<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/NCT03751124</url>
  </required_header>
  <id_info>
    <org_study_id>MVT-601-035</org_study_id>
    <secondary_id>2018-001368-43</secondary_id>
    <nct_id>NCT03751124</nct_id>
  </id_info>
  <brief_title>Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids</brief_title>
  <official_title>An International Phase 3 Double-Blind, Placebo-Controlled, Randomized Withdrawal Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Myovant Sciences GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Myovant Sciences GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this randomized withdrawal study are to evaluate the long-term efficacy and&#xD;
      safety of the combination of relugolix, estradiol (E2) and norethindrone acetate (NETA), once&#xD;
      daily, for up to 104 weeks in patients with uterine fibroids who have completed a total of 52&#xD;
      weeks of treatment, including a 24-week treatment period in a parent study (study&#xD;
      MVT-601-3001 or MVT-601-3002) and a 28-week treatment period in the open-label extension&#xD;
      study (MVT-601-3003), and who meet the definition of responder, defined as a patient who&#xD;
      demonstrates a menstrual blood loss of &lt; 80 mL and at least a 50% reduction from parent study&#xD;
      baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine&#xD;
      products returned at Week 48 in the extension study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized withdrawal study is an international phase 3 double-blind, placebo-controlled&#xD;
      study that will enroll eligible patients with uterine fibroids who have completed the 24-week&#xD;
      treatment period in a parent study (MVT-601-3001 or MVT-601-3002) and the 28-week treatment&#xD;
      period of the open-label extension study (MVT-601-3003). When including treatment during the&#xD;
      parent study and the extension study, patients completing this randomized withdrawal study&#xD;
      will have received up to a total of 104 weeks of treatment with relugolix.&#xD;
&#xD;
      Approximately 360 women with heavy menstrual bleeding associated with uterine fibroids&#xD;
      completing the extension study with a response to treatment will be eligible to participate&#xD;
      in this study. A responder is defined as a patient who demonstrates a menstrual blood loss of&#xD;
      &lt; 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume&#xD;
      on the alkaline hematin analysis of the feminine products returned at Week 48 in the&#xD;
      extension study.&#xD;
&#xD;
      Screening procedures will be done on the same day as the Week 52 visit for the extension&#xD;
      study. This visit will be referred to as the &quot;Week 52/Baseline visit.&quot; When the Week&#xD;
      52/Baseline procedures in the extension study have been completed, the investigator will&#xD;
      assess patient eligibility for participation in this study. The eligibility assessment will&#xD;
      be based on data available at the Week 52/Baseline visit.&#xD;
&#xD;
      Patients will be asked to provide feminine products for alkaline hematin analysis at each&#xD;
      visit until the analysis confirms the return of heavy menstrual bleeding. The patients will&#xD;
      then be offered retreatment with open-label relugolix with E2/NETA with the onset of the next&#xD;
      menses. They will resume collection of feminine products for alkaline hematin analysis until&#xD;
      two consecutive analyses confirm resolution of heavy menstrual bleeding (menstrual blood loss&#xD;
      of &lt; 80 mL). Safety will be assessed throughout the study by monitoring adverse events, vital&#xD;
      signs, physical examinations, clinical laboratory tests, and assessments of bone mineral&#xD;
      density.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2018</start_date>
  <completion_date type="Actual">November 18, 2021</completion_date>
  <primary_completion_date type="Actual">February 19, 2021</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>
    <intervention_model_description>Randomized withdrawal following an open-label extension to a randomized controlled parent study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of women who maintain a menstrual blood loss (MBL) volume of &lt; 80 mL</measure>
    <time_frame>at Week 24 (Week 72 relative to the parent study baseline)</time_frame>
    <description>MBL volume is measured using the alkaline hematin method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of women who maintain a MBL volume of &lt; 80 mL</measure>
    <time_frame>at Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>MBL volume is measured using the alkaline hematin method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in MBL volume</measure>
    <time_frame>from Baseline up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>MBL volume is measured using the alkaline hematin method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women who responded (MBL volume &lt; 80 mL) to retreatment during retreatment period</measure>
    <time_frame>at Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>MBL volume is measured using the alkaline hematin method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women with heavy menstrual bleeding</measure>
    <time_frame>at Week 24 and 52 (Week 72 and Week 104 relative to the parent study baseline)</time_frame>
    <description>Defined as the proportion of women with MBL volume of ≥ 80 mL at any time. MBL volume is measured using the alkaline hematin method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to resumption of heavy menstrual bleeding</measure>
    <time_frame>up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>Defined as time to MBL volume of ≥ 80 mL. MBL volume is measured using the alkaline hematin method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women with suppression of bleeding</measure>
    <time_frame>at Week 24 and 52 (Week 72 and Week 104 relative to the parent study baseline)</time_frame>
    <description>Will be assessed using patient daily diary and MBL volume measured using the alkaline hematin method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to resumption of menses in women who are amenorrhoeic</measure>
    <time_frame>up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>Will be assessed using patient daily diary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hemoglobin concentration</measure>
    <time_frame>from Baseline up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>Blood samples will be collected from participants for hemoglobin measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in impact on quality of life: UFS-QOL</measure>
    <time_frame>from Baseline up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>Assessed using the Uterine Fibroid Symptom Health-Related Quality of Life Questionnaire (UFS-QOL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient Global Assessment (PGA) for symptoms</measure>
    <time_frame>from Baseline up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>The PGA for symptoms is a 1-item questionnaire designed to assess participants impression of the severity of their symptoms related to uterine fibroids.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PGA for function</measure>
    <time_frame>from Baseline up to Week 52 (Week 104 relative to the parent study baseline)</time_frame>
    <description>The PGA for function is a 1-item questionnaire designed to assess participants impression of how their symptoms related to uterine fibroids affected their usual activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Mineral Density (BMD)</measure>
    <time_frame>from parent study Baseline up to Week 104</time_frame>
    <description>Assessed by dual-energy X-ray absorptiometry (DXA) scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with adverse events (AEs) as a measure of safety and tolerability</measure>
    <time_frame>up to 52 weeks</time_frame>
    <description>Assessed by percentage of participants with AEs and serious AEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum estradiol concentrations</measure>
    <time_frame>up to 52 weeks</time_frame>
    <description>Blood samples will be collected from participants for estradiol measurements.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">229</enrollment>
  <condition>Uterine Leiomyoma</condition>
  <condition>Uterine Fibroids</condition>
  <arm_group>
    <arm_group_label>Relugolix plus E2/NETA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo tablets and capsules</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for relugolix co-administered with placebo for E2/NETA for up to 52 weeks or until heavy menstrual bleeding returns.&#xD;
Retreatment with open-label relugolix with E2/NETA will be offered if heavy menstrual bleeding returns.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Relugolix</intervention_name>
    <description>Relugolix 40 mg tablet administered orally once daily</description>
    <arm_group_label>Relugolix plus E2/NETA</arm_group_label>
    <other_name>TAK-385</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol/norethindrone acetate</intervention_name>
    <description>Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily</description>
    <arm_group_label>Relugolix plus E2/NETA</arm_group_label>
    <other_name>E2/NETA</other_name>
    <other_name>Low-dose hormonal add-back</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for relugolix</intervention_name>
    <description>Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor</description>
    <arm_group_label>Placebo tablets and capsules</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for E2/NETA</intervention_name>
    <description>Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor</description>
    <arm_group_label>Placebo tablets and capsules</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Completed the open-label extension study (MVT-601-3003).&#xD;
&#xD;
          2. Is a responder: Has a menstrual blood loss of &lt; 80 mL AND at least a 50% reduction&#xD;
             from the parent study Baseline based on the results of the alkaline hematin testing&#xD;
             performed on the feminine products returned at the Week 48 visit of the extension&#xD;
             study.&#xD;
&#xD;
          3. Is not expected to undergo gynecological surgery or ablation procedures for uterine&#xD;
             fibroids within the study period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has undergone myomectomy, ultrasound-guided laparoscopic radiofrequency ablation, or&#xD;
             any other surgical procedure for fibroids, uterine artery embolization, magnetic&#xD;
             resonance guided focused ultrasound for fibroids, or endometrial ablation for abnormal&#xD;
             uterine bleeding at any time during the Parent study or extension study.&#xD;
&#xD;
          2. Has a weight that exceeds the weight limit of the DXA scanner&#xD;
&#xD;
          3. Has developed any contraindication to treatment with estradiol or norethindrone&#xD;
             acetate&#xD;
&#xD;
          4. Is currently pregnant or lactating, or intends to become pregnant during the study&#xD;
             period&#xD;
&#xD;
          5. Met a withdrawal criterion in the OLE study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>51 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mesa</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tucson</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canoga Park</name>
      <address>
        <city>Canoga Park</city>
        <state>California</state>
        <zip>91303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntington Beach</name>
      <address>
        <city>Huntington Beach</city>
        <state>California</state>
        <zip>92647</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>La Mesa</name>
      <address>
        <city>La Mesa</city>
        <state>California</state>
        <zip>91942</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norwalk</name>
      <address>
        <city>Norwalk</city>
        <state>California</state>
        <zip>90650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Denver</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakewood</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aventura</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clearwater</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33759</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deland</name>
      <address>
        <city>DeLand</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ft. Lauderdale</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Myers</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jupiter</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Margate</name>
      <address>
        <city>Margate</city>
        <state>Florida</state>
        <zip>33063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>33759</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oviedo</name>
      <address>
        <city>Oviedo</city>
        <state>Florida</state>
        <zip>32765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarasota</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampa</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>United States, Florida</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Palm Beach</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weston</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33327</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>College Park</name>
      <address>
        <city>College Park</city>
        <state>Georgia</state>
        <zip>30349</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dacatur</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duluth</name>
      <address>
        <city>Duluth</city>
        <state>Georgia</state>
        <zip>30097</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norcross</name>
      <address>
        <city>Norcross</city>
        <state>Georgia</state>
        <zip>30093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Savannah</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smyrna</name>
      <address>
        <city>Smyrna</city>
        <state>Georgia</state>
        <zip>30080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oak brook</name>
      <address>
        <city>Oak Brook</city>
        <state>Illinois</state>
        <zip>60523</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shawnee</name>
      <address>
        <city>Shawnee Mission</city>
        <state>Kansas</state>
        <zip>66218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Covington</name>
      <address>
        <city>Covington</city>
        <state>Louisiana</state>
        <zip>70433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marrero</name>
      <address>
        <city>Marrero</city>
        <state>Louisiana</state>
        <zip>70072</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metairie</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Towson</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canton</name>
      <address>
        <city>Canton</city>
        <state>Michigan</state>
        <zip>48187</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Detroit</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Las Vegas</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Las Vegas</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrenceville</name>
      <address>
        <city>Lawrenceville</city>
        <state>New Jersey</state>
        <zip>08648</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Williamsville</name>
      <address>
        <city>Williamsville</city>
        <state>New York</state>
        <zip>14221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Durham</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raleigh</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raleigh</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winston Salem</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bluffton</name>
      <address>
        <city>Bluffton</city>
        <state>South Carolina</state>
        <zip>29910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charleston</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chattanooga</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Longview</name>
      <address>
        <city>Longview</city>
        <state>Texas</state>
        <zip>75605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Webster</name>
      <address>
        <city>Webster</city>
        <state>Texas</state>
        <zip>77598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norfolk</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richmond</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spokane</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>RIO Grande DO SUL</state>
        <zip>90510-040</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>São Bernardo do Campo</name>
      <address>
        <city>São Bernardo Do Campo</city>
        <state>SAO Paulo</state>
        <zip>09715-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sao Paulo</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <zip>01317-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90510-040</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>São Paulo</name>
      <address>
        <city>São Paulo</city>
        <zip>04266-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providencia</name>
      <address>
        <city>Providencia</city>
        <zip>7510186</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Ramon</name>
      <address>
        <city>San Ramón</city>
        <zip>8880465</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santiago</name>
      <address>
        <city>Santiago</city>
        <zip>8360160</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Olomouc</name>
      <address>
        <city>Olomouc</city>
        <zip>772 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pisek</name>
      <address>
        <city>Písek</city>
        <zip>39701</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>České Budějovice</name>
      <address>
        <city>České Budějovice</city>
        <zip>370 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kecskemét</name>
      <address>
        <city>Kecskemét</city>
        <state>Bacs-kiskun</state>
        <zip>6000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debrecen</name>
      <address>
        <city>Debrecen</city>
        <zip>4024</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debrecen</name>
      <address>
        <city>Debrecen</city>
        <zip>4025</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gyula</name>
      <address>
        <city>Gyula</city>
        <zip>5700</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nyíregyháza</name>
      <address>
        <city>Nyíregyháza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szentes</name>
      <address>
        <city>Szentes</city>
        <zip>6600</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catanzaro</name>
      <address>
        <city>Catanzaro</city>
        <zip>88100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roma</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SIENA</name>
      <address>
        <city>Siena</city>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torino</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szczecin</name>
      <address>
        <city>Szczecin</city>
        <state>Zachodniopomorskie</state>
        <zip>71-270</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bialystok</name>
      <address>
        <city>Białystok</city>
        <zip>15-464</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Katowice</name>
      <address>
        <city>Katowice</city>
        <zip>40-123</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poznan</name>
      <address>
        <city>Poznan</city>
        <zip>60-192</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Warszawa</name>
      <address>
        <city>Warszawa</city>
        <zip>02-201</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bloemfontein</name>
      <address>
        <city>Bloemfontein</city>
        <state>Free State</state>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centurion</name>
      <address>
        <city>Centurion</city>
        <state>Gauteng</state>
        <zip>0157</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cape Town</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7405</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cape Town</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7500</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Durban</name>
      <address>
        <city>Durban</city>
        <zip>4126</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roodepoort</name>
      <address>
        <city>Roodepoort</city>
        <zip>1724</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Chile</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>South Africa</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>April 22, 2022</last_update_submitted>
  <last_update_submitted_qc>April 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heavy menstrual bleeding</keyword>
  <keyword>Menorrhagia</keyword>
  <keyword>Uterine Fibroids</keyword>
  <keyword>Uterine Leiomyoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leiomyoma</mesh_term>
    <mesh_term>Myofibroma</mesh_term>
    <mesh_term>Menorrhagia</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Norethindrone</mesh_term>
    <mesh_term>Norethindrone Acetate</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Relugolix</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 26, 2022</submitted>
    <returned>September 23, 2022</returned>
    <submitted>April 24, 2023</submitted>
    <returned>May 18, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03751124
org study id: MVT-601-035
secondary id: 2018-001368-43
nct id: NCT03751124
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objectives of this randomized withdrawal study are to evaluate the long-term efficacy and
      safety of the combination of relugolix, estradiol (E2) and norethindrone acetate (NETA), once
      daily, for up to 104 weeks in patients with uterine fibroids who have completed a total of 52
      weeks of treatment, including a 24-week treatment period in a parent study (study
      MVT-601-3001 or MVT-601-3002) and a 28-week treatment period in the open-label extension
      study (MVT-601-3003), and who meet the definition of responder, defined as a patient who
      demonstrates a menstrual blood loss of < 80 mL and at least a 50% reduction from parent study
      baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine
      products returned at Week 48 in the extension study.
This randomized withdrawal study is an international phase 3 double-blind, placebo-controlled
      study that will enroll eligible patients with uterine fibroids who have completed the 24-week
      treatment period in a parent study (MVT-601-3001 or MVT-601-3002) and the 28-week treatment
      period of the open-label extension study (MVT-601-3003). When including treatment during the
      parent study and the extension study, patients completing this randomized withdrawal study
      will have received up to a total of 104 weeks of treatment with relugolix.

      Approximately 360 women with heavy menstrual bleeding associated with uterine fibroids
      completing the extension study with a response to treatment will be eligible to participate
      in this study. A responder is defined as a patient who demonstrates a menstrual blood loss of
      < 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume
      on the alkaline hematin analysis of the feminine products returned at Week 48 in the
      extension study.

      Screening procedures will be done on the same day as the Week 52 visit for the extension
      study. This visit will be referred to as the "Week 52/Baseline visit." When the Week
      52/Baseline procedures in the extension study have been completed, the investigator will
      assess patient eligibility for participation in this study. The eligibility assessment will
      be based on data available at the Week 52/Baseline visit.

      Patients will be asked to provide feminine products for alkaline hematin analysis at each
      visit until the analysis confirms the return of heavy menstrual bleeding. The patients will
      then be offered retreatment with open-label relugolix with E2/NETA with the onset of the next
      menses. They will resume collection of feminine products for alkaline hematin analysis until
      two consecutive analyses confirm resolution of heavy menstrual bleeding (menstrual blood loss
      of < 80 mL). Safety will be assessed throughout the study by monitoring adverse events, vital
      signs, physical examinations, clinical laboratory tests, and assessments of bone mineral
      density.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized withdrawal following an open-label extension to a randomized controlled parent study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of women who maintain a menstrual blood loss (MBL) volume of < 80 mL
time frame: at Week 24 (Week 72 relative to the parent study baseline)
description: MBL volume is measured using the alkaline hematin method.
measure: Proportion of women who maintain a MBL volume of < 80 mL
time frame: at Week 52 (Week 104 relative to the parent study baseline)
description: MBL volume is measured using the alkaline hematin method.
measure: Change in MBL volume
time frame: from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
description: MBL volume is measured using the alkaline hematin method.
measure: Proportion of women who responded (MBL volume < 80 mL) to retreatment during retreatment period
time frame: at Week 52 (Week 104 relative to the parent study baseline)
description: MBL volume is measured using the alkaline hematin method.
measure: Proportion of women with heavy menstrual bleeding
time frame: at Week 24 and 52 (Week 72 and Week 104 relative to the parent study baseline)
description: Defined as the proportion of women with MBL volume of ≥ 80 mL at any time. MBL volume is measured using the alkaline hematin method.
measure: Time to resumption of heavy menstrual bleeding
time frame: up to Week 52 (Week 104 relative to the parent study baseline)
description: Defined as time to MBL volume of ≥ 80 mL. MBL volume is measured using the alkaline hematin method.
measure: Proportion of women with suppression of bleeding
time frame: at Week 24 and 52 (Week 72 and Week 104 relative to the parent study baseline)
description: Will be assessed using patient daily diary and MBL volume measured using the alkaline hematin method.
measure: Time to resumption of menses in women who are amenorrhoeic
time frame: up to Week 52 (Week 104 relative to the parent study baseline)
description: Will be assessed using patient daily diary.
measure: Change in hemoglobin concentration
time frame: from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
description: Blood samples will be collected from participants for hemoglobin measurements.
measure: Change in impact on quality of life: UFS-QOL
time frame: from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
description: Assessed using the Uterine Fibroid Symptom Health-Related Quality of Life Questionnaire (UFS-QOL)
measure: Change in Patient Global Assessment (PGA) for symptoms
time frame: from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
description: The PGA for symptoms is a 1-item questionnaire designed to assess participants impression of the severity of their symptoms related to uterine fibroids.
measure: Change in PGA for function
time frame: from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
description: The PGA for function is a 1-item questionnaire designed to assess participants impression of how their symptoms related to uterine fibroids affected their usual activities.
measure: Bone Mineral Density (BMD)
time frame: from parent study Baseline up to Week 104
description: Assessed by dual-energy X-ray absorptiometry (DXA) scan.
measure: Percentage of participants with adverse events (AEs) as a measure of safety and tolerability
time frame: up to 52 weeks
description: Assessed by percentage of participants with AEs and serious AEs.
measure: Serum estradiol concentrations
time frame: up to 52 weeks
description: Blood samples will be collected from participants for estradiol measurements.
arm group label: Relugolix plus E2/NETA
arm group type: Experimental
description: Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 52 weeks.
arm group label: Placebo tablets and capsules
arm group type: Placebo Comparator
description: Placebo for relugolix co-administered with placebo for E2/NETA for up to 52 weeks or until heavy menstrual bleeding returns.
Retreatment with open-label relugolix with E2/NETA will be offered if heavy menstrual bleeding returns.
intervention type: Drug
intervention name: Relugolix
description: Relugolix 40 mg tablet administered orally once daily
arm group label: Relugolix plus E2/NETA
other name: TAK-385
intervention type: Drug
intervention name: Estradiol/norethindrone acetate
description: Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily
arm group label: Relugolix plus E2/NETA
other name: E2/NETA
other name: Low-dose hormonal add-back
intervention type: Drug
intervention name: Placebo for relugolix
description: Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor
arm group label: Placebo tablets and capsules
intervention type: Drug
intervention name: Placebo for E2/NETA
description: Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor
arm group label: Placebo tablets and capsules
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 51 Years
healthy volunteers: No
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country: Brazil
country: Chile
country: Czechia
country: Hungary
country: Italy
country: Poland
country: South Africa
country: United States
responsible party type: Sponsor
mesh term: Leiomyoma
mesh term: Myofibroma
mesh term: Menorrhagia
mesh term: Hemorrhage
mesh term: Norethindrone
mesh term: Norethindrone Acetate
mesh term: Estradiol
mesh term: Relugolix
sharing ipd: No
submitted: August 26, 2022
returned: September 23, 2022
submitted: April 24, 2023
returned: May 18, 2023