<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/NCT03291067</url>
  </required_header>
  <id_info>
    <org_study_id>MT-8554-A01</org_study_id>
    <nct_id>NCT03291067</nct_id>
  </id_info>
  <brief_title>MT-8554 for Reduction of Vasomotor Symptoms in Postmenopausal Women</brief_title>
  <official_title>A Randomized, Double Blind, Placebo Controlled Study to Assess the Effect of MT-8554 on the Frequency and Severity of Vasomotor Symptoms in Postmenopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mitsubishi Tanabe Pharma America Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mitsubishi Tanabe Pharma America Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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 purpose of this study is to assess the efficacy and safety of MT-8554 for treatment of&#xD;
      vasomotor symptoms (VMS) associated with menopause.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II randomized, double-blind, placebo-controlled study for dose selection in&#xD;
      postmenopausal women with moderate to severe VMS, defined as follows:&#xD;
&#xD;
        -  Moderate: sensation of heat with sweating, able to continue activity&#xD;
&#xD;
        -  Severe: sensation of heat with sweating, causing cessation of activity This study is&#xD;
           comprised of a screening period, a run-in period and a 12-week double-blind treatment&#xD;
           period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 9, 2017</start_date>
  <completion_date type="Actual">November 9, 2018</completion_date>
  <primary_completion_date type="Actual">October 19, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in the Average Daily Frequency of Moderate to Severe VMS at Weeks 4 and 12</measure>
    <time_frame>Baseline, Weeks 4 and 12</time_frame>
    <description>The average daily frequency of moderate to severe VMS at a time point (Baseline, Weeks 4 and 12) was the average of the frequency of moderate to severe VMS of available diary days in a 7-day window. Changes in the average daily frequency of moderate to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in the Average Daily Severity Score of Mild to Severe VMS at Weeks 4 and 12</measure>
    <time_frame>Baseline, Weeks 4 and 12</time_frame>
    <description>The daily severity score of VMS was defined as (2xFmo + 3xFse)/(Fmo + Fse) for baseline, and (1xFmi + 2xFmo + 3xFse)/(Fmi + Fmo + Fse) for Weeks 4 and 12, where Fmi, Fmo, and Fse were the daily frequencies of mild, moderate, and severe VMS, respectively. The average daily severity score of mild to severe VMS at a time point (Baseline, Week 4 and Week 12) was the average of the daily severity of available diary days in the corresponding 7-day window. The severity score of VMS ranged from 0 (lowest severity) to 3 (highest severity). Change in the average daily severity score of mild to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Responders at Weeks 4 and 12</measure>
    <time_frame>Week 4 and Week 12</time_frame>
    <description>Subjects with cutoff number or greater reduction in the average daily frequency of moderate and severe VMS compared to baseline. The cutoff number was calculated using anchor-based method. The cutoff number was defined as numerical value to maximize the sensitivity and the specificity, using Patient Global Impression of Change (PGIC) as the anchor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Insomnia Severity Index at Week 4 and Week 12</measure>
    <time_frame>Baseline, Weeks 4 and 12</time_frame>
    <description>The Insomnia Severity Index was a self-rated, 7-item validated sleep scale that measured clinical insomnia severity. The total score ranged from 0-28 where higher values indicated increased severity of insomnia.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">375</enrollment>
  <condition>Menopause Hot Flashes</condition>
  <arm_group>
    <arm_group_label>MT-8554 1mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>MT-8554 5mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>MT-8554 10mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-8554 1mg</intervention_name>
    <description>MT-8554 1mg QD, oral, 12 weeks</description>
    <arm_group_label>MT-8554 1mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-8554 5mg</intervention_name>
    <description>MT-8554 5mg QD, oral, 12 weeks</description>
    <arm_group_label>MT-8554 5mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-8554 10mg</intervention_name>
    <description>MT-8554 10mg QD, oral, 12 weeks</description>
    <arm_group_label>MT-8554 10mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo QD, oral, 12 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Additional screening criteria check may apply for qualification:&#xD;
&#xD;
          -  Provide written informed consent to participate in this study&#xD;
&#xD;
          -  Spontaneous amenorrhea for ≥12 months; or spontaneous amenorrhea for at least 6 months&#xD;
             and with follicle stimulating hormone (FSH) levels &gt;40 mIU/mL; or documented bilateral&#xD;
             salpingo oophorectomy ≥6 weeks, with or without hysterectomy&#xD;
&#xD;
          -  7 or more moderate to severe VMS per day, or 50 or more moderate to severe VMS per&#xD;
             week&#xD;
&#xD;
          -  Have a consistent bedtime on at least 5 nights per week&#xD;
&#xD;
          -  Mean VMS frequency during the Placebo Run in period does not drop by more than 50%&#xD;
             from the mean level reported for 2 weeks during the Screening period&#xD;
&#xD;
          -  VMS diary compliance &gt;50%&#xD;
&#xD;
          -  In the Investigator's opinion, subject is able to understand the nature of the study&#xD;
             and any risk involved in participation, and is willing to cooperate and comply with&#xD;
             the protocol restrictions and requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Additional screening criteria check may apply for qualification:&#xD;
&#xD;
          -  History of any cancer within 5 years except for basal cell carcinoma&#xD;
&#xD;
          -  History of undiagnosed abnormal vaginal bleeding&#xD;
&#xD;
          -  History of Hepatitis B, Hepatitis C or HIV&#xD;
&#xD;
          -  History of psychiatric illness, excessive alcohol intake or use of recreational drugs&#xD;
             who are unsuitable for study enrollment and compliance&#xD;
&#xD;
          -  Presence or history of severe adverse reaction or allergy to any drug&#xD;
&#xD;
          -  Peripheral vascular disease or disorders with associated vasculopathies&#xD;
&#xD;
          -  Clinically significant conditions which could interfere with the objectives of the&#xD;
             study or the safety of the subject, as judged by the Investigator&#xD;
&#xD;
          -  Endometrial thickness of &gt;=5 mm as measured by transvaginal ultrasound&#xD;
&#xD;
          -  Abnormal result from baseline endometrial biopsy (i.e., endometrial hyperplasia or&#xD;
             endometrial cancer)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin&#xD;
             ≥2.0 × upper limit of normal (ULN) above the reference range&#xD;
&#xD;
          -  Subjects of childbearing potential&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Head of Medical Science</last_name>
    <role>Study Director</role>
    <affiliation>Mitsubishi Tanabe Pharma America Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dothan</city>
        <state>Alabama</state>
        <zip>36303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Norwalk</city>
        <state>California</state>
        <zip>90650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New London</city>
        <state>Connecticut</state>
        <zip>06320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New London</city>
        <state>Connecticut</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33759</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Crystal River</city>
        <state>Florida</state>
        <zip>34429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33185</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33186</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ponte Vedra</city>
        <state>Florida</state>
        <zip>32081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Port Saint Lucie</city>
        <state>Florida</state>
        <zip>34952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wellington</city>
        <state>Florida</state>
        <zip>33414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sandy Springs</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Idaho Falls</city>
        <state>Idaho</state>
        <zip>83404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ankeny</city>
        <state>Iowa</state>
        <zip>50023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Marrero</city>
        <state>Louisiana</state>
        <zip>70072</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Missoula</city>
        <state>Montana</state>
        <zip>59808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lawrenceville</city>
        <state>New Jersey</state>
        <zip>08648</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Morehead City</city>
        <state>North Carolina</state>
        <zip>28557</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Englewood</city>
        <state>Ohio</state>
        <zip>45322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bristol</city>
        <state>Tennessee</state>
        <zip>37620</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jackson</city>
        <state>Tennessee</state>
        <zip>38305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Schertz</city>
        <state>Texas</state>
        <zip>78154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Draper</city>
        <state>Utah</state>
        <zip>84020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ogden</city>
        <state>Utah</state>
        <zip>84403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Covington</city>
        <state>Washington</state>
        <zip>98042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <results_first_submitted>October 14, 2021</results_first_submitted>
  <results_first_submitted_qc>December 6, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 4, 2022</results_first_posted>
  <disposition_first_submitted>October 16, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>December 6, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 4, 2022</disposition_first_posted>
  <last_update_submitted>May 12, 2023</last_update_submitted>
  <last_update_submitted_qc>May 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hot Flashes</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 22, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03291067/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03291067/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>One subject with dual status of the run-in-failure and randomized in error in MT-8554 5 mg group was excluded from the Randomized Population.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>MT-8554 1mg</title>
          <description>MT-8554 1mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="P2">
          <title>MT-8554 5mg</title>
          <description>MT-8554 5mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="P3">
          <title>MT-8554 10mg</title>
          <description>MT-8554 10mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Placebo QD, oral, 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="94"/>
                <participants group_id="P2" count="92"/>
                <participants group_id="P3" count="94"/>
                <participants group_id="P4" count="94"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="95"/>
                <participants group_id="P2" count="90"/>
                <participants group_id="P3" count="93"/>
                <participants group_id="P4" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="84"/>
                <participants group_id="P2" count="78"/>
                <participants group_id="P3" count="61"/>
                <participants group_id="P4" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="33"/>
                <participants group_id="P4" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="17"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Overall number of baseline participants were number of participants who received at least one study medication which was indicated as &quot;Treated&quot; in the above Participant Flow module. 94 subjects were originally randomized to MT-8554 1mg group; but one subject in the placebo group took one week of MT-8554 1mg treatment in error. For calculation of &quot;Treated&quot; subjects, the subject was counted as MT-8554 1mg group so that &quot;Treated&quot; subjects in MT-8554 1 mg group was 95 subjects.</population>
      <group_list>
        <group group_id="B1">
          <title>MT-8554 1mg</title>
          <description>MT-8554 1mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="B2">
          <title>MT-8554 5mg</title>
          <description>MT-8554 5mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="B3">
          <title>MT-8554 10mg</title>
          <description>MT-8554 10mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Placebo QD, oral, 12 weeks</description>
        </group>
        <group group_id="B5">
          <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="95"/>
            <count group_id="B2" value="90"/>
            <count group_id="B3" value="93"/>
            <count group_id="B4" value="90"/>
            <count group_id="B5" value="368"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.5" spread="6.27"/>
                    <measurement group_id="B2" value="54.6" spread="6.62"/>
                    <measurement group_id="B3" value="56.0" spread="6.55"/>
                    <measurement group_id="B4" value="55.7" spread="6.25"/>
                    <measurement group_id="B5" value="55.2" spread="6.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="93"/>
                    <measurement group_id="B4" value="90"/>
                    <measurement group_id="B5" value="368"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_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="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="28"/>
                    <measurement group_id="B5" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="74"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="74"/>
                    <measurement group_id="B4" value="62"/>
                    <measurement group_id="B5" value="274"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Average Daily Frequency of Moderate to Severe VMS at Weeks 4 and 12</title>
        <description>The average daily frequency of moderate to severe VMS at a time point (Baseline, Weeks 4 and 12) was the average of the frequency of moderate to severe VMS of available diary days in a 7-day window. Changes in the average daily frequency of moderate to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.</description>
        <time_frame>Baseline, Weeks 4 and 12</time_frame>
        <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>MT-8554 1mg</title>
            <description>MT-8554 1mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>MT-8554 5mg</title>
            <description>MT-8554 5mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>MT-8554 10mg</title>
            <description>MT-8554 10mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo QD, oral, 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Average Daily Frequency of Moderate to Severe VMS at Weeks 4 and 12</title>
          <description>The average daily frequency of moderate to severe VMS at a time point (Baseline, Weeks 4 and 12) was the average of the frequency of moderate to severe VMS of available diary days in a 7-day window. Changes in the average daily frequency of moderate to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.</description>
          <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment</population>
          <units>VMS per day</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="89"/>
                <count group_id="O4" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.92" spread="0.609"/>
                    <measurement group_id="O2" value="-2.75" spread="0.705"/>
                    <measurement group_id="O3" value="-2.75" spread="0.734"/>
                    <measurement group_id="O4" value="-1.39" spread="0.705"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.91" spread="0.690"/>
                    <measurement group_id="O2" value="-3.11" spread="0.780"/>
                    <measurement group_id="O3" value="-3.38" spread="0.821"/>
                    <measurement group_id="O4" value="-2.78" spread="0.779"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Average Daily Severity Score of Mild to Severe VMS at Weeks 4 and 12</title>
        <description>The daily severity score of VMS was defined as (2xFmo + 3xFse)/(Fmo + Fse) for baseline, and (1xFmi + 2xFmo + 3xFse)/(Fmi + Fmo + Fse) for Weeks 4 and 12, where Fmi, Fmo, and Fse were the daily frequencies of mild, moderate, and severe VMS, respectively. The average daily severity score of mild to severe VMS at a time point (Baseline, Week 4 and Week 12) was the average of the daily severity of available diary days in the corresponding 7-day window. The severity score of VMS ranged from 0 (lowest severity) to 3 (highest severity). Change in the average daily severity score of mild to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.</description>
        <time_frame>Baseline, Weeks 4 and 12</time_frame>
        <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>MT-8554 1mg</title>
            <description>MT-8554 1mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>MT-8554 5mg</title>
            <description>MT-8554 5mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>MT-8554 10mg</title>
            <description>MT-8554 10mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo QD, oral, 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Average Daily Severity Score of Mild to Severe VMS at Weeks 4 and 12</title>
          <description>The daily severity score of VMS was defined as (2xFmo + 3xFse)/(Fmo + Fse) for baseline, and (1xFmi + 2xFmo + 3xFse)/(Fmi + Fmo + Fse) for Weeks 4 and 12, where Fmi, Fmo, and Fse were the daily frequencies of mild, moderate, and severe VMS, respectively. The average daily severity score of mild to severe VMS at a time point (Baseline, Week 4 and Week 12) was the average of the daily severity of available diary days in the corresponding 7-day window. The severity score of VMS ranged from 0 (lowest severity) to 3 (highest severity). Change in the average daily severity score of mild to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.</description>
          <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment</population>
          <units>VMS severity score per day</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="89"/>
                <count group_id="O4" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.302" spread="0.0609"/>
                    <measurement group_id="O2" value="-0.407" spread="0.0714"/>
                    <measurement group_id="O3" value="-0.305" spread="0.0740"/>
                    <measurement group_id="O4" value="-0.316" spread="0.0712"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.374" spread="0.0725"/>
                    <measurement group_id="O2" value="-0.481" spread="0.0822"/>
                    <measurement group_id="O3" value="-0.433" spread="0.0864"/>
                    <measurement group_id="O4" value="-0.388" spread="0.0819"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Responders at Weeks 4 and 12</title>
        <description>Subjects with cutoff number or greater reduction in the average daily frequency of moderate and severe VMS compared to baseline. The cutoff number was calculated using anchor-based method. The cutoff number was defined as numerical value to maximize the sensitivity and the specificity, using Patient Global Impression of Change (PGIC) as the anchor.</description>
        <time_frame>Week 4 and Week 12</time_frame>
        <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment. The subjects without VMS frequency data at Week 4 were excluded from the analysis at Week 4. The subjects without VMS frequency data at Week 12 were excluded from the analysis at Week 12.</population>
        <group_list>
          <group group_id="O1">
            <title>MT-8554 1mg</title>
            <description>MT-8554 1mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>MT-8554 5mg</title>
            <description>MT-8554 5mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>MT-8554 10mg</title>
            <description>MT-8554 10mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo QD, oral, 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders at Weeks 4 and 12</title>
          <description>Subjects with cutoff number or greater reduction in the average daily frequency of moderate and severe VMS compared to baseline. The cutoff number was calculated using anchor-based method. The cutoff number was defined as numerical value to maximize the sensitivity and the specificity, using Patient Global Impression of Change (PGIC) as the anchor.</description>
          <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment. The subjects without VMS frequency data at Week 4 were excluded from the analysis at Week 4. The subjects without VMS frequency data at Week 12 were excluded from the analysis at Week 12.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="89"/>
                <count group_id="O4" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="88"/>
                    <count group_id="O2" value="82"/>
                    <count group_id="O3" value="72"/>
                    <count group_id="O4" value="86"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.8"/>
                    <measurement group_id="O2" value="52.4"/>
                    <measurement group_id="O3" value="36.1"/>
                    <measurement group_id="O4" value="36.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="76"/>
                    <count group_id="O3" value="61"/>
                    <count group_id="O4" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.4"/>
                    <measurement group_id="O2" value="60.5"/>
                    <measurement group_id="O3" value="54.1"/>
                    <measurement group_id="O4" value="54.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Insomnia Severity Index at Week 4 and Week 12</title>
        <description>The Insomnia Severity Index was a self-rated, 7-item validated sleep scale that measured clinical insomnia severity. The total score ranged from 0-28 where higher values indicated increased severity of insomnia.</description>
        <time_frame>Baseline, Weeks 4 and 12</time_frame>
        <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment</population>
        <group_list>
          <group group_id="O1">
            <title>MT-8554 1mg</title>
            <description>MT-8554 1mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>MT-8554 5mg</title>
            <description>MT-8554 5mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>MT-8554 10mg</title>
            <description>MT-8554 10mg QD, oral, 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo QD, oral, 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Insomnia Severity Index at Week 4 and Week 12</title>
          <description>The Insomnia Severity Index was a self-rated, 7-item validated sleep scale that measured clinical insomnia severity. The total score ranged from 0-28 where higher values indicated increased severity of insomnia.</description>
          <population>Intent-to-treat (ITT) population=All randomized subjects who have at least 1 post-baseline efficacy assessment</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="89"/>
                <count group_id="O4" value="91"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" spread="0.49"/>
                    <measurement group_id="O2" value="-3.1" spread="0.51"/>
                    <measurement group_id="O3" value="-3.6" spread="0.55"/>
                    <measurement group_id="O4" value="-1.8" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.2" spread="0.53"/>
                    <measurement group_id="O2" value="-2.7" spread="0.55"/>
                    <measurement group_id="O3" value="-2.4" spread="0.54"/>
                    <measurement group_id="O4" value="-3.0" spread="0.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Week 12</time_frame>
      <desc>One subject was randomized to placebo group; but the subject got one week of MT-8554 1 mg treatment so that the subject was counted as MT-8554 1 mg group in the Safety Population. Total of 6 subjects (3 on placebo, 2 on MT-8554 5 mg and 1 on MT-8554 10 mg) did not take any study medication so that these subjects were excluded from the Safety Population.</desc>
      <group_list>
        <group group_id="E1">
          <title>MT-8554 1mg</title>
          <description>MT-8554 1mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="E2">
          <title>MT-8554 5mg</title>
          <description>MT-8554 5mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="E3">
          <title>MT-8554 10mg</title>
          <description>MT-8554 10mg QD, oral, 12 weeks</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Placebo QD, oral, 12 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="46" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="37" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia oral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oral discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Paraesthesia oral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Swollen tongue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Feeling hot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Feeling jittery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Feeling of body temperature change</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hypothermia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bronchitis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Chronic sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Viral rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Joint dislocation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Meniscus injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Periorbital haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Biopsy endometrium abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood urine present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Body temperature decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Electrocardiogram ST-T change</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Electrocardiogram T wave amplitude decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Electrocardiogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Low density lipoprotein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Neutrophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oestradiol increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Prothrombin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Red blood cells urine positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>White blood cells urine positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Fibromyalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Neck mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Parosmia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Sinus headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nightmare</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Sleep inertia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Breast tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Rectocele</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine polyp</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Uterine prolapse</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vulvovaginal dryness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pharyngeal hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pharyngeal oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cold sweat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nail disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Skin burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Peripheral coldness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trials, Information Desk</name_or_title>
      <organization>Mitsubishi Tanabe Pharma Development America, Inc.</organization>
      <phone>Please e-mail</phone>
      <email>information@mt-pharma-us.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/NCT03291067
org study id: MT-8554-A01
nct id: NCT03291067
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the efficacy and safety of MT-8554 for treatment of
      vasomotor symptoms (VMS) associated with menopause.
This is a Phase II randomized, double-blind, placebo-controlled study for dose selection in
      postmenopausal women with moderate to severe VMS, defined as follows:

        -  Moderate: sensation of heat with sweating, able to continue activity

        -  Severe: sensation of heat with sweating, causing cessation of activity This study is
           comprised of a screening period, a run-in period and a 12-week double-blind treatment
           period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change From Baseline in the Average Daily Frequency of Moderate to Severe VMS at Weeks 4 and 12
time frame: Baseline, Weeks 4 and 12
description: The average daily frequency of moderate to severe VMS at a time point (Baseline, Weeks 4 and 12) was the average of the frequency of moderate to severe VMS of available diary days in a 7-day window. Changes in the average daily frequency of moderate to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.
measure: Change From Baseline in the Average Daily Severity Score of Mild to Severe VMS at Weeks 4 and 12
time frame: Baseline, Weeks 4 and 12
description: The daily severity score of VMS was defined as (2xFmo + 3xFse)/(Fmo + Fse) for baseline, and (1xFmi + 2xFmo + 3xFse)/(Fmi + Fmo + Fse) for Weeks 4 and 12, where Fmi, Fmo, and Fse were the daily frequencies of mild, moderate, and severe VMS, respectively. The average daily severity score of mild to severe VMS at a time point (Baseline, Week 4 and Week 12) was the average of the daily severity of available diary days in the corresponding 7-day window. The severity score of VMS ranged from 0 (lowest severity) to 3 (highest severity). Change in the average daily severity score of mild to severe VMS at Week 4 and Week 12 compared to baseline were evaluated.
measure: Percentage of Responders at Weeks 4 and 12
time frame: Week 4 and Week 12
description: Subjects with cutoff number or greater reduction in the average daily frequency of moderate and severe VMS compared to baseline. The cutoff number was calculated using anchor-based method. The cutoff number was defined as numerical value to maximize the sensitivity and the specificity, using Patient Global Impression of Change (PGIC) as the anchor.
measure: Change From Baseline in the Insomnia Severity Index at Week 4 and Week 12
time frame: Baseline, Weeks 4 and 12
description: The Insomnia Severity Index was a self-rated, 7-item validated sleep scale that measured clinical insomnia severity. The total score ranged from 0-28 where higher values indicated increased severity of insomnia.
arm group label: MT-8554 1mg
arm group type: Experimental
arm group label: MT-8554 5mg
arm group type: Experimental
arm group label: MT-8554 10mg
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: MT-8554 1mg
description: MT-8554 1mg QD, oral, 12 weeks
arm group label: MT-8554 1mg
intervention type: Drug
intervention name: MT-8554 5mg
description: MT-8554 5mg QD, oral, 12 weeks
arm group label: MT-8554 5mg
intervention type: Drug
intervention name: MT-8554 10mg
description: MT-8554 10mg QD, oral, 12 weeks
arm group label: MT-8554 10mg
intervention type: Drug
intervention name: Placebo
description: Placebo QD, oral, 12 weeks
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Head of Medical Science
role: Study Director
affiliation: Mitsubishi Tanabe Pharma America Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hot Flashes
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 