) parameter is the Cmax.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Bioequivalence: evaluate and compare the bioavailability and therefore to assess the bioequivalence of 2 different formulations of ethinyl estradiol/etonogestrel vaginal ring</measure>
      <time_frame>Up to 24 days post ring insertion per period</time_frame>
      <description>The primary study endpoints are the pharmacokinetic (PK) parameter is AUC0-T of ethinyl estradiol and etonogestrel.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Bioequivalence: evaluate and compare the bioavailability and therefore to assess the bioequivalence of 2 different formulations of ethinyl estradiol/etonogestrel vaginal ring</measure>
      <time_frame>Up to 24 days post ring insertion per period</time_frame>
      <description>The primary study endpoints are the pharmacokinetic (PK) parameter is and AUC0-∞ of ethinyl estradiol and etonogestrel.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety and tolerability of the vaginal rings</measure>
      <time_frame>through study completion, expected 102 days</time_frame>
      <description>Incidence and severity of treatment emergent adverse events (TEAEs) and serious TEAEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evaluate the vaginal local irritation and occurrence of bleeding/spotting</measure>
      <time_frame>through study completion, expected 102 days</time_frame>
      <description>Assessment of vaginal irritation and occurrence of bleeding/spotting through subject questionnaire/diary.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Healthy Women</condition>
    <condition>Female</condition>
    <condition>Contraception</condition>
    <arm_group>
      <arm_group_label>EVE119 vaginal ring</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>EVE119 (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Nuvaring vaginal ring</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Nuvaring® (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>EVE119 vaginal ring</intervention_name>
      <description>EVE119 (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day</description>
      <arm_group_label>EVE119 vaginal ring</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Nuvaring vaginal ring</intervention_name>
      <description>Nuvaring® (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day</description>
      <arm_group_label>Nuvaring vaginal ring</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provision of signed and dated Informed Consent Form (ICF)&#xD;
  &#xD;
            2. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study&#xD;
  &#xD;
            3. Healthy adult female&#xD;
  &#xD;
            4. Meets 1 of the following criteria:&#xD;
  &#xD;
                 1. Is of childbearing potential and agrees to use an acceptable contraceptive&#xD;
                    method. Acceptable contraceptive methods include:&#xD;
  &#xD;
                      -  Abstinence from heterosexual intercourse from the Screening visit through to&#xD;
                         at least 28 days after the last vaginal ring removal&#xD;
  &#xD;
                      -  The following double-barrier contraceptive methods, used from the Screening&#xD;
                         visit through to at least 28 days after the last vaginal ring removal:&#xD;
  &#xD;
                           -  Male condom with spermicide Or&#xD;
  &#xD;
                 2. Is of non-childbearing potential, defined as surgically sterile (ie, tubal&#xD;
                    ligation)&#xD;
  &#xD;
            5. Aged at least 18 years but not older than 45 years in pre-menopausal state&#xD;
  &#xD;
            6. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively&#xD;
  &#xD;
            7. Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using&#xD;
               nicotine products for at least 180 days prior to the first vaginal ring insertion)&#xD;
  &#xD;
            8. Normal pap test result on file at Altasciences in the previous 12 months prior to the&#xD;
               first vaginal ring insertion or normal pap test result at Screening&#xD;
  &#xD;
            9. Have no clinically significant diseases captured in the medical history or evidence of&#xD;
               clinically significant findings on the physical examination (including breast and&#xD;
               gynecological examination) and/or electrocardiogram (ECG), as determined by an&#xD;
               Investigator&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Female who is lactating&#xD;
  &#xD;
            2. Female who is pregnant according to the pregnancy test at Screening or prior to the&#xD;
               first vaginal ring insertion&#xD;
  &#xD;
            3. Use of the following systemic contraceptives: oral, patch, or vaginal ring, in the 28&#xD;
               days prior to the first vaginal insertion and until completion of the study&#xD;
  &#xD;
            4. Use of hormone replacement therapy in the 28 days prior to the first vaginal insertion&#xD;
               and until completion of the study&#xD;
  &#xD;
            5. Use of the following systemic contraceptives: injections or implant, or&#xD;
               hormone-releasing intrauterine device (IUD) in the 13 weeks prior to the first vaginal&#xD;
               insertion and until completion of the study&#xD;
  &#xD;
            6. Has contraindication for contraceptive steroids&#xD;
  &#xD;
            7. Post-menopausal status (minimum of a year without menses) and/or has undergone a&#xD;
               complete hysterectomy or bilateral oophorectomy&#xD;
  &#xD;
            8. Seated blood pressure higher than 140/90 mmHg at the Screening visit and prior to the&#xD;
               first vaginal ring insertion, unless deemed non-significant by an Investigator&#xD;
  &#xD;
            9. History of significant hypersensitivity to ethinyl estradiol, etonogestrel, or any&#xD;
               related products (including excipients of the formulations) as well as severe&#xD;
               hypersensitivity reactions (like angioedema) to any drugs&#xD;
  &#xD;
           10. Presence or history of significant genital, gastrointestinal, liver or kidney disease,&#xD;
               or any other condition that is known to interfere with drug absorption, distribution,&#xD;
               metabolism or excretion, or known to potentiate or predispose to undesired effects&#xD;
  &#xD;
           11. History of significant cardiovascular, pulmonary, hematologic, neurological,&#xD;
               psychiatric, endocrine, immunologic, or dermatologic disease, as defined by the&#xD;
               Investigator&#xD;
  &#xD;
           12. Presence of clinically significant ECG abnormalities at the Screening visit, as&#xD;
               defined by the Investigator&#xD;
  &#xD;
           13. Known presence or history of thrombophlebitis or any thromboembolic disorders (eg,&#xD;
               venous thrombosis, arterial thrombosis), with or without pulmonary embolism&#xD;
  &#xD;
           14. Known predisposition for venous or arterial thrombosis, with or without hereditary&#xD;
               involvement such as Activated Protein C-resistance (including Factor V Leiden),&#xD;
               antithrombin-III deficiency, protein C deficiency, protein S deficiency,&#xD;
               hyperhomocysteinemia, and antiphospholipid antibodies (anticardiolipin antibodies,&#xD;
               lupus anticoagulant)&#xD;
  &#xD;
           15. Known presence or history of classic migraine&#xD;
  &#xD;
           16. Known presence of ocular lesion arising from ophthalmic vascular disease, such as&#xD;
               partial or complete loss of vision or defect in visual fields&#xD;
  &#xD;
           17. Known presence, suspected presence or history of cervical, breast, uterine,&#xD;
               estrogen-dependent, or progestin-dependent cancer or other sex-steroid sensitive&#xD;
               malignancies&#xD;
  &#xD;
           18. Known presence or history of undiagnosed abnormal vaginal bleeding&#xD;
  &#xD;
           19. Known presence of any condition that makes the use of the vaginal ring difficult such&#xD;
               as prolapse of the uterine cervix, cystocele, and/or rectocele, severe or chronic&#xD;
               constipation&#xD;
  &#xD;
           20. Any other vaginal condition that would interfere with the vaginal ring or cause an&#xD;
               increased health risk&#xD;
  &#xD;
           21. Scheduled immunization with a Coronavirus Disease 2019 (COVID-19) vaccine during the&#xD;
               study that, in the opinion of an Investigator, could potentially interfere with&#xD;
               subject participation, subject safety, study results, or any other reason&#xD;
  &#xD;
           22. Major surgery with prolonged immobilisation in the previous 6 months prior to the&#xD;
               first vaginal ring insertion&#xD;
  &#xD;
           23. Planned major elective surgery in the 3 months following removal of the vaginal ring&#xD;
  &#xD;
           24. Maintenance therapy with any drug or significant history of drug dependency or alcohol&#xD;
               abuse (&gt; 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)&#xD;
  &#xD;
           25. Any clinically significant illness in the 28 days prior to the first vaginal ring&#xD;
               insertion&#xD;
  &#xD;
           26. Use of any prescription drugs in the 28 days prior to the first vaginal ring&#xD;
               insertion, that in the opinion of an Investigator would put into question the status&#xD;
               of the participant as healthy&#xD;
  &#xD;
           27. Use of St. John's wort in the 28 days prior to the first vaginal ring insertion&#xD;
  &#xD;
           28. Any history of tuberculosis&#xD;
  &#xD;
           29. Positive test result for alcohol and/or drugs of abuse at Screening or prior to the&#xD;
               first vaginal ring insertion&#xD;
  &#xD;
           30. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen, or&#xD;
               hepatitis C virus tests&#xD;
  &#xD;
           31. Serum ferritin value below 24 μg/L at Screening&#xD;
  &#xD;
           32. Any other clinically significant abnormalities in laboratory test results at Screening&#xD;
               that would, in the opinion of an Investigator, increase the subject's risk of&#xD;
               participation, jeopardize complete participation in the study, or compromise&#xD;
               interpretation of study data&#xD;
  &#xD;
           33. Inclusion in a previous group for this clinical study&#xD;
  &#xD;
           34. Intake of ethinyl estradiol or etonogestrel in the 28 days prior to the first vaginal&#xD;
               ring insertion&#xD;
  &#xD;
           35. Intake of an IP in the 28 days prior to the first vaginal ring insertion&#xD;
  &#xD;
           36. Donation of 50 mL or more of blood in the 28 days prior to the first vaginal ring&#xD;
               insertion&#xD;
  &#xD;
           37. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical&#xD;
               studies, etc.) in the 56 days prior to the first vaginal ring insertion&#xD;
  &#xD;
           38. Hemoglobin laboratory values below the lower limit of the reference at Screening -&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ze'ev Shaked, PhD</last_name>
      <role>Study Director</role>
      <affiliation>Evestra CEO</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ze'ev Shaked, PhD</last_name>
      <phone>210-673-3300</phone>
      <email>E119clinicaltrial@evestra.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Altasciences</name>
        <address>
          <city>Mount Royal</city>
          <state>Quebec</state>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Eric Sicard, MD</last_name>
      </contact>
      <investigator>
        <last_name>Eric Sicard, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>NuvaRing</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05994599
  org study id: EVE-P6-604
  nct id: NCT05994599
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  Single Dose Crossover Comparative Bioavailability Study of Ethinyl Estradiol/Etonogestrel
        Vaginal Ring (Delivering 0.015 mg/0.12 mg Per Day) Worn for 21 Days in Healthy Female
        Subjects
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Prevention
  masking: Single (Outcomes Assessor)
  masking description: Laboratory Blinded
  measure: Bioequivalence: evaluate and compare the bioavailability and therefore to assess the bioequivalence of 2 different formulations of ethinyl estradiol/etonogestrel vaginal ring
  time frame: Up to 24 days post ring insertion per period
  description: The primary study endpoints are the pharmacokinetic (PK) parameter is the Cmax.
  measure: Bioequivalence: evaluate and compare the bioavailability and therefore to assess the bioequivalence of 2 different formulations of ethinyl estradiol/etonogestrel vaginal ring
  time frame: Up to 24 days post ring insertion per period
  description: The primary study endpoints are the pharmacokinetic (PK) parameter is AUC0-T of ethinyl estradiol and etonogestrel.
  measure: Bioequivalence: evaluate and compare the bioavailability and therefore to assess the bioequivalence of 2 different formulations of ethinyl estradiol/etonogestrel vaginal ring
  time frame: Up to 24 days post ring insertion per period
  description: The primary study endpoints are the pharmacokinetic (PK) parameter is and AUC0-∞ of ethinyl estradiol and etonogestrel.
  measure: Safety and tolerability of the vaginal rings
  time frame: through study completion, expected 102 days
  description: Incidence and severity of treatment emergent adverse events (TEAEs) and serious TEAEs
  measure: Evaluate the vaginal local irritation and occurrence of bleeding/spotting
  time frame: through study completion, expected 102 days
  description: Assessment of vaginal irritation and occurrence of bleeding/spotting through subject questionnaire/diary.
  arm group label: EVE119 vaginal ring
  arm group type: Experimental
  description: EVE119 (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day
  arm group label: Nuvaring vaginal ring
  arm group type: Active Comparator
  description: Nuvaring® (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day
  intervention type: Combination Product
  intervention name: EVE119 vaginal ring
  description: EVE119 (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day
  arm group label: EVE119 vaginal ring
  intervention type: Combination Product
  intervention name: Nuvaring vaginal ring
  description: Nuvaring® (ethinyl estradiol/etonogestrel) vaginal ring delivering 0.015 mg/0.12 mg dose per day
  arm group label: Nuvaring vaginal ring
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Ze'ev Shaked, PhD
  role: Study Director
  affiliation: Evestra CEO
  last name: Ze'ev Shaked, PhD
  phone: 210-673-3300
  email: E119clinicaltrial@evestra.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: Canada
  responsible party type: Sponsor
  mesh term: NuvaRing
  sharing ipd: No