<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/NCT01670656</url>
  </required_header>
  <id_info>
    <org_study_id>P08257</org_study_id>
    <secondary_id>2012-002449-40</secondary_id>
    <secondary_id>MK-8175A/MK-8342B-057</secondary_id>
    <nct_id>NCT01670656</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effect of Contraceptive Vaginal Rings on Primary Dysmenorrhea (P08257/MK-8175A/MK-8342B-057)</brief_title>
  <official_title>A Multicenter, Randomized, Partially Blinded, Placebo-controlled Clinical Trial to Evaluate the Effect on Primary Dysmenorrhea of Vaginal Rings With an Average Daily Release of 700 μg Nomegestrol Acetate (NOMAC) and 300 μg Estradiol (E2), or 900 μg Nomegestrol Acetate (NOMAC) and 300 μg Estradiol (E2), or 100 μg Etonogestrel (ENG) and 300 μg E2, or 125 μg Etonogestrel (ENG) and 300 μg E2. Protocol MK-8175A/MK-8342B 057 (Abbreviated as P057), Also Known as SCH900121/SCH900432 08257 (Abbreviated as P08257)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Organon and Co</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Organon and Co</source>
  <oversight_info>
    <has_dmc>No</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 study investigates four vaginal ring groups with respect to relief of primary&#xD;
      dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant&#xD;
      treatment efficacy in relief of primary dysmenorrhea.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study investigates four vaginal ring groups with respect to relief of primary&#xD;
      dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant&#xD;
      treatment efficacy in relief of primary dysmenorrhea. The intake of ibuprofen rescue&#xD;
      medication and the impact on daily life is investigated: change from baseline data of these&#xD;
      two variables will be compared between each of the four active ring groups, separately, and&#xD;
      the placebo ring group. Furthermore, the study assesses the measurement characteristics and&#xD;
      psychometric properties of a newly developed Dysmenorrhea Daily Dairy. Vaginal bleeding&#xD;
      pattern and general safety and tolerability will also be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2013</start_date>
  <completion_date type="Actual">September 12, 2013</completion_date>
  <primary_completion_date type="Actual">September 11, 2013</primary_completion_date>
  <phase>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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2</measure>
    <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
    <description>The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: &quot;Cramps&quot;) in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total Mean Impact Score Through Cycle 2</measure>
    <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
    <description>Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being &quot;not at all&quot;, 1 &quot;slightly&quot;, 2 &quot;moderately&quot;, 3 &quot;quite a bit&quot; and 4 &quot;extremely&quot;. The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2</measure>
    <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
    <description>Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2</measure>
    <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
    <description>Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">439</enrollment>
  <condition>Dysmenorrhea</condition>
  <arm_group>
    <arm_group_label>NOMAC-E2 700/300 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NOMAC-E2 700/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NOMAC-E2 900/300 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NOMAC-E2 900/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ENG-E2 100/300 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ENG-E2 100/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ENG-E2 125/300 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ENG-E2 125/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)</intervention_name>
    <description>Either 700 or 900 mcg NOMAC and 300 mcg E2 intravaginal ring for two 28-day cycles</description>
    <arm_group_label>NOMAC-E2 700/300 mcg</arm_group_label>
    <arm_group_label>NOMAC-E2 900/300 mcg</arm_group_label>
    <other_name>SCH900121</other_name>
    <other_name>MK-8175A</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etonogestrel containing contraceptive vaginal ring (ENG-CVR)</intervention_name>
    <description>Either 100 or 125 mcg ENG and 300 mcg E2, intravaginally for two 28-day cycles</description>
    <arm_group_label>ENG-E2 100/300 mcg</arm_group_label>
    <arm_group_label>ENG-E2 125/300 mcg</arm_group_label>
    <other_name>SCH900432</other_name>
    <other_name>MK-8342B</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo to match vaginal ring, intravaginally for two 28-day cycles</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen</intervention_name>
    <description>Ibuprofen 400 mg will be dispensed throughout the entire study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose is 3200 mg (8 tablets)</description>
    <arm_group_label>ENG-E2 100/300 mcg</arm_group_label>
    <arm_group_label>ENG-E2 125/300 mcg</arm_group_label>
    <arm_group_label>NOMAC-E2 700/300 mcg</arm_group_label>
    <arm_group_label>NOMAC-E2 900/300 mcg</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Motrin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI) ≥18 and ≤35&#xD;
&#xD;
          -  Established diagnosis of primary dysmenorrhea&#xD;
&#xD;
          -  If of child-bearing potential must agree to use condoms for contraception during the&#xD;
             entire screening period, treatment period, and post-treatment period until the final&#xD;
             study visit, unless she or her partner are surgically sterilized&#xD;
&#xD;
          -  Agree to stop using hormonal contraceptive (combined or progestin-only), or a non&#xD;
             hormonal intrauterine device (IUD)&#xD;
&#xD;
          -  Regular menstrual cycles ranging from 24 to 35 days in length&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following contraindications to the use of contraceptive steroids including:&#xD;
             presence or a history of venous or arterial thrombotic/thromboembolic events or&#xD;
             cerebrovascular accident (stroke, history of migraine with focal neurological&#xD;
             symptoms, diabetes mellitus with vascular involvement, severe or multiple risk&#xD;
             factor(s) for venous or arterial thrombosis, severe dyslipoproteinemia, severe&#xD;
             hypertension, pancreatitis or a history thereof if associated with severe&#xD;
             hypertriglyceridaemia, presence or history of severe hepatic (liver) disease,&#xD;
             including benign or malignant tumors, known or suspected sex steroid-influenced&#xD;
             malignancies, and/or undiagnosed vaginal bleeding&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Secondary dysmenorrhea&#xD;
&#xD;
          -  Has not had spontaneous menstruation following a delivery or abortion&#xD;
&#xD;
          -  Participated in an investigational drug study within 30 days&#xD;
&#xD;
          -  History of malignancy ≤5 years&#xD;
&#xD;
          -  Documented abnormal cervical smear result within 6 months&#xD;
&#xD;
          -  Use of recreational or illicit drugs&#xD;
&#xD;
          -  Consumes &gt;2 alcoholic drinks per day or &gt;14 alcoholic drinks per week, or engages in&#xD;
             binge drinking&#xD;
&#xD;
          -  Allergy/sensitivity to ibuprofen, or any contraindication to its use, or has&#xD;
             experienced asthma, urticaria, or allergic-type reactions after taking aspirin, or&#xD;
             other nonsteroidal anti inflammatory drugs&#xD;
&#xD;
          -  Has been sterilized using a fallopian tube occlusion device&#xD;
&#xD;
          -  Is receiving, or has received sex hormones for any purpose other than contraception&#xD;
             within 2 months or injectable hormonal contraception within 6 months&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Norway</country>
    <country>Poland</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Sweden</country>
  </removed_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2012</study_first_posted>
  <results_first_submitted>July 25, 2017</results_first_submitted>
  <results_first_submitted_qc>July 25, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 24, 2017</results_first_posted>
  <last_update_submitted>February 2, 2022</last_update_submitted>
  <last_update_submitted_qc>February 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dysmenorrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibuprofen</mesh_term>
    <mesh_term>Contraceptive Agents</mesh_term>
    <mesh_term>Etonogestrel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NOMAC-E2 700/300 mcg</title>
          <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="P2">
          <title>NOMAC-E2 900/300 mcg</title>
          <description>NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="P3">
          <title>ENG-E2 100/300 mcg</title>
          <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="P4">
          <title>ENG-E2 125/300 mcg</title>
          <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="P5">
          <title>Placebo</title>
          <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="91"/>
                <participants group_id="P3" count="87"/>
                <participants group_id="P4" count="85"/>
                <participants group_id="P5" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="91"/>
                <participants group_id="P3" count="86"/>
                <participants group_id="P4" count="85"/>
                <participants group_id="P5" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="83"/>
                <participants group_id="P2" count="84"/>
                <participants group_id="P3" count="79"/>
                <participants group_id="P4" count="79"/>
                <participants group_id="P5" count="79"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Non-compliance with study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with protocol</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject withdrew consent</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject moved</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NOMAC-E2 700/300 mcg</title>
          <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="B2">
          <title>NOMAC-E2 900/300 mcg</title>
          <description>NOMAC-E2 900/300 mcg administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="B3">
          <title>ENG-E2 100/300 mcg</title>
          <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="B4">
          <title>ENG-E2 125/300 mcg</title>
          <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="B5">
          <title>Placebo</title>
          <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="86"/>
            <count group_id="B2" value="91"/>
            <count group_id="B3" value="87"/>
            <count group_id="B4" value="85"/>
            <count group_id="B5" value="90"/>
            <count group_id="B6" value="439"/>
          </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="28.7" spread="7.5"/>
                    <measurement group_id="B2" value="28.7" spread="8.1"/>
                    <measurement group_id="B3" value="29.0" spread="7.7"/>
                    <measurement group_id="B4" value="28.3" spread="7.8"/>
                    <measurement group_id="B5" value="28.4" spread="8.2"/>
                    <measurement group_id="B6" value="28.6" spread="7.8"/>
                  </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="86"/>
                    <measurement group_id="B2" value="91"/>
                    <measurement group_id="B3" value="87"/>
                    <measurement group_id="B4" value="85"/>
                    <measurement group_id="B5" value="90"/>
                    <measurement group_id="B6" value="439"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2</title>
        <description>The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: &quot;Cramps&quot;) in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe).</description>
        <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
        <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Menstrual Cramping Pain Score</population>
        <group_list>
          <group group_id="O1">
            <title>NOMAC-E2 700/300 mcg</title>
            <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O2">
            <title>NOMAC-E2 900/300 mcg</title>
            <description>NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O3">
            <title>ENG-E2 100/300 mcg</title>
            <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O4">
            <title>ENG-E2 125/300 mcg</title>
            <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2</title>
          <description>The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: &quot;Cramps&quot;) in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe).</description>
          <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Menstrual Cramping Pain Score</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="91"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" lower_limit="-2.0" upper_limit="-1.5"/>
                    <measurement group_id="O2" value="-1.7" lower_limit="-1.9" upper_limit="-1.5"/>
                    <measurement group_id="O3" value="-1.9" lower_limit="-2.1" upper_limit="-1.7"/>
                    <measurement group_id="O4" value="-1.7" lower_limit="-1.9" upper_limit="-1.5"/>
                    <measurement group_id="O5" value="-1.2" lower_limit="-1.4" upper_limit="-0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.0</ci_lower_limit>
            <ci_upper_limit>-0.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.9</ci_lower_limit>
            <ci_upper_limit>-0.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.1</ci_lower_limit>
            <ci_upper_limit>-0.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.9</ci_lower_limit>
            <ci_upper_limit>-0.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total Mean Impact Score Through Cycle 2</title>
        <description>Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being &quot;not at all&quot;, 1 &quot;slightly&quot;, 2 &quot;moderately&quot;, 3 &quot;quite a bit&quot; and 4 &quot;extremely&quot;. The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact).</description>
        <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
        <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Total Mean Impact Score</population>
        <group_list>
          <group group_id="O1">
            <title>NOMAC-E2 700/300 mcg</title>
            <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O2">
            <title>NOMAC-E2 900/300 mcg</title>
            <description>NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O3">
            <title>ENG-E2 100/300 mcg</title>
            <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O4">
            <title>ENG-E2 125/300 mcg</title>
            <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Mean Impact Score Through Cycle 2</title>
          <description>Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being &quot;not at all&quot;, 1 &quot;slightly&quot;, 2 &quot;moderately&quot;, 3 &quot;quite a bit&quot; and 4 &quot;extremely&quot;. The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact).</description>
          <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Total Mean Impact Score</population>
          <units>Units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.8" lower_limit="-5.6" upper_limit="-4.0"/>
                    <measurement group_id="O2" value="-5.0" lower_limit="-5.7" upper_limit="-4.2"/>
                    <measurement group_id="O3" value="-4.7" lower_limit="-5.5" upper_limit="-3.9"/>
                    <measurement group_id="O4" value="-4.3" lower_limit="-5.1" upper_limit="-3.5"/>
                    <measurement group_id="O5" value="-3.1" lower_limit="-3.9" upper_limit="-2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.002</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-1.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.0</ci_lower_limit>
            <ci_upper_limit>-0.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-1.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.1</ci_lower_limit>
            <ci_upper_limit>-0.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.003</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-1.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.9</ci_lower_limit>
            <ci_upper_limit>-0.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.024</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2</title>
        <description>Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.</description>
        <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
        <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Ibuprofen Tablets Taken</population>
        <group_list>
          <group group_id="O1">
            <title>NOMAC-E2 700/300 mcg</title>
            <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O2">
            <title>NOMAC-E2 900/300 mcg</title>
            <description>NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O3">
            <title>ENG-E2 100/300 mcg</title>
            <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O4">
            <title>ENG-E2 125/300 mcg</title>
            <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2</title>
          <description>Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.</description>
          <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Ibuprofen Tablets Taken</population>
          <units>Ibuprofen tablets</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="91"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.4" lower_limit="-7.5" upper_limit="-5.3"/>
                    <measurement group_id="O2" value="-6.3" lower_limit="-7.4" upper_limit="-5.2"/>
                    <measurement group_id="O3" value="-7.1" lower_limit="-8.2" upper_limit="-6.0"/>
                    <measurement group_id="O4" value="-6.0" lower_limit="-7.1" upper_limit="-4.9"/>
                    <measurement group_id="O5" value="-4.8" lower_limit="-6.0" upper_limit="-3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.026</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-1.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.4</ci_lower_limit>
            <ci_upper_limit>0.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.036</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.3</ci_lower_limit>
            <ci_upper_limit>0.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.002</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-2.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.1</ci_lower_limit>
            <ci_upper_limit>-0.5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.1</p_value>
            <method>cLDA</method>
            <param_type>Diffference in Least Squares Means</param_type>
            <param_value>-1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.0</ci_lower_limit>
            <ci_upper_limit>0.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2</title>
        <description>Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.</description>
        <time_frame>Baseline and Day 29 to 56 (Cycle 2)</time_frame>
        <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Days of Ibuprofen Intake</population>
        <group_list>
          <group group_id="O1">
            <title>NOMAC-E2 700/300 mcg</title>
            <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O2">
            <title>NOMAC-E2 900/300 mcg</title>
            <description>NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O3">
            <title>ENG-E2 100/300 mcg</title>
            <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O4">
            <title>ENG-E2 125/300 mcg</title>
            <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2</title>
          <description>Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.</description>
          <population>All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Days of Ibuprofen Intake</population>
          <units>Days of ibuprofen intake</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="91"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" lower_limit="-1.5" upper_limit="-1.0"/>
                    <measurement group_id="O2" value="-1.7" lower_limit="-2.0" upper_limit="-1.4"/>
                    <measurement group_id="O3" value="-1.7" lower_limit="-2.0" upper_limit="-1.4"/>
                    <measurement group_id="O4" value="-1.4" lower_limit="-1.7" upper_limit="-1.1"/>
                    <measurement group_id="O5" value="-1.1" lower_limit="-1.4" upper_limit="-0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.447</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.6</ci_lower_limit>
            <ci_upper_limit>0.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.003</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.0</ci_lower_limit>
            <ci_upper_limit>-0.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.003</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.0</ci_lower_limit>
            <ci_upper_limit>-0.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>= 0.156</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least Squares Means</param_type>
            <param_value>-0.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>0.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 64 days</time_frame>
      <desc>The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.</desc>
      <group_list>
        <group group_id="E1">
          <title>NOMAC-E2 (700/300 mcg)</title>
          <description>NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days</description>
        </group>
        <group group_id="E2">
          <title>NOMAC-E2 (900/300 mcg)</title>
          <description>NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="E3">
          <title>ENG-E2 (100/300 mcg)</title>
          <description>ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="E4">
          <title>ENG-E2 (125/300 mcg)</title>
          <description>ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
        <group group_id="E5">
          <title>Placebo</title>
          <description>Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Impulse-control disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="91"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="86"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="85"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="86"/>
                <counts group_id="E2" events="19" subjects_affected="9" subjects_at_risk="91"/>
                <counts group_id="E3" events="13" subjects_affected="11" subjects_at_risk="86"/>
                <counts group_id="E4" events="7" subjects_affected="5" subjects_at_risk="85"/>
                <counts group_id="E5" events="9" subjects_affected="7" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="7" subjects_affected="5" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator agrees to provide to the Sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including slides and texts of oral or other public presentations and texts of any transmission through any electronic media that report results of the trial. The Sponsor has the right to review and comment with respect to publications, abstracts, slides, and manuscripts, as wells as comment on the data analysis and presentation.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT01670656
org study id: P08257
secondary id: 2012-002449-40
secondary id: MK-8175A/MK-8342B-057
nct id: NCT01670656
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study investigates four vaginal ring groups with respect to relief of primary
      dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant
      treatment efficacy in relief of primary dysmenorrhea.
The study investigates four vaginal ring groups with respect to relief of primary
      dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant
      treatment efficacy in relief of primary dysmenorrhea. The intake of ibuprofen rescue
      medication and the impact on daily life is investigated: change from baseline data of these
      two variables will be compared between each of the four active ring groups, separately, and
      the placebo ring group. Furthermore, the study assesses the measurement characteristics and
      psychometric properties of a newly developed Dysmenorrhea Daily Dairy. Vaginal bleeding
      pattern and general safety and tolerability will also be evaluated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2
time frame: Baseline and Day 29 to 56 (Cycle 2)
description: The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: "Cramps") in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe).
measure: Change From Baseline in Total Mean Impact Score Through Cycle 2
time frame: Baseline and Day 29 to 56 (Cycle 2)
description: Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being "not at all", 1 "slightly", 2 "moderately", 3 "quite a bit" and 4 "extremely". The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact).
measure: Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2
time frame: Baseline and Day 29 to 56 (Cycle 2)
description: Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.
measure: Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2
time frame: Baseline and Day 29 to 56 (Cycle 2)
description: Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries.
arm group label: NOMAC-E2 700/300 mcg
arm group type: Experimental
description: NOMAC-E2 700/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
arm group label: NOMAC-E2 900/300 mcg
arm group type: Experimental
description: NOMAC-E2 900/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
arm group label: ENG-E2 100/300 mcg
arm group type: Experimental
description: ENG-E2 100/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
arm group label: ENG-E2 125/300 mcg
arm group type: Experimental
description: ENG-E2 125/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
intervention type: Drug
intervention name: Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR)
description: Either 700 or 900 mcg NOMAC and 300 mcg E2 intravaginal ring for two 28-day cycles
arm group label: NOMAC-E2 700/300 mcg
arm group label: NOMAC-E2 900/300 mcg
other name: SCH900121
other name: MK-8175A
intervention type: Drug
intervention name: Etonogestrel containing contraceptive vaginal ring (ENG-CVR)
description: Either 100 or 125 mcg ENG and 300 mcg E2, intravaginally for two 28-day cycles
arm group label: ENG-E2 100/300 mcg
arm group label: ENG-E2 125/300 mcg
other name: SCH900432
other name: MK-8342B
intervention type: Drug
intervention name: Placebo
description: Placebo to match vaginal ring, intravaginally for two 28-day cycles
arm group label: Placebo
intervention type: Drug
intervention name: Ibuprofen
description: Ibuprofen 400 mg will be dispensed throughout the entire study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose is 3200 mg (8 tablets)
arm group label: ENG-E2 100/300 mcg
arm group label: ENG-E2 125/300 mcg
arm group label: NOMAC-E2 700/300 mcg
arm group label: NOMAC-E2 900/300 mcg
arm group label: Placebo
other name: Motrin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Australia
country: Belgium
country: Chile
country: Colombia
country: Denmark
country: Germany
country: Mexico
country: Netherlands
country: New Zealand
country: Norway
country: Poland
country: South Africa
country: Spain
country: Sweden
responsible party type: Sponsor
mesh term: Dysmenorrhea
mesh term: Ibuprofen
mesh term: Contraceptive Agents
mesh term: Etonogestrel
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 