<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/NCT01689246</url>
  </required_header>
  <id_info>
    <org_study_id>TRx-237-015</org_study_id>
    <nct_id>NCT01689246</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease</brief_title>
  <official_title>Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 15-Month Trial of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TauRx Therapeutics Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TauRx Therapeutics Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment&#xD;
      of subjects with mild to moderate Alzheimer's Disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)</measure>
    <time_frame>65 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)</measure>
    <time_frame>65 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes</measure>
    <time_frame>65 weeks</time_frame>
    <description>Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)</measure>
    <time_frame>65 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline on Mini-Mental Status Examination (MMSE)</measure>
    <time_frame>65 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in expected decline of whole brain volume as measured by brain MRI</measure>
    <time_frame>39 weeks and 65 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging</measure>
    <time_frame>39 weeks and 65 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in expected increase in ventricular volume and decline in hippocampal volume as evaluated by MRI</measure>
    <time_frame>39 weeks and 65 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite</measure>
    <time_frame>65 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture</measure>
    <time_frame>65 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided</measure>
    <time_frame>65 weeks</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">891</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>TRx0237 250 mg/day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TRx0237 150 mg/day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TRx0237 150 mg/day</intervention_name>
    <description>TRx0237 75 mg tablets will be administered twice daily.</description>
    <arm_group_label>TRx0237 150 mg/day</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TRx0237 250 mg/day</intervention_name>
    <description>TRx0237 125 mg tablets will be administered twice daily.</description>
    <arm_group_label>TRx0237 250 mg/day</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets will be administered twice daily. The active placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence the placebo group will receive a total of 8 mg/day of TRx0237.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of all cause dementia and probable Alzheimer's disease&#xD;
&#xD;
          -  Clinical Dementia Rating (CDR) total score of 1 (mild) to 2 (moderate) and MMSE score&#xD;
             of 14-26 (inclusive)&#xD;
&#xD;
          -  Age &lt; 90 years&#xD;
&#xD;
          -  Modified Hachinski ischemic score of ≤ 4&#xD;
&#xD;
          -  Females, if of child-bearing potential, must practice true abstinence or be competent&#xD;
             to use adequate contraception and agree to maintain this throughout the study&#xD;
&#xD;
          -  Subject, and/or, in the case of reduced decision-making capacity, legally acceptable&#xD;
             representative(s) consistent with national law is/are able to read, understand, and&#xD;
             provide written informed consent&#xD;
&#xD;
          -  Has one (or more) identified adult caregiver who is willing to provide written&#xD;
             informed consent for his/her own participation; is able to read, understand, and speak&#xD;
             the designated language at the study site; either lives with the subject or sees the&#xD;
             subject for ≥2 hours/day ≥3 days/week; agrees to accompany the subject to each study&#xD;
             visit; and is able to verify daily compliance with study drug&#xD;
&#xD;
          -  If currently taking an acetylcholinesterase inhibitor and/or memantine at the time of&#xD;
             Screening, the subject must have been taking such medication(s) for ≥3 months. The&#xD;
             dosage regimen must have remained stable for ≥6 weeks and it must be planned to remain&#xD;
             stable throughout participation in the study.&#xD;
&#xD;
          -  Able to comply with the study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant central nervous system (CNS) disorder other than Alzheimer's disease&#xD;
&#xD;
          -  Significant focal or vascular intracranial pathology seen on brain MRI scan&#xD;
&#xD;
          -  Clinical evidence or history of stroke, transient ischemic attack, significant head&#xD;
             injury or other unexplained or recurrent loss of consciousness ≥15 minutes&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar&#xD;
             disorder, or substance (including alcohol) related disorders&#xD;
&#xD;
          -  Metal implants in the head (except dental), pacemaker, cochlear implants, or any other&#xD;
             non-removable items that are contraindications to MRI&#xD;
&#xD;
          -  Resides in hospital or moderate to high dependency continuous care facility&#xD;
&#xD;
          -  History of swallowing difficulties&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase deficiency&#xD;
&#xD;
          -  History of significant hematological abnormality or current acute or chronic&#xD;
             clinically significant abnormality&#xD;
&#xD;
          -  Abnormal serum chemistry laboratory value at Screening deemed to be clinically&#xD;
             relevant by the investigator&#xD;
&#xD;
          -  Clinically significant cardiovascular disease or abnormal assessments&#xD;
&#xD;
          -  Preexisting or current signs or symptoms of respiratory failure&#xD;
&#xD;
          -  Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine&#xD;
             disease (not adequately treated) and/or other unstable or major disease other than&#xD;
             Alzheimer's disease&#xD;
&#xD;
          -  Diagnosis of cancer within the past 2 years prior to Baseline (other than basal cell&#xD;
             or squamous cell skin cancer or Stage 1 prostate cancer) unless treatment has resulted&#xD;
             in complete freedom from disease for at least 2 years&#xD;
&#xD;
          -  Prior intolerance or hypersensitivity to methylthioninium-containing drug, similar&#xD;
             organic dyes, or any of the excipients&#xD;
&#xD;
          -  Treatment currently or within 3 months before Baseline with any of the following&#xD;
             medications:&#xD;
&#xD;
               -  Tacrine&#xD;
&#xD;
               -  Clozapine, olanzapine (and there is no intent to initiate therapy during the&#xD;
                  course of the study)&#xD;
&#xD;
               -  Carbamazepine, primidone&#xD;
&#xD;
               -  Drugs with a warning or precaution in the labeling about methemoglobinemia at&#xD;
                  approved doses&#xD;
&#xD;
          -  Current or prior participation in a clinical trial as follows:&#xD;
&#xD;
               -  Clinical trial of a product for cognition within 3 months of Screening (unless&#xD;
                  confirmed to have been randomized to placebo)&#xD;
&#xD;
               -  A clinical trial of a drug, biologic, therapeutic device, or medical food in&#xD;
                  which the last dose/administration was received within 28 days prior to Baseline&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Xenoscience, Inc/ 21st Century Neurology</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Feldman, Robert MD</name>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shankle Clinic and Hoag Memorial Hospital Presbyterian</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92658</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Research Network</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco Clinical Research Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JEM Research</name>
      <address>
        <city>Atlantis</city>
        <state>Florida</state>
        <zip>33462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Matters Research</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33445</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNS Healthcare, Inc</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Research, LLC-North Clinic</name>
      <address>
        <city>Leesburg</city>
        <state>Florida</state>
        <zip>34748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Research Associates</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Research, LLC</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>iResearch Atlanta</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Neurosciences Institute</name>
      <address>
        <city>Elk Grove</city>
        <state>Illinois</state>
        <zip>60007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ActivMed Practices &amp; Research</name>
      <address>
        <city>Methuen</city>
        <state>Massachusetts</state>
        <zip>01844</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Olive Branch Family Medical</name>
      <address>
        <city>Olive Branch</city>
        <state>Mississippi</state>
        <zip>38654</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memory Enhancement Centers of America, Inc</name>
      <address>
        <city>Eatontown</city>
        <state>New Jersey</state>
        <zip>07724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRI Worldwide</name>
      <address>
        <city>Marlton</city>
        <state>New Jersey</state>
        <zip>08053</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cognitive Research Center of New Jersey</name>
      <address>
        <city>Springfield</city>
        <state>New Jersey</state>
        <zip>07801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Memory Research Institute of NJ PC</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08757</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurological Associates of Albany, P. C.</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPRI</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurobehavioral Clinical Research</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Clinical Trial Center, LLC</name>
      <address>
        <city>Jenkintown</city>
        <state>Pennsylvania</state>
        <zip>19046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FutureSearch Trials of Neurology</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Division of Rehabilitation and Aged Care</name>
      <address>
        <city>Hornsby</city>
        <state>New South Wales</state>
        <zip>2077</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Neurology Pty Limited</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Department for Old Age Psychiatry, Prince of Wales Hospital</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Discipline of Psychiatry, University of Qld</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4006</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital Memory Trials Centre</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memory Unit, Neurology, The Queen Elizabeth Hospital</name>
      <address>
        <city>Woodville South</city>
        <state>South Australia</state>
        <zip>5011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital</name>
      <address>
        <city>Heidelberg West</city>
        <state>Victoria</state>
        <zip>3081</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McCusker Alzheimer's Research Foundation Inc</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurodegenerative Disorders Research Pty Ltd</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6005</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT &quot;Alexandrovska&quot; Clinic of Neurology Diseases Department of Neurodegenerative and Immune and Infectious Diseases of Central Nervous System with Sector for Treatment of Neuroinfections</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT &quot;Alexandrovska&quot; Clinic of Psychiatry First Department of Psychiatry</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Okanagan Clinical Trials</name>
      <address>
        <city>Kelowna</city>
        <state>British Columbia</state>
        <zip>V1Y 1Z9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>True North Clinical Research Kentville Inc</name>
      <address>
        <city>Kentville</city>
        <state>Nova Scotia</state>
        <zip>B4N 4K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Memory Program</name>
      <address>
        <city>North York</city>
        <state>Ontario</state>
        <zip>M3B 2S7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Centre Zagreb</name>
      <address>
        <city>Zagreb</city>
        <zip>10000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Psychiatric Hospital Vrapce</name>
      <address>
        <city>Zagreb</city>
        <zip>10090</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurozentrum Achim Dr. med. Andreas Mahler</name>
      <address>
        <city>Achim</city>
        <zip>28832</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité, University Medicine Berlin, CBF, Neurology</name>
      <address>
        <city>Berlin</city>
        <zip>12200</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memory Clinic, ECRC</name>
      <address>
        <city>Berlin</city>
        <zip>13125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurologia Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Neurologico Carlo Besta</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto neurologico Casimiro Mondino</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Neurologica, Università di Perugia-Ospedale S. Maria della Misericordia</name>
      <address>
        <city>Perugia</city>
        <zip>06156</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universita' Cattolica del Sacro Cuore</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Sant'Andrea di Roma- Unita' di Neurologia</name>
      <address>
        <city>Roma</city>
        <zip>00189</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dipartimento di Neuroscienze Universita' di Torino</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S.maria Della Misericordia</name>
      <address>
        <city>Udine</city>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U.O. Di Neurologia Ospedale di Circolo e Fondazione Macchi</name>
      <address>
        <city>Varese</city>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dong-A Medical Center</name>
      <address>
        <city>Busan</city>
        <zip>602-715</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inha University Hospital</name>
      <address>
        <city>Incheon</city>
        <zip>400-711</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gachon University Gil Medical Center</name>
      <address>
        <city>Incheon</city>
        <zip>405-760</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>463-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inje University Sanggye Paik Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>139-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Konkuk University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>143-729</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Boramae Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>156-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Kuala Lumpur Royal College of Medicine</name>
      <address>
        <city>Ipoh</city>
        <zip>30450</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sultan Ismail</name>
      <address>
        <city>Johor Bahru</city>
        <zip>81100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Malaya Medical Centre</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50603</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taiping Hospital</name>
      <address>
        <city>Taiping</city>
        <zip>34000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Podlaskie Centrum Psychogeriatrii</name>
      <address>
        <city>Białystok</city>
        <zip>15-756</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pallmed sp zoo prowadząca NZOZ Dom Sue Ryder; Centrum Psychoneurologii Wieku Podeszłego</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-796</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS</name>
      <address>
        <city>Katowice</city>
        <zip>40-123</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabinet Neurologiczny, Indywidualna Specjalistyczna Praktyka Lekarska</name>
      <address>
        <city>Mosina</city>
        <zip>62-050</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy</name>
      <address>
        <city>Poznań</city>
        <zip>61-853</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Euromedis Sp. z o.o.</name>
      <address>
        <city>Szczecin</city>
        <zip>70-111</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Usługi Lekarskie Sp.c Palasik, Żabierek</name>
      <address>
        <city>Warszawa</city>
        <zip>00-669</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>mMED</name>
      <address>
        <city>Warszawa</city>
        <zip>01-697</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MTZ Clinical Research Sp. z o.o.</name>
      <address>
        <city>Warszawa</city>
        <zip>02-106</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>County Emergency Clinical Hospital Arad, Psychiatry Department</name>
      <address>
        <city>Arad</city>
        <zip>310022</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CMDTA &quot;Neomed&quot;</name>
      <address>
        <city>Brasov</city>
        <zip>500283</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Emergency Central Military Hospital &quot;Dr.Carol Davila&quot;, Psychiatry Department</name>
      <address>
        <city>Bucharest</city>
        <zip>010816</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychomedical Consult</name>
      <address>
        <city>Bucharest</city>
        <zip>024072</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Municipal Hospital &quot;Dr. Gavril Curteanu&quot;, Psychiatry Department</name>
      <address>
        <city>Oradea</city>
        <zip>410154</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychiatry Hospital &quot;Dr. Gheorghe Preda&quot;, Center of Mental Health</name>
      <address>
        <city>Sibiu</city>
        <zip>550082</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychiatry Hospital &quot;Dr. Gheorghe Preda&quot;, Department of Psychiatry III</name>
      <address>
        <city>Sibiu</city>
        <zip>550082</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emergency Clinical County Hospital Sibiu, Neurology Department</name>
      <address>
        <city>Sibiu</city>
        <zip>550166</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Healthcare Institution of Sverdlovsk region &quot;Sverdlovsk Regional Clinical Psychiatric Hospital&quot;</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Non-governmental Healthcare Institution &quot;Central Clinical Hospital #6 of the JSC &quot;Russian Railways&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>109388</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department</name>
      <address>
        <city>Moscow</city>
        <zip>115522</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Research Center of the Russian Academy of Medical Sciences</name>
      <address>
        <city>Moscow</city>
        <zip>115522</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CityClinical Hospital #34, City Scientific Practical Neurological Center</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Geriatric Medical and Social Center</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>190103</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Nicholas Psychiatric Hospital</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>190121</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>192019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital (NUH)</name>
      <address>
        <city>Singapore</city>
        <zip>119223</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Neuroscience Institute (NNI)</name>
      <address>
        <city>Singapore</city>
        <zip>308433</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tan Tock Seng Hospital (TTSH)</name>
      <address>
        <city>Singapore</city>
        <zip>308433</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changi General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>529889</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Ceuta</name>
      <address>
        <city>Ceuta</city>
        <zip>51003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Reina Sofía</name>
      <address>
        <city>Córdoba</city>
        <zip>14011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Viamed Montecanal</name>
      <address>
        <city>Zaragoza</city>
        <zip>50006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changhua Christian Hospital</name>
      <address>
        <city>Changhua</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Kaohsiung</name>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>En Chu Kong Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Yang-Ming University School of Medicine</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Linkou</name>
      <address>
        <city>Taoyuan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Grampian, Department of Old Age Psychiatry Royal Cornhill Hospital</name>
      <address>
        <city>Aberdeen</city>
        <zip>AB25 2ZH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RICE - The Research Institute for the Care of Older People</name>
      <address>
        <city>Bath</city>
        <zip>BA1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Belfast Health and Social Care Trust (BHSCT)</name>
      <address>
        <city>Belfast</city>
        <zip>BT12 6BA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Barberry Centre</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2SG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research Ltd</name>
      <address>
        <city>Blackpool</city>
        <zip>FY2 0JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research Ltd</name>
      <address>
        <city>Bradford</city>
        <zip>BD3 0DQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research Ltd</name>
      <address>
        <city>Cannock</city>
        <zip>WS11 0BN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research Ltd</name>
      <address>
        <city>Leeds</city>
        <zip>LS10 1DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Re: Cognition Health Ltd.</name>
      <address>
        <city>London</city>
        <zip>W1G 9JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charing Cross Hospital</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dementia Research Centre</name>
      <address>
        <city>London</city>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research Ltd</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9NQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Croatia</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.AlzheimersStudies.com</url>
    <description>Alzheimer's Survey</description>
  </link>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <disposition_first_submitted>March 12, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>March 12, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 14, 2018</disposition_first_posted>
  <last_update_submitted>March 12, 2018</last_update_submitted>
  <last_update_submitted_qc>March 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>Alzheimer Disease</keyword>
  <keyword>TRx0237</keyword>
  <keyword>AD</keyword>
  <keyword>Neurodegenerative Diseases</keyword>
  <keyword>Dementia</keyword>
  <keyword>Brain Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylene Blue</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01689246
org study id: TRx-237-015
nct id: NCT01689246
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment
      of subjects with mild to moderate Alzheimer's Disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)
time frame: 65 weeks
measure: Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)
time frame: 65 weeks
measure: Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes
time frame: 65 weeks
description: Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity
measure: Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
time frame: 65 weeks
measure: Change from Baseline on Mini-Mental Status Examination (MMSE)
time frame: 65 weeks
measure: Change in expected decline of whole brain volume as measured by brain MRI
time frame: 39 weeks and 65 weeks
measure: Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
time frame: 39 weeks and 65 weeks
measure: Change in expected increase in ventricular volume and decline in hippocampal volume as evaluated by MRI
time frame: 39 weeks and 65 weeks
measure: Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite
time frame: 65 weeks
measure: Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture
time frame: 65 weeks
measure: Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided
time frame: 65 weeks
arm group label: TRx0237 250 mg/day
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: TRx0237 150 mg/day
arm group type: Experimental
intervention type: Drug
intervention name: TRx0237 150 mg/day
description: TRx0237 75 mg tablets will be administered twice daily.
arm group label: TRx0237 150 mg/day
intervention type: Drug
intervention name: TRx0237 250 mg/day
description: TRx0237 125 mg tablets will be administered twice daily.
arm group label: TRx0237 250 mg/day
intervention type: Drug
intervention name: Placebo
description: Placebo tablets will be administered twice daily. The active placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence the placebo group will receive a total of 8 mg/day of TRx0237.
arm group label: Placebo
criteria: 
gender: All
minimum age: N/A
maximum age: 89 Years
healthy volunteers: No
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country: Australia
country: Bulgaria
country: Canada
country: Croatia
country: Germany
country: Italy
country: Korea, Republic of
country: Malaysia
country: Poland
country: Romania
country: Russian Federation
country: Singapore
country: Spain
country: Taiwan
country: United Kingdom
country: United States
url: http://www.AlzheimersStudies.com
description: Alzheimer's Survey
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Methylene Blue