<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/NCT01710514</url>
  </required_header>
  <id_info>
    <org_study_id>000072</org_study_id>
    <nct_id>NCT01710514</nct_id>
  </id_info>
  <brief_title>A Phase III Study of FE 999913 in Japanese Female Patients Undergoing Fertility Treatment</brief_title>
  <official_title>A Multi-Center, Randomized, Open-Label, Parallel Group Study of FE 999913 Vaginal Tablet 100 mg in Japanese Female Patients Undergoing Fertility Treatment [In Vitro Fertilization/Embryo Transfer (IVF-ET)]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ferring Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ferring Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purposes of the study are to verify sufficient supplementation of luteal hormone after&#xD;
      administrating FE999913 Vaginal Tablet twice a day (BID) or three times a day (TID) and to&#xD;
      determine the efficacy and safety of FE999913 Vaginal Tablet in Japanese women undergoing&#xD;
      fertility treatment with IVF-ET (a fresh embryo transfer).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Proportion of Subjects With Blood Progesterone Concentration Not Less Than 10 ng/ml</measure>
    <time_frame>Day 5 of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ongoing Pregnancy Rate</measure>
    <time_frame>Week 5 of study</time_frame>
    <description>Defined as identification of fetal survival and fetal heart movements on transvaginal ultrasound</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of Positive βeta Human Chorionic Gonadotrophin (βhCG)</measure>
    <time_frame>Week 2 of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Pregnancy Rate</measure>
    <time_frame>Week 4 of study</time_frame>
    <description>Defined as presence of a gestational sac on transvaginal ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Progesterone Concentration</measure>
    <time_frame>Weeks 2, 4, 5, 8, and end of study</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">108</enrollment>
  <condition>Luteal Hormone Supplementation</condition>
  <arm_group>
    <arm_group_label>FE 999913 100 mg BID</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>FE 999913 100 mg vaginal tablet BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FE 999913 100 mg TID</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>FE 999913 100 mg vaginal tablet TID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FE 999913 vaginal tablet</intervention_name>
    <arm_group_label>FE 999913 100 mg BID</arm_group_label>
    <arm_group_label>FE 999913 100 mg TID</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pre-menopausal adult women between the ages of 20 and 42 years.&#xD;
&#xD;
          -  Early follicular phase (day 2-4) follicle stimulating hormone (FSH) ≤12 IU/L and&#xD;
             Estradiol &lt;100 pg/mL.&#xD;
&#xD;
          -  Luteinizing hormone (LH), prolactin (PRL), and thyroid-stimulating hormone (TSH),&#xD;
             within the normal limits for the clinical laboratory tests, or considered not&#xD;
             clinically significant by the investigator within 6 months prior to screening.&#xD;
&#xD;
          -  Documented history of infertility [e.g., unable to conceive for at least one year (or&#xD;
             for 6 months for women ≥38 years of age) or bilateral tubal occlusion or absence].&#xD;
&#xD;
          -  Transvaginal ultrasound at screening (or within 14 days prior to screening) consistent&#xD;
             with findings adequate for Assisted Reproduction Technology (ART) with respect to&#xD;
             uterus and adnexa (peripheral reproductive organs).&#xD;
&#xD;
          -  At least one cycle with no fertility medication prior to screening.&#xD;
&#xD;
          -  Hysterosalpingography, hysteroscopy, sonohysterogram, or transvaginal ultrasound&#xD;
             documenting a normal uterine cavity.&#xD;
&#xD;
          -  Consent to contraception during the cycle in which pituitary down regulation is&#xD;
             performed (prior to start of controlled ovarian stimulation).&#xD;
&#xD;
          -  Signed informed consent to fertility treatment using FE999913 Vaginal Tablet after the&#xD;
             subject and her husband have thoroughly understood the content.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Donor oocyte or embryo recipient; gestational or surrogate carrier.&#xD;
&#xD;
          -  Undergoing blastomer biopsy and other experimental ART procedures.&#xD;
&#xD;
          -  Severe hepatic dysfunction or disease.&#xD;
&#xD;
          -  Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of&#xD;
             these events.&#xD;
&#xD;
          -  Porphyria.&#xD;
&#xD;
          -  Presence of any clinically relevant systemic disease (eg, insulin-dependent diabetes&#xD;
             mellitus).&#xD;
&#xD;
          -  Past or current surgical or medical condition which in the judgment of the Principal&#xD;
             Investigator (or Sub-investigator) may interfere with absorption, distribution,&#xD;
             metabolism, or excretion of the study drug.&#xD;
&#xD;
          -  Subjects with a body mass index (BMI) of &gt;34 at time of Screening.&#xD;
&#xD;
          -  Previous IVF or ART failure due to a poor response to gonadotropins*.&#xD;
&#xD;
             * Defined as development of ≤2 mature follicles or history of 2 previous cycle&#xD;
             cancellations prior to oocyte retrieval due to poor response.&#xD;
&#xD;
          -  Presence of abnormal uterine bleeding of undetermined origin.&#xD;
&#xD;
          -  Current or recent (within the past 12 months) substance abuse, including alcohol.&#xD;
&#xD;
          -  Known or suspected breast or genital tract cancer.&#xD;
&#xD;
          -  History of chemotherapy or radiotherapy for malignant disorder (chorionic disease).&#xD;
&#xD;
          -  Currently breast feeding, pregnant or contraindication to pregnancy.&#xD;
&#xD;
          -  Refusal or inability to comply with the requirements of the Protocol for any reason,&#xD;
             including scheduled visits and clinical laboratory tests.&#xD;
&#xD;
          -  Documented intolerance or allergy to any of the medications to be used in the study&#xD;
             including the investigational medicinal product.&#xD;
&#xD;
          -  Participation in any experimental drug study within 60 days prior to Screening.&#xD;
&#xD;
          -  Use of any of the following medications during the pretreatment and treatment phase:&#xD;
             hormonal drug products (use of oral contraceptives prior to start of controlled&#xD;
             ovarian stimulation is allowed), other progesterone drug products, hydrocortisone and&#xD;
             other steroid drug products, and fertility modifiers such as insulin sensitizers.&#xD;
&#xD;
          -  History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>42 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Development Support</last_name>
    <role>Study Director</role>
    <affiliation>Ferring Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hanabusa Women's Clinic</name>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ebina Ladies Clinic</name>
      <address>
        <city>Ebina</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sophia Ladies Clinic</name>
      <address>
        <city>Sagamihara</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bashamichi Ladies Clinic</name>
      <address>
        <city>Yokohama</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IVF Namba Clinic</name>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanno Hospital</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 19, 2012</study_first_posted>
  <results_first_submitted>July 11, 2014</results_first_submitted>
  <results_first_submitted_qc>August 15, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 19, 2014</results_first_posted>
  <last_update_submitted>August 29, 2014</last_update_submitted>
  <last_update_submitted_qc>August 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 5, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>FE 999913 100 mg BID</title>
          <description>FE 999913 100 mg vaginal tablet BID&#xD;
FE 999913 vaginal tablet</description>
        </group>
        <group group_id="P2">
          <title>FE 999913 100 mg TID</title>
          <description>FE 999913 100 mg vaginal tablet TID&#xD;
FE 999913 vaginal tablet</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="54"/>
                <participants group_id="P2" count="54"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Intent-To-Treat (ITT) Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="54">All randomised subjects were included in the Intent-To-Treat (ITT) analysis set.</participants>
                <participants group_id="P2" count="54">All randomised subjects were included in the ITT analysis set.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="46">All randomised and exposed subjects with at least one completed primary efficacy assessment.</participants>
                <participants group_id="P2" count="48">All randomised and exposed subjects with at least one completed primary efficacy assessment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>FAS With Embryo Transfer (ET)</title>
              <participants_list>
                <participants group_id="P1" count="43">Data on pregnancy was reported for the subjects with embryo transfer.</participants>
                <participants group_id="P2" count="47">Data on pregnancy was reported for the subjects with embryo transfer.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="54">All subjects received at least one dose of Investigational Medicinal Product (IMP).</participants>
                <participants group_id="P2" count="54">All subjects received at least one dose of IMP.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </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="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full Analysis Set (FAS) population</population>
      <group_list>
        <group group_id="B1">
          <title>FE 999913 100 mg BID</title>
          <description>FE 999913 100 mg vaginal tablet BID</description>
        </group>
        <group group_id="B2">
          <title>FE 999913 100 mg TID</title>
          <description>FE 999913 100 mg vaginal tablet TID</description>
        </group>
        <group group_id="B3">
          <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="46"/>
            <count group_id="B2" value="48"/>
            <count group_id="B3" value="94"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>FAS population</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.9" spread="3.6"/>
                    <measurement group_id="B2" value="34.5" spread="4.25"/>
                    <measurement group_id="B3" value="34.7" spread="3.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <description>FAS population</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;35 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>35-37 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>38-40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>41-42 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>FAS population</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="94"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="94"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Day of transfer</title>
          <description>FAS with embryo transfer (ET) (BID: 43, TID: 47, Total: 90)</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Subjects with embryo transferred</title>
          <description>FAS with ET (BID: 43, TID: 47, Total: 90)</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>1 embryo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 embryos</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Embryos transferred</title>
          <description>FAS with ET (BID: 43, TID: 47, Total: 90)</description>
          <units>embryos</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.09" spread="0.294"/>
                    <measurement group_id="B2" value="1.11" spread="0.312"/>
                    <measurement group_id="B3" value="1.1" spread="0.302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Method of insemination</title>
          <description>FAS with ET (BID: 43, TID: 47, Total: 90)</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>IVF</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intracytoplasmic Sperm Injection (ICSI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Proportion of Subjects With Blood Progesterone Concentration Not Less Than 10 ng/ml</title>
        <time_frame>Day 5 of treatment</time_frame>
        <population>FAS population</population>
        <group_list>
          <group group_id="O1">
            <title>FE999913 000072 (BID/TID)</title>
            <description>Data pooled from both BID and TID groups</description>
          </group>
        </group_list>
        <measure>
          <title>The Proportion of Subjects With Blood Progesterone Concentration Not Less Than 10 ng/ml</title>
          <population>FAS population</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.9" lower_limit="94.2" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>To verify sufficient supplementation of luteal hormone, the proportion of subjects with blood progesterone concentration ≥ 10 ng/mL on Day 5 was compared to the result from a historical control, trial CS08 (NCT number: 00884221). The corresponding proportion of subjects in trial CS08 was 99.8% (95%CI: 99.1;100.0, 631/632 subjects). The non-inferiority hypothesis tested for this primary endpoint was: H0: P(000072)-P(CS08) ≤ -10.0% against the alternative Ha: P(000072)-P(CS08) &gt; -10.0%.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The null hypothesis (H0) was tested against the alternative (Ha) by constructing two-sided 95%CI for the difference. The non-inferiority limit for the difference was pre-specified to -10.0% (absolute). If the lower limit of the two-sided 95%CI was greater than the non-inferiority limit (-10.0%) for both the FAS and per protocol set, the null hypothesis was to be rejected. In that case it would be claimed that the rate observed in this trial was non-inferior to the rate observed in the CS08 trial</non_inferiority_desc>
            <param_type>Difference of % to historical control</param_type>
            <param_value>-0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.6</ci_lower_limit>
            <ci_upper_limit>1.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Ongoing Pregnancy Rate</title>
        <description>Defined as identification of fetal survival and fetal heart movements on transvaginal ultrasound</description>
        <time_frame>Week 5 of study</time_frame>
        <population>FAS with ET population</population>
        <group_list>
          <group group_id="O1">
            <title>FE 999913 100 mg BID</title>
            <description>FE 999913 100 mg vaginal tablet BID</description>
          </group>
          <group group_id="O2">
            <title>FE 999913 100 mg TID</title>
            <description>FE 999913 100 mg vaginal tablet TID</description>
          </group>
          <group group_id="O3">
            <title>FE 999913 Total</title>
            <description>Data pooled from BID and TID groups</description>
          </group>
        </group_list>
        <measure>
          <title>Ongoing Pregnancy Rate</title>
          <description>Defined as identification of fetal survival and fetal heart movements on transvaginal ultrasound</description>
          <population>FAS with ET population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.0" lower_limit="5.3" upper_limit="27.9"/>
                    <measurement group_id="O2" value="29.8" lower_limit="17.3" upper_limit="44.9"/>
                    <measurement group_id="O3" value="22.2" lower_limit="14.1" upper_limit="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Positive βeta Human Chorionic Gonadotrophin (βhCG)</title>
        <time_frame>Week 2 of study</time_frame>
        <population>FAS with ET population In the TID group 13 subjects had a positive beta-hCG assessment while 14 subjects had a positive clinical pregnancy at Week 4. This is because one subject had a negative beta-hCG at Week 2, but she had a positive local serum hCG on the same day and continued the trial. Then clinical and ongoing pregnancy were confirmed.</population>
        <group_list>
          <group group_id="O1">
            <title>FE 999913 100 mg BID</title>
            <description>FE 999913 100 mg vaginal tablet BID</description>
          </group>
          <group group_id="O2">
            <title>FE 999913 100 mg TID</title>
            <description>FE 999913 100 mg vaginal tablet TID</description>
          </group>
          <group group_id="O3">
            <title>FE 999913 Total</title>
            <description>Data pooled from BID and TID groups</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Positive βeta Human Chorionic Gonadotrophin (βhCG)</title>
          <population>FAS with ET population In the TID group 13 subjects had a positive beta-hCG assessment while 14 subjects had a positive clinical pregnancy at Week 4. This is because one subject had a negative beta-hCG at Week 2, but she had a positive local serum hCG on the same day and continued the trial. Then clinical and ongoing pregnancy were confirmed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.3" lower_limit="6.8" upper_limit="30.7"/>
                    <measurement group_id="O2" value="27.7" lower_limit="15.6" upper_limit="42.6"/>
                    <measurement group_id="O3" value="22.2" lower_limit="14.1" upper_limit="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Pregnancy Rate</title>
        <description>Defined as presence of a gestational sac on transvaginal ultrasound</description>
        <time_frame>Week 4 of study</time_frame>
        <population>FAS with ET population</population>
        <group_list>
          <group group_id="O1">
            <title>FE 999913 100 mg BID</title>
            <description>FE 999913 100 mg vaginal tablet BID</description>
          </group>
          <group group_id="O2">
            <title>FE 999913 100 mg TID</title>
            <description>FE 999913 100 mg vaginal tablet TID</description>
          </group>
          <group group_id="O3">
            <title>FE 999913 Total</title>
            <description>Data pooled from BID and TID groups</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Pregnancy Rate</title>
          <description>Defined as presence of a gestational sac on transvaginal ultrasound</description>
          <population>FAS with ET population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.0" lower_limit="5.3" upper_limit="27.9"/>
                    <measurement group_id="O2" value="29.8" lower_limit="17.3" upper_limit="44.9"/>
                    <measurement group_id="O3" value="22.2" lower_limit="14.1" upper_limit="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Blood Progesterone Concentration</title>
        <time_frame>Weeks 2, 4, 5, 8, and end of study</time_frame>
        <population>FAS population</population>
        <group_list>
          <group group_id="O1">
            <title>FE 999913 100 mg BID</title>
            <description>FE 999913 100 mg vaginal tablet BID</description>
          </group>
          <group group_id="O2">
            <title>FE 999913 100 mg TID</title>
            <description>FE 999913 100 mg vaginal tablet TID</description>
          </group>
          <group group_id="O3">
            <title>FE 999913 Total</title>
            <description>Data pooled from BID and TID groups</description>
          </group>
        </group_list>
        <measure>
          <title>Blood Progesterone Concentration</title>
          <population>FAS population</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="48"/>
                <count group_id="O3" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline; n=46, 48, 94</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.626" spread="0.379"/>
                    <measurement group_id="O2" value="0.704" spread="0.364"/>
                    <measurement group_id="O3" value="0.666" spread="0.371"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2; n=32, 42,74</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" spread="12.0"/>
                    <measurement group_id="O2" value="30.7" spread="37.9"/>
                    <measurement group_id="O3" value="22.3" spread="31.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4; n=6, 14, 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.5" spread="23.1"/>
                    <measurement group_id="O2" value="77.9" spread="41.3"/>
                    <measurement group_id="O3" value="64.2" spread="42.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5; n=6, 14,20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.3" spread="17.0"/>
                    <measurement group_id="O2" value="67.7" spread="35.7"/>
                    <measurement group_id="O3" value="57.1" spread="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8; n=5, 12, 17</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.4" spread="15.7"/>
                    <measurement group_id="O2" value="53.3" spread="23.5"/>
                    <measurement group_id="O3" value="49.8" spread="21.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of study; n=38, 46, 84</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8" spread="16.3"/>
                    <measurement group_id="O2" value="21.9" spread="26.4"/>
                    <measurement group_id="O3" value="16.9" spread="23.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>FE 999913 100 mg BID</title>
          <description>FE 999913 100 mg vaginal tablet BID</description>
        </group>
        <group group_id="E2">
          <title>FE 999913 100 mg TID</title>
          <description>FE 999913 100 mg vaginal tablet TID</description>
        </group>
        <group group_id="E3">
          <title>FE 999913 Total</title>
          <description>Data pooled from BID and TID groups</description>
        </group>
      </group_list>
      <serious_events>
        <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="54"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Subchorionic haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="37" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian hyperstimulation syndrome</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="54"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="54"/>
                <counts group_id="E3" events="22" subjects_affected="22" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Genital haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Cervical polyp</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Heat rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </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 only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Development Support</name_or_title>
      <organization>Ferring Pharmaceuticals</organization>
      <email>DK0-Disclosure@ferring.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/NCT01710514
org study id: 000072
nct id: NCT01710514
lead sponsor: 
has dmc: No
The purposes of the study are to verify sufficient supplementation of luteal hormone after
      administrating FE999913 Vaginal Tablet twice a day (BID) or three times a day (TID) and to
      determine the efficacy and safety of FE999913 Vaginal Tablet in Japanese women undergoing
      fertility treatment with IVF-ET (a fresh embryo transfer).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Proportion of Subjects With Blood Progesterone Concentration Not Less Than 10 ng/ml
time frame: Day 5 of treatment
measure: Ongoing Pregnancy Rate
time frame: Week 5 of study
description: Defined as identification of fetal survival and fetal heart movements on transvaginal ultrasound
measure: Rate of Positive βeta Human Chorionic Gonadotrophin (βhCG)
time frame: Week 2 of study
measure: Clinical Pregnancy Rate
time frame: Week 4 of study
description: Defined as presence of a gestational sac on transvaginal ultrasound
measure: Blood Progesterone Concentration
time frame: Weeks 2, 4, 5, 8, and end of study
arm group label: FE 999913 100 mg BID
arm group type: Active Comparator
description: FE 999913 100 mg vaginal tablet BID
arm group label: FE 999913 100 mg TID
arm group type: Active Comparator
description: FE 999913 100 mg vaginal tablet TID
intervention type: Drug
intervention name: FE 999913 vaginal tablet
arm group label: FE 999913 100 mg BID
arm group label: FE 999913 100 mg TID
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 42 Years
healthy volunteers: No
last name: Clinical Development Support
role: Study Director
affiliation: Ferring Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 