<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/NCT03750552</url>
  </required_header>
  <id_info>
    <org_study_id>0169</org_study_id>
    <secondary_id>2018-003289-15</secondary_id>
    <nct_id>NCT03750552</nct_id>
  </id_info>
  <brief_title>Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure</brief_title>
  <acronym>SEQUOIA</acronym>
  <official_title>A Phase 3, 4-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of TD-9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects With Primary Autonomic Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Theravance Biopharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Theravance Biopharma</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>
      A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in&#xD;
      subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH with up to 4&#xD;
      weeks of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to&#xD;
      evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with&#xD;
      primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH. The study consists of 3&#xD;
      periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up.&#xD;
      The trial utilizes an operational design featuring the ability to conduct protocol required&#xD;
      visits as either in clinic or remote visits (except Screening visit).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 24, 2019</start_date>
  <completion_date type="Actual">July 21, 2021</completion_date>
  <primary_completion_date type="Actual">July 21, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Parallel assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4</measure>
    <time_frame>Baseline and Week 4</time_frame>
    <description>OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4</measure>
    <time_frame>Baseline and Week 4</time_frame>
    <description>OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4</measure>
    <time_frame>Baseline and Week 4</time_frame>
    <description>OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4</measure>
    <time_frame>Baseline and Week 4</time_frame>
    <description>PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced at Least One Fall</measure>
    <time_frame>Up to Week 4</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">195</enrollment>
  <condition>Symptomatic Neurogenic Orthostatic Hypotension</condition>
  <arm_group>
    <arm_group_label>ampreloxetine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ampreloxetine</intervention_name>
    <description>Oral tablet, QD</description>
    <arm_group_label>ampreloxetine</arm_group_label>
    <other_name>TD-9855</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral tablet, QD</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is male or female and at least 30 years old.&#xD;
&#xD;
          -  Subject must meet the diagnostic criteria of symptomatic nOH, as demonstrated by a&#xD;
             sustained reduction in BP of ≥20 mm Hg (systolic) or ≥10 mm Hg (diastolic) within 3&#xD;
             minutes of being tilted-up to ≥60o from a supine position as determined by a&#xD;
             tilt-table test.&#xD;
&#xD;
          -  Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment&#xD;
             Question #1 at randomization visit.&#xD;
&#xD;
          -  For subjects with PD only: Subject has a diagnosis of PD according to the United&#xD;
             Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria (1992).&#xD;
&#xD;
          -  For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the&#xD;
             Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman&#xD;
             Criteria (2008).&#xD;
&#xD;
          -  For subjects with PAF only: Subject has documented impaired autonomic reflexes,&#xD;
             including the Valsalva maneuver performed within 24 months from the date of&#xD;
             randomization.&#xD;
&#xD;
          -  Subject has plasma NE levels &gt;100 pg/mL after being in seated position for 30 minutes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has a known systemic illness known to produce autonomic neuropathy, including&#xD;
             but not limited to amyloidosis, and autoimmune neuropathies.&#xD;
&#xD;
          -  Subject has a known intolerance to other NRIs or SNRIs.&#xD;
&#xD;
          -  Subject currently uses concomitant antihypertensive medication for the treatment of&#xD;
             essential hypertension unrelated to autonomic dysfunction.&#xD;
&#xD;
          -  Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives,&#xD;
             whichever is longer, prior to randomization or requires concomitant use until the&#xD;
             follow-up visit.&#xD;
&#xD;
          -  Subject has changed dose, frequency, or type of prescribed medication for orthostatic&#xD;
             hypotension within 7 days prior to V1.&#xD;
&#xD;
               -  Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior&#xD;
                  to V1.&#xD;
&#xD;
          -  Subject has a known or suspected alcohol or substance abuse within the past 12 months&#xD;
             (DSM-IV-TR® definition of alcohol or substance abuse).&#xD;
&#xD;
          -  Subject has a clinically unstable coronary artery disease, or major cardiovascular or&#xD;
             neurological event in the past 6 months.&#xD;
&#xD;
          -  Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to&#xD;
             randomization.&#xD;
&#xD;
          -  Subject has a history of untreated closed angle glaucoma, or treated closed angle&#xD;
             glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk&#xD;
             to the subject.&#xD;
&#xD;
          -  Subject has any significant uncontrolled cardiac arrhythmia.&#xD;
&#xD;
          -  Subject has a Montreal Cognitive Assessment (MoCA) ≤23.&#xD;
&#xD;
          -  Subject had a myocardial infarction in the past 6 months or has current unstable&#xD;
             angina.&#xD;
&#xD;
          -  Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3&#xD;
             or 4).&#xD;
&#xD;
          -  Subject has a clinically significant abnormal laboratory findings (e.g., alanine&#xD;
             aminotransferase [ALT] or aspartate aminotransferase [AST] &gt;3.0 x upper limit of&#xD;
             normal [ULN]; blood bilirubin [total] &gt;1.5 x ULN; estimated glomerular filtration rate&#xD;
             (eGFR) &lt;30 mL/min/1.73m2, or any abnormal laboratory value that could interfere with&#xD;
             safety of the subject).&#xD;
&#xD;
          -  Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal&#xD;
             behavior, as outlined by the C-SSRS (Columbia Suicide Severity Rating Scale)&#xD;
             (Baseline/Screening Version) subject should be assessed by the rater for risk of&#xD;
             suicide and the subject's appropriateness for inclusion in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor</last_name>
    <role>Study Director</role>
    <affiliation>Theravance Biopharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner Sun Health Research Institute</name>
      <address>
        <city>Sun City</city>
        <state>Arizona</state>
        <zip>85351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network, LLC</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Neuroscience Health Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Springs Neurological Associates, PC</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Health</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80538</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Hospital, Dept. of Neurology</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease and Movement Disorders Center</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SFM Clinical Research</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33487</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fixel Institute for Neurological Diseases</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurostudies, Inc</name>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <zip>33952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University Health System</name>
      <address>
        <city>Glenview</city>
        <state>Illinois</state>
        <zip>60026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers New Jersey Medical School</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Hospital</name>
      <address>
        <city>McLean</city>
        <state>Virginia</state>
        <zip>22101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inland Northwest Research</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Concord Hospital</name>
      <address>
        <city>Concord</city>
        <state>New South Wales</state>
        <zip>2139</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Health - Clinical Trials Centre</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Melbourne Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Perron Institute for Neurological and Translational Science, QEII Medical Centre</name>
      <address>
        <city>Nedlands</city>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universitat Innsbruck Abteilung Fur Neurologie</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tulln</name>
      <address>
        <city>Tulln</city>
        <zip>3430</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wilhelminenspital Wien Abteilung fur Neurologie</name>
      <address>
        <city>Wien</city>
        <zip>1160</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT Sveti Georgi EAD Clinic of Neurological Diseases</name>
      <address>
        <city>Plovdiv</city>
        <zip>4000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHATNP Sv.Naum, EAD</name>
      <address>
        <city>Sofia</city>
        <zip>1113</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT Alexandrovska EAD Clinic of Neurological Diseases</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre-CCIT</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network - Toronto Western Hospital Movement Disorders Clinic</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal Neurological Institute and Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3A 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bispebjerg og Frederiksberg Hospital</name>
      <address>
        <city>Copenhagen</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense Universitetshospital</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Tallinn Central Hospital</name>
      <address>
        <city>Tallinn</city>
        <zip>10138</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Astra Team Clinic</name>
      <address>
        <city>Tallinn</city>
        <zip>11315</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tartu University Hospital</name>
      <address>
        <city>Tartu</city>
        <zip>50406</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Roger Salengro - CHU Lille</name>
      <address>
        <city>Lille Cedex</city>
        <state>Nord</state>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Caremeau</name>
      <address>
        <city>Nîmes</city>
        <zip>30029</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pierre Paul Rquet, CHU Purpan</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Freiburg - Klinik fur Neurologie und Neurophysiologie</name>
      <address>
        <city>Freiburg</city>
        <state>Baden Wuerttemberg</state>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gemeinschaftspraxis Dr. med. J. Springub/ W. Schwarz</name>
      <address>
        <city>Westerstede</city>
        <state>Niedersachsen</state>
        <zip>26655</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Oehlwein</name>
      <address>
        <city>Gera</city>
        <state>Thueringen</state>
        <zip>07551</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Universitatsmedizin Berlin - Campus Benjamin Franklin</name>
      <address>
        <city>Berlin</city>
        <zip>12 203</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexianer St. Joseph-Krankenhaus Berlin-Weißensee, Klinik für Neurologie</name>
      <address>
        <city>Berlin</city>
        <zip>13088</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite - Campus Virchow-Klinikum, Klinik fur Neurologie</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite - Campus Virchow-Klinikum</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinexpert Kft.</name>
      <address>
        <city>Budapest</city>
        <zip>1033</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem</name>
      <address>
        <city>Budapest</city>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pecsi Tudomanyegyetem, Neurologiai Klinika</name>
      <address>
        <city>Pécs</city>
        <zip>7623</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szent Borbala Korhaz</name>
      <address>
        <city>Tatabanya</city>
        <zip>2800</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaplan Medical Center</name>
      <address>
        <city>Rehovot</city>
        <zip>7610001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziv Medical Center</name>
      <address>
        <city>Safed</city>
        <zip>1311001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical Center</name>
      <address>
        <city>Tel HaShomer</city>
        <zip>5262101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas - IRCCS</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Istituto G.Giglio di Cefalù</name>
      <address>
        <city>Cefalù</city>
        <state>Palermo</state>
        <zip>90015</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona Umberto I - G.M. Lancisi - G. Salesi, SOD Clinica di Neuroriabilitazione</name>
      <address>
        <city>Ancona</city>
        <zip>60126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche Ospedale Bellaria</name>
      <address>
        <city>Bologna</city>
        <zip>40139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero - Universitaria Policlinico Vittorio Emanuele. - P.O G. Rodolico, Clinica Neurologica</name>
      <address>
        <city>Catania</city>
        <zip>95123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universita Gabriele D'Annunzio- Cesi-Met</name>
      <address>
        <city>Chieti</city>
        <zip>66100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele I U.O. di Neurologia</name>
      <address>
        <city>Milano</city>
        <zip>58-20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione PTV - Policlinico Tor Vergata I U.O.C. Neurologia</name>
      <address>
        <city>Roma</city>
        <zip>00133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Giovanni Battista del Sovrano Militare Ordine di Malta</name>
      <address>
        <city>Roma</city>
        <zip>00148</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Giovanni Battista</name>
      <address>
        <city>Roma</city>
        <zip>00148</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I - Universita degli Studi di Roma La Sapienza / Neurologia</name>
      <address>
        <city>Roma</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS / Istituto di Neurologia - Ambulatorio Disturbi del Movimento</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sapienza University of Rome</name>
      <address>
        <city>Roma</city>
        <zip>00185</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU San Giovanni di Dio e Ruggi d'Aragona</name>
      <address>
        <city>Salerno</city>
        <zip>84131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Santa Maria</name>
      <address>
        <city>Terni</city>
        <zip>5100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Zealand Brain Research Institute</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specjalistyczna Praktyka Lekarska prof.Grzegorz Opala</name>
      <address>
        <city>Katowice</city>
        <zip>40-588</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PRATIA MCM Kraków</name>
      <address>
        <city>Kraków</city>
        <zip>30-510</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej</name>
      <address>
        <city>Kraków</city>
        <zip>31-505</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie</name>
      <address>
        <city>Lublin</city>
        <zip>20-954</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Zdrowia dr Boczarska-Jedynak</name>
      <address>
        <city>Oświęcim</city>
        <zip>32-600</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEURO-CARE Sp. z o.o. Sp. Komandytowa</name>
      <address>
        <city>Siemianowice Śląskie</city>
        <zip>41-100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ETG Warszawa</name>
      <address>
        <city>Warszawa</city>
        <zip>02-777</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specjalistyczne Gabinety sp. z o.o.</name>
      <address>
        <city>Warszawa</city>
        <zip>30-539</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Senhora da Oliveira - Guimaraes, EPE</name>
      <address>
        <city>Guimaraes</city>
        <zip>4835-044</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar e Universitario Lisboa Norte - Hospital de Santa Maria</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Campus Neurologico Senior</name>
      <address>
        <city>Torres Vedras</city>
        <zip>2560-280</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Autonomous Institution of Healthcare Republican Clinical Hospital of the Ministry of Healthcare of Republic Tatarstan</name>
      <address>
        <city>Kazan</city>
        <state>Tatarstan</state>
        <zip>420064</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Institution Federal Sibirian Scientific and Clinical Center of Federal Medico-Biological Agency</name>
      <address>
        <city>Krasnoyarsk</city>
        <zip>660037</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Additional Professional Education Russian Medical Academy of Continuous Postgraduate Education of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <zip>125284</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHI Central Clinical Hospital #2 of JSC Russian Railways N.A. Semashko</name>
      <address>
        <city>Moscow</city>
        <zip>129128</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Neurological Center Sibneiromed</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630091</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBEIHPE Novosibirsk State Medical University</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630091</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Institution National Medical Research Centre of psychiatry and neurology named after V.M. Bekhterev of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>192019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Human Brain Institute RAMS</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197376</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Petersburg State Budgetary Institution of Healthcare City Hospital # 40 of Kurortnyi Region</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197706</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional State Budgetary Institution of Healthcare Smolensk Regional Clinical Hospital</name>
      <address>
        <city>Smolensk</city>
        <zip>214018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Donostia</name>
      <address>
        <city>San Sebastián</city>
        <state>Guipuzcoa</state>
        <zip>20014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Navarrabiomed Fundacion Miguel Servet</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Cruces</name>
      <address>
        <city>Barakaldo</city>
        <state>Vizcaya</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Mutua de Terrasa</name>
      <address>
        <city>Barcelona</city>
        <zip>08222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta del Mar</name>
      <address>
        <city>Cadiz</city>
        <zip>11009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de La Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Institution Dnipropetrovsk I.I.Mechnikov RCH</name>
      <address>
        <city>Dnipro</city>
        <zip>49005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Noncommercial Enterprise City Policlinic #9 of Kharkiv City Council</name>
      <address>
        <city>Kharkiv</city>
        <zip>61172</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital Dept of Neurology</name>
      <address>
        <city>Lviv</city>
        <zip>79010</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNE Acad O.I. Yushchenko Vinnytsia Reg Psychoneurological Hospital of Vinnytsia Regional Council, Department of Neurology</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Institution City Clinical Hospital #6</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69035</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Devon and Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <state>Devon</state>
        <zip>EX2 5DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Re:Cognition Health</name>
      <address>
        <city>Plymouth</city>
        <state>Devon</state>
        <zip>PL6 8BT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Hospital</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The National Hospital for Neurology &amp; Neurosurgery</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <state>Manchester</state>
        <zip>SES 9PJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Re:Cognition Health Ltd</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B16 8LT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Re:Cognition Health</name>
      <address>
        <city>London</city>
        <zip>W1G 9JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salford Royal</name>
      <address>
        <city>Salford</city>
        <zip>M6 8HD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <results_first_submitted>July 20, 2022</results_first_submitted>
  <results_first_submitted_qc>August 18, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 14, 2022</results_first_posted>
  <last_update_submitted>August 18, 2022</last_update_submitted>
  <last_update_submitted_qc>August 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Symptomatic Neurogenic Orthostatic Hypotension</keyword>
  <keyword>symptomatic nOH</keyword>
  <keyword>multiple system atrophy</keyword>
  <keyword>MSA</keyword>
  <keyword>Parkinson's disease</keyword>
  <keyword>PD</keyword>
  <keyword>pure autonomic failure</keyword>
  <keyword>PAF</keyword>
  <keyword>primary autonomic failure</keyword>
  <keyword>SEQUOIA</keyword>
  <keyword>ampreloxetine</keyword>
  <keyword>low blood pressure</keyword>
  <keyword>dizziness</keyword>
  <keyword>fainting</keyword>
  <keyword>blacking out</keyword>
  <keyword>lightheadedness</keyword>
  <keyword>norepinephrine</keyword>
  <keyword>hypotension</keyword>
  <keyword>Parkinsonism</keyword>
  <keyword>TD-9855</keyword>
  <keyword>Neurogenic Orthostatic Hypotension</keyword>
  <keyword>nOH</keyword>
  <keyword>0145</keyword>
  <keyword>145</keyword>
  <keyword>169</keyword>
  <keyword>0169</keyword>
  <keyword>TD9855</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension, Orthostatic</mesh_term>
    <mesh_term>Pure Autonomic Failure</mesh_term>
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.</ipd_description>
  </patient_data>
  <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>August 5, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03750552/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>July 19, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03750552/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>195 participants were enrolled across 76 sites in Australia, Austria, Bulgaria, Canada, Denmark, Estonia, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, Spain, Russia, Ukraine, United Kingdom and the United States.</recruitment_details>
      <pre_assignment_details>Overall, 194 randomized participants received at least one dose of study drug. Eight participants from one site were excluded from all analysis sets except the Randomized Analysis Set due to data integrity concerns.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ampreloxetine</title>
          <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received placebo QD for 4 weeks. Placebo: Oral tablet, QD</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="98"/>
                <participants group_id="P2" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
                <participants group_id="P2" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="94"/>
                <participants group_id="P2" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="90"/>
                <participants group_id="P2" count="95"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Baseline Analysis Population includes all participants from the Randomized Analysis Set.</population>
      <group_list>
        <group group_id="B1">
          <title>Ampreloxetine</title>
          <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants received placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="98"/>
            <count group_id="B2" value="97"/>
            <count group_id="B3" value="195"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&lt; 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="72"/>
                    <measurement group_id="B3" value="142"/>
                  </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="37"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="91"/>
                    <measurement group_id="B3" value="183"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="96"/>
                    <measurement group_id="B2" value="94"/>
                    <measurement group_id="B3" value="190"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4</title>
        <description>OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
        <time_frame>Baseline and Week 4</time_frame>
        <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ampreloxetine</title>
            <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4</title>
          <description>OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
          <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, were included in this analysis.</population>
          <units>score 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="94"/>
                <count group_id="O2" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.69" spread="0.290"/>
                    <measurement group_id="O2" value="-1.45" spread="0.293"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.574</p_value>
            <method>Mixed Model Repeated Measures</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.23</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.413</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.05</ci_lower_limit>
            <ci_upper_limit>0.58</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4</title>
        <description>OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
        <time_frame>Baseline and Week 4</time_frame>
        <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, with a valid composite OHSA score at Week 4 were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ampreloxetine</title>
            <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4</title>
          <description>OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
          <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, with a valid composite OHSA score at Week 4 were included in this analysis.</population>
          <units>score 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="90"/>
                <count group_id="O2" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.32" spread="0.200"/>
                    <measurement group_id="O2" value="-1.05" spread="0.202"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.331</p_value>
            <method>Mixed Model Repeated Measures</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.28</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.284</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.84</ci_lower_limit>
            <ci_upper_limit>0.28</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4</title>
        <description>OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
        <time_frame>Baseline and Week 4</time_frame>
        <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, with a valid composite OHDAS score at Week 4 were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ampreloxetine</title>
            <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4</title>
          <description>OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.&#xD;
A mean negative change from baseline indicates a better outcome.</description>
          <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, with a valid composite OHDAS score at Week 4 were included in this analysis.</population>
          <units>score 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="87"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.22" spread="0.265"/>
                    <measurement group_id="O2" value="-0.95" spread="0.267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.481</p_value>
            <method>Mixed Model Repeated Measures</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.27</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.376</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.01</ci_lower_limit>
            <ci_upper_limit>0.48</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4</title>
        <description>PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.</description>
        <time_frame>Baseline and Week 4</time_frame>
        <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, who have available data were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ampreloxetine</title>
            <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants receives placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4</title>
          <description>PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.</description>
          <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, who have available data were included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="91"/>
                <count group_id="O2" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.740</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>Stratified by disease type</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.02</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.073</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.12</ci_lower_limit>
            <ci_upper_limit>0.17</ci_upper_limit>
            <estimate_desc>The assumed common risk difference estimate and standard error are calculated using Mantel-Haenszel stratum weights and the Sato variance estimator. Mantel-Haenszel confidence limits are shown.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced at Least One Fall</title>
        <time_frame>Up to Week 4</time_frame>
        <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, who have available data were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ampreloxetine</title>
            <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced at Least One Fall</title>
          <population>Participants included in the Full Analysis Set, defined as all randomized participants who received at least one dose of study medication and had at least 1 post-baseline measurement of Orthostatic Hypotension Symptom Assessment (OHSA) question 1, who have available data were included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0903</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>Stratified by disease type</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.11</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.064</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.02</ci_lower_limit>
            <ci_upper_limit>0.24</ci_upper_limit>
            <estimate_desc>The assumed common risk difference estimate and standard error are calculated using Mantel-Haenszel stratum weights and the Sato variance estimator. Mantel-Haenszel confidence limits are shown.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Day 43</time_frame>
      <desc>Participants in the Safety Analysis set, defined as all randomized subjects who received at least 1 dose of study medication, were included in this analysis.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ampreloxetine</title>
          <description>Participants received ampreloxetine at a dose of 10 mg once daily (QD) for 4 weeks.&#xD;
Ampreloxetine: Oral tablet, QD</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received placebo once daily (QD) for 4 weeks. Placebo: Oral tablet, QD</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (24.0)</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="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" 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="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (24.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="38" 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="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Duodenitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Temperature regulation disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatomegaly</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bacterial disease carrier</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Eye contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Blood urea nitrogen/creatine ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Crystal urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Eosinophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Gastric pH decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Glomerular filtration rate decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Mean cell haemoglobin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Mean cell volume increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Protein urine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" 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="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Neutrophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Rectal cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bulbar palsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dizziness postural</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Disorientation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Bladder pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urinary tract inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Urine flow decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Renal cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Supine hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Monitor</name_or_title>
      <organization>Theravance Biopharma Inc</organization>
      <phone>1-855-633-8479</phone>
      <email>medinfo@theravance.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/NCT03750552
org study id: 0169
secondary id: 2018-003289-15
nct id: NCT03750552
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in
      subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH with up to 4
      weeks of treatment.
A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to
      evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with
      primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH. The study consists of 3
      periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up.
      The trial utilizes an operational design featuring the ability to conduct protocol required
      visits as either in clinic or remote visits (except Screening visit).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4
time frame: Baseline and Week 4
description: OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.
Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.
A mean negative change from baseline indicates a better outcome.
measure: Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4
time frame: Baseline and Week 4
description: OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.
A mean negative change from baseline indicates a better outcome.
measure: Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4
time frame: Baseline and Week 4
description: OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.
A mean negative change from baseline indicates a better outcome.
measure: Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4
time frame: Baseline and Week 4
description: PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.
measure: Number of Participants Who Experienced at Least One Fall
time frame: Up to Week 4
arm group label: ampreloxetine
arm group type: Experimental
description: Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.
intervention type: Drug
intervention name: ampreloxetine
description: Oral tablet, QD
arm group label: ampreloxetine
other name: TD-9855
intervention type: Drug
intervention name: Placebo
description: Oral tablet, QD
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Monitor
role: Study Director
affiliation: Theravance Biopharma
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country: Australia
country: Austria
country: Bulgaria
country: Canada
country: Denmark
country: Estonia
country: France
country: Germany
country: Hungary
country: Israel
country: Italy
country: New Zealand
country: Poland
country: Portugal
country: Russian Federation
country: Spain
country: Ukraine
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Hypotension, Orthostatic
mesh term: Pure Autonomic Failure
mesh term: Hypotension
sharing ipd: No
ipd description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
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certain agreements: 
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