<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/NCT01677754</url>
  </required_header>
  <id_info>
    <org_study_id>BP28248</org_study_id>
    <secondary_id>2012-000943-29</secondary_id>
    <nct_id>NCT01677754</nct_id>
  </id_info>
  <brief_title>A Study of RO4602522 in Participants With Moderate Severity Alzheimer Disease on Background Alzheimer Disease Therapy</brief_title>
  <acronym>MAyflOwer RoAD</acronym>
  <official_title>A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of RO4602522 Added to Background Alzheimer's Disease Therapy in Patients With Moderate Severity Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled&#xD;
      study will evaluate the efficacy and safety of RO4602522 in participants with moderate&#xD;
      severity Alzheimer's disease. Participants who are taking background therapy of&#xD;
      acetylcholinesterase inhibitors (AChEI) alone or in combination with memantine for at least 4&#xD;
      months before screening will be randomized to receive either one of two doses of RO4602522 or&#xD;
      placebo for 12 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 24, 2012</start_date>
  <completion_date type="Actual">June 12, 2015</completion_date>
  <primary_completion_date type="Actual">June 12, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (&lt;=) 4 Points in ADAS-Cog-11</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Worsening in BEHAVE-AD-FW Score</measure>
    <time_frame>Baseline to Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Worsening in ADCS-CGIC Score</measure>
    <time_frame>Baseline to Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months</measure>
    <time_frame>Baseline, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Adverse Events</measure>
    <time_frame>Baseline up to 13 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Change in Lens Opacity Grading</measure>
    <time_frame>Baseline; Months 6, and 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Abnormal Visual Acuity Test Results</measure>
    <time_frame>Baseline, Months 6, and 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Michigan Neuropathy Screening Instrument Score</measure>
    <time_frame>Baseline, Weeks 8, 18, 30, 44, 52, and at the last follow-up visit (12 weeks after last dose, up to 64 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Receiving Concomitant Medications</measure>
    <time_frame>Baseline to 13 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Total Clearance of the Drug From Plasma After Administration of RO4602522</measure>
    <time_frame>Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution at Steady State after Administration of RO4602522</measure>
    <time_frame>Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve of RO4602522</measure>
    <time_frame>Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration of RO4602522</measure>
    <time_frame>Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">542</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RO4602522 1 milligram (mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive RO4602522 1 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RO4602522 5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive RO4602522 5 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO4602522</intervention_name>
    <description>Participants will receive RO4602522 orally once daily for 12 months.</description>
    <arm_group_label>RO4602522 1 milligram (mg)</arm_group_label>
    <arm_group_label>RO4602522 5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive placebo for RO4602522 orally once daily for 12 months.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donepezil</intervention_name>
    <description>Stable dose as background medication</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>RO4602522 1 milligram (mg)</arm_group_label>
    <arm_group_label>RO4602522 5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Memantine</intervention_name>
    <description>Stable dose as background medication in combination with AChEIs</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>RO4602522 1 milligram (mg)</arm_group_label>
    <arm_group_label>RO4602522 5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivastigmine</intervention_name>
    <description>Stable dose as background medication</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>RO4602522 1 milligram (mg)</arm_group_label>
    <arm_group_label>RO4602522 5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Galantamine</intervention_name>
    <description>Stable dose as background medication</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>RO4602522 1 milligram (mg)</arm_group_label>
    <arm_group_label>RO4602522 5 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Probable Alzheimer disease, based on the National Institute of Neurological and&#xD;
             Communicative Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders&#xD;
             Association (ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Fourth&#xD;
             Edition (DSM-IV-TR) criteria&#xD;
&#xD;
          -  Mini-Mental State Exam (MMSE) score at screening between 13 and 20, inclusive&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 36 kilograms per square meter (kg/m^2)&#xD;
             (inclusive) at screening&#xD;
&#xD;
          -  Modified Hachinski Ischemia Score of less than or equal to (&lt;/=) 4&#xD;
&#xD;
          -  Participants with Cornell Scale for Depression in Dementia (CSDD) scores &lt;/= 13 at&#xD;
             screening&#xD;
&#xD;
          -  Receiving treatment with donepezil, rivastigmine, galantamine or any AChEIs in&#xD;
             combination with memantine for at least 4 months before screening, with their dose and&#xD;
             formulation stabilized at least 3 months before screening. All formulation and dosages&#xD;
             are allowed except donezepil 23 mg (alone or in combination)&#xD;
&#xD;
          -  Females of childbearing potential must have a negative pregnancy test and must agree&#xD;
             to use effective contraception&#xD;
&#xD;
          -  Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane)&#xD;
&#xD;
          -  Have a reliable caregiver or some other identified responsible person who has frequent&#xD;
             contact with the participant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any neurological or psychiatric condition that may occur currently or during the&#xD;
             course of the study that can impair cognition or functioning that is not associated&#xD;
             with Alzheimer's disease&#xD;
&#xD;
          -  Background of mental retardation&#xD;
&#xD;
          -  Uncontrolled behavioral symptoms incompatible with compliance or evaluability&#xD;
&#xD;
          -  Alcohol and/or substance abuse or dependence (DSM-IV-TR) in the past 2 years, except&#xD;
             nicotine use which is allowed. However, smokers treated with nicotine replacement&#xD;
             therapy or bupropion are excluded&#xD;
&#xD;
          -  Unstable or poorly controlled hypertension as assessed by the investigator regardless&#xD;
             of whether or not the participant is taking antihypertensive medications&#xD;
&#xD;
          -  Unstable or clinically significant cardiovascular disease that could be expected to&#xD;
             progress, recur, or change during study period to such an extent that it could bias&#xD;
             the assessment of the clinical or mental status of the participant&#xD;
&#xD;
          -  Inadequate hepatic, renal or thyroid function&#xD;
&#xD;
          -  Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Poorly controlled diabetes (glycosylated hemoglobin [HbA1c] greater than or equal to&#xD;
             [&gt;/=] 9 percent at screening)&#xD;
&#xD;
          -  Requiring nursing home care. Participants living in assisted living facilities are&#xD;
             allowed if a reliable caregiver is available (see inclusion criteria)&#xD;
&#xD;
          -  Current treatment for Alzheimer's disease other than those listed in inclusion&#xD;
             criteria&#xD;
&#xD;
          -  Participation at any time in an active Alzheimer's disease vaccine study&#xD;
&#xD;
          -  Participation in a passive Alzheimer's disease immunization study less than 1 year&#xD;
             before screening except for a) participants where documented medical history indicate&#xD;
             that they were randomized to the placebo group in these studies, b) participants&#xD;
             treated with bapineuzumab where a 6-month exclusion period applies&#xD;
&#xD;
          -  Recent (&lt;/= 12 weeks) or concomitant use of other Monoamine oxidase inhibitors&#xD;
             (selective or not) including selegiline or rasagiline&#xD;
&#xD;
          -  Antidepressant treatments are not allowed except for citalopram up to 20 mg daily,&#xD;
             escitalopram up to 10 mg daily, paroxetine up to 30 mg daily, sertraline up to 100 mg&#xD;
             daily and trazodone up to 100 mg daily. If treated with one of these antidepressants,&#xD;
             the treatment should be present for at least 6 weeks at screening. All other&#xD;
             antidepressants including other SSRIs, tricyclic antidepressants (TCAs),&#xD;
             serotonin-norepinephrine reuptake inhibitors (SNRIs), St. John's wort and bupropion&#xD;
             are excluded&#xD;
&#xD;
          -  Anti-psychotic use within 4 weeks before screening is not permitted except risperidone&#xD;
             up to 1.5 mg/day, quetiapine up to 100 milligrams per day (mg/day), olanzapine up to 5&#xD;
             mg/day, and aripiprazole up to 10 mg daily&#xD;
&#xD;
          -  Anxiolytics/ hypnotics use is not permitted except for benzodiazepines of short or&#xD;
             intermediate half-life for anxiety/sleeping disorders. Zolpidem (up to 5 mg/day),&#xD;
             zopiclone (up to 7.5 mg/day), eszopiclone (up to 2 mg/day), trazodone (up to 50&#xD;
             mg/day, at bedtime) or zaleplon (up to 5 mg/day) is permitted for insomnia&#xD;
&#xD;
          -  Anti-Parkinson's agents within 2 weeks before screening are not permitted&#xD;
&#xD;
          -  Recent (less than 4 weeks prior to screening) or concomitant use of anticonvulsants&#xD;
&#xD;
          -  Anticholinergics/ antihistaminics within 2 weeks before screening are not permitted,&#xD;
             except i) if used episodically more than 3 days before the screening cognitive&#xD;
             measurement, ii) non-sedating antihistaminic medications (without anticholinergic&#xD;
             effects such as cetirizine) or peripheral anticholinergics without central&#xD;
             anticholinergic effects (such as, trospium for the treatment of hyperactive bladder),&#xD;
             which are permitted&#xD;
&#xD;
          -  Recent (less than 1 week prior to screening) or concomitant use of opioid drugs&#xD;
             (tramadol, methadone, propoxyphene, or meperidine), cyclobenzaprine and&#xD;
             dextromethorphan&#xD;
&#xD;
          -  Concomitant use of sympathomimetic drugs, including sympathomimetics in local&#xD;
             anesthetics and ephedra supplements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Advanced Research Center, Inc.;In-Patient Unit</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Center of North Orange County</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Clinical Research</name>
      <address>
        <city>Lomita</city>
        <state>California</state>
        <zip>90717</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Artemis Institute for Clinical Research, LLC</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Mesa Vista Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</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>94109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurological Research Inst</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90025</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>Research Center for Clinical Studies, Inc.</name>
      <address>
        <city>Norwalk</city>
        <state>Connecticut</state>
        <zip>06851</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease and Movement Disorders Center of Boca Raton</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Brooksville</city>
        <state>Florida</state>
        <zip>34601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Matters Research, Inc.</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33445</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurologic Consultants, P.A.</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galiz Research, LLC</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Jewish Health Systems</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33137</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research Group of Central Florida</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>3273</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Research East, LLC</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Clinical Development, Inc.- St. Petersburg, FL</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33716</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Axiom Clinical Research of Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premiere Research Institute</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33407</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>NeuroStudies.net, LLC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Brothers Neurosci Inst</name>
      <address>
        <city>Elk Grove Village</city>
        <state>Illinois</state>
        <zip>60007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana Research Associates</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Booker, J. Gary, MD, APMC</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71104-2136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern Michigan Neurology</name>
      <address>
        <city>Traverse City</city>
        <state>Michigan</state>
        <zip>49684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hattiesburg Clinic</name>
      <address>
        <city>Hattiesburg</city>
        <state>Mississippi</state>
        <zip>39401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Psychiatric Associates, LLC</name>
      <address>
        <city>Creve Coeur</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memory Enhancement Center 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>Albuquerque Neuroscience Inc.</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University Medical Center;Child Study Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richmond Behavioral Associates</name>
      <address>
        <city>Staten Island</city>
        <state>New York</state>
        <zip>10312</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raleigh Neurology Associates</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607-6520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PMG Research of Winston-Salem, LLC</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Health Science Institute</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cutting Edge Research Group</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73116</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>Radiant Research, Inc.</name>
      <address>
        <city>Wyomissing</city>
        <state>Pennsylvania</state>
        <zip>19610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Mood &amp; Memory Research Institute</name>
      <address>
        <city>East Providence</city>
        <state>Rhode Island</state>
        <zip>02914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimer's Research &amp; Clinical Programs</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Texas Health Science Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Sydney</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Coast Neurosciences Research</name>
      <address>
        <city>Erina</city>
        <state>New South Wales</state>
        <zip>2250</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Neurology</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Woodville</city>
        <state>South Australia</state>
        <zip>5011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Box Hill Hospital; Eastern Clinical Research Unit</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.G.Mander Pty Ltd</name>
      <address>
        <city>Geelong</city>
        <state>Victoria</state>
        <zip>3220</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heidelberg Repatriation Hospital</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hollywood Specialist Centre</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurodegenerative Disorders Research</name>
      <address>
        <city>Subiaco</city>
        <state>Western Australia</state>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Medical Arts Health Research Group</name>
      <address>
        <city>Powell River</city>
        <state>British Columbia</state>
        <zip>V8A 3B6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver Hospital - UBC Hospital Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6T 2B5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver Island Health Authority</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <zip>V8R 1J8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capitol District Health Authority</name>
      <address>
        <city>Halilfax</city>
        <state>Nova Scotia</state>
        <zip>B3H 2E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>True North Clinical Research Kentville</name>
      <address>
        <city>Kentville</city>
        <state>Nova Scotia</state>
        <zip>B4N 4K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jbn Medical Diagnostic Services Inc.</name>
      <address>
        <city>Burlington</city>
        <state>Ontario</state>
        <zip>L7M 4Y1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bruyere Continuing Care</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1N 5C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ingram, Jennifer MD</name>
      <address>
        <city>Peterborough</city>
        <state>Ontario</state>
        <zip>K9H 3S1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Memory Program (Neurology Research Inc.)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M3B 2S7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Centre for Memory and Aging</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4G 3E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Sunnybrook Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Recherches Neuro-Hippocame</name>
      <address>
        <city>Gatineau</city>
        <state>Quebec</state>
        <zip>J8T 8J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Neuro Rive-Sud</name>
      <address>
        <city>Greenfield Park</city>
        <state>Quebec</state>
        <zip>J4V 2J2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de gériatrie de Sherbrooke; Service de gériatrie/pavillon Argyll</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1J 3H5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric</name>
      <address>
        <city>Verdun</city>
        <state>Quebec</state>
        <zip>H4H 1R3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Quebec - Hôpital de l' Enfant Jésus</name>
      <address>
        <city>Quebec</city>
        <zip>G1J 1Z4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEUROHK s.r.o.</name>
      <address>
        <city>Chocen</city>
        <zip>565 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>P-P Klinika</name>
      <address>
        <city>Kladno</city>
        <zip>272 80</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Supervize s.r.o.</name>
      <address>
        <city>Kutna Hora - Vnitrni Mesto</city>
        <zip>284 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemocnice Na Bulovce</name>
      <address>
        <city>Prague</city>
        <zip>180 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clintrial,s.r.o.</name>
      <address>
        <city>Praha 10</city>
        <zip>100 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AD71 s.r.o.</name>
      <address>
        <city>Praha 10</city>
        <zip>102 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomayerova nemocnice</name>
      <address>
        <city>Praha 4 - Krc</city>
        <zip>140 59</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Psychiatry Trial s.r.o.</name>
      <address>
        <city>Praha 5</city>
        <zip>158 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurologicka ambulance</name>
      <address>
        <city>Praha 6</city>
        <zip>16000</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FORBELI s.r.o.</name>
      <address>
        <city>Praha 6</city>
        <zip>165 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de la côte Basque</name>
      <address>
        <city>Bayonne</city>
        <zip>64109</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Neurologique Pierre Wertheimer</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Nord Laënnec - CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cimiez; CMRR</name>
      <address>
        <city>Nice</city>
        <zip>06003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Sud - Hôpital Xavier Arnozan</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Maison Blanche</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Rennes - Hopital Hôtel Dieu</name>
      <address>
        <city>Rennes</city>
        <zip>35064</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse - La Grave</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Tours - Hôpital Bretonneau</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de Brabois Adultes</name>
      <address>
        <city>Vandoeuvre-les-nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital des Charpennes</name>
      <address>
        <city>Villeurbanne</city>
        <zip>69100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gemeinschaftspraxis</name>
      <address>
        <city>Ellwangen</city>
        <zip>73479</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henriettenstiftung Hannover</name>
      <address>
        <city>Hannover</city>
        <zip>30559</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ISPG - Institut fuer Studien zur Psychischen Gesundheit</name>
      <address>
        <city>Mannheim</city>
        <zip>68165</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum rechts der Isar der Technischen Universität München</name>
      <address>
        <city>Munchen</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung</name>
      <address>
        <city>Siegen</city>
        <zip>57072</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nuovo Ospedale Civile S.Agostino - Estense</name>
      <address>
        <city>Modena</city>
        <state>Emilia-Romagna</state>
        <zip>41126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Agostino Gemelli; Farmacia</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Santa Lucia IRCCS</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00179</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Umberto I Policlinico di Roma-Università di Roma La Sapienza</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00185</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ente Ospedaliero Ospedali Galliera</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università degli Studi di Genova</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università degli studi di Perugia</name>
      <address>
        <city>Perugia</city>
        <state>Umbria</state>
        <zip>06126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dong-A University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>49201</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <zip>443-380</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inha University Hospital; Pulmonary Medicine</name>
      <address>
        <city>Incheon</city>
        <zip>400-711</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyung Hee University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02447</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Konkuk University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05030</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Podlaskie Centrum Psychogeriatrii</name>
      <address>
        <city>Bialystok</city>
        <zip>15-732</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne</name>
      <address>
        <city>Gdansk</city>
        <zip>80-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specjal. Praktyka Lekarska; Prof. Grzegorz Opala</name>
      <address>
        <city>Katowice</city>
        <zip>40-588</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne Dendryt</name>
      <address>
        <city>Katowice</city>
        <zip>40-684</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek</name>
      <address>
        <city>Poznan</city>
        <zip>61-289</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Syntonia</name>
      <address>
        <city>Pruszcz Gdanski</city>
        <zip>83-000</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog</name>
      <address>
        <city>Sopot</city>
        <zip>81-717</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>mMED Maciej Czarnecki</name>
      <address>
        <city>Warszawa</city>
        <zip>01-697</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Psychiatrii i Neurologii</name>
      <address>
        <city>Warszawa</city>
        <zip>02-957</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Elche; Servicio de Farmacia</name>
      <address>
        <city>Elche</city>
        <state>Alicante</state>
        <zip>03203</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundació ACE</name>
      <address>
        <city>BArcelon</city>
        <state>Barcelona</state>
        <zip>08034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General De Catalunya; Servicio de Neurologia</name>
      <address>
        <city>Sant Cugat del Valles</city>
        <state>Barcelona</state>
        <zip>8195</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro Majadahonda</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen del Puerto</name>
      <address>
        <city>Plasencia</city>
        <state>Palencia</state>
        <zip>10600</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Seville</city>
        <state>Sevilla</state>
        <zip>41071</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CAE Oroitu</name>
      <address>
        <city>BaraKaldo</city>
        <state>Vizcaya</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Perpetuo Socorro, Servicio de Geriatria</name>
      <address>
        <city>Albacete</city>
        <zip>2006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo</name>
      <address>
        <city>Malmö</city>
        <zip>205 02</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska Universitetssjukhuset Huddinge</name>
      <address>
        <city>Stockholm</city>
        <zip>171 64</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognitive Treatment &amp; Research Unit</name>
      <address>
        <city>Crowborough</city>
        <zip>TN6 1HB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ninewells Hospital</name>
      <address>
        <city>Dundee</city>
        <zip>DD12 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow Memory Clinic</name>
      <address>
        <city>Glasgow</city>
        <zip>G20 0XA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West London Cognitive Disorders Treatment and Research Unit; Lakeside Metal Health Unit</name>
      <address>
        <city>Isleworth</city>
        <zip>TW7 6FY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Psychiatry</name>
      <address>
        <city>London</city>
        <zip>SE5 8AF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norwich Medical School</name>
      <address>
        <city>Norwich</city>
        <zip>NR4 7UY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memory Service North</name>
      <address>
        <city>Sheffield</city>
        <zip>S35 8QS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <disposition_first_submitted>July 20, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>July 20, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">July 22, 2016</disposition_first_posted>
  <last_update_submitted>May 25, 2017</last_update_submitted>
  <last_update_submitted_qc>May 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Memantine</mesh_term>
    <mesh_term>Rivastigmine</mesh_term>
    <mesh_term>Donepezil</mesh_term>
    <mesh_term>Galantamine</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/NCT01677754
org study id: BP28248
secondary id: 2012-000943-29
nct id: NCT01677754
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled
      study will evaluate the efficacy and safety of RO4602522 in participants with moderate
      severity Alzheimer's disease. Participants who are taking background therapy of
      acetylcholinesterase inhibitors (AChEI) alone or in combination with memantine for at least 4
      months before screening will be randomized to receive either one of two doses of RO4602522 or
      placebo for 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12
time frame: Baseline, Month 12
measure: Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (<=) 4 Points in ADAS-Cog-11
time frame: Baseline, Month 12
measure: Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12
time frame: Baseline, Month 12
measure: Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12
time frame: Baseline, Month 12
measure: Percentage of Participants With Worsening in BEHAVE-AD-FW Score
time frame: Baseline to Month 12
measure: Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months
time frame: Baseline, Month 12
measure: Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months
time frame: Baseline, Month 12
measure: Percentage of Participants With Worsening in ADCS-CGIC Score
time frame: Baseline to Month 12
measure: Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months
time frame: Baseline, Month 12
measure: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months
time frame: Baseline, Month 12
measure: Percentage of Participants with Adverse Events
time frame: Baseline up to 13 months
measure: Percentage of Participants with Change in Lens Opacity Grading
time frame: Baseline; Months 6, and 12
measure: Percentage of Participants with Abnormal Visual Acuity Test Results
time frame: Baseline, Months 6, and 12
measure: Change From Baseline in Michigan Neuropathy Screening Instrument Score
time frame: Baseline, Weeks 8, 18, 30, 44, 52, and at the last follow-up visit (12 weeks after last dose, up to 64 weeks)
measure: Percentage of Participants Receiving Concomitant Medications
time frame: Baseline to 13 Months
measure: Apparent Total Clearance of the Drug From Plasma After Administration of RO4602522
time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
measure: Apparent Volume of Distribution at Steady State after Administration of RO4602522
time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
measure: Area Under the Plasma Concentration-Time Curve of RO4602522
time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
measure: Maximum Plasma Concentration of RO4602522
time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.
arm group label: RO4602522 1 milligram (mg)
arm group type: Experimental
description: Participants will receive RO4602522 1 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.
arm group label: RO4602522 5 mg
arm group type: Experimental
description: Participants will receive RO4602522 5 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine.
intervention type: Drug
intervention name: RO4602522
description: Participants will receive RO4602522 orally once daily for 12 months.
arm group label: RO4602522 1 milligram (mg)
arm group label: RO4602522 5 mg
intervention type: Drug
intervention name: Placebo
description: Participants will receive placebo for RO4602522 orally once daily for 12 months.
arm group label: Placebo
intervention type: Drug
intervention name: Donepezil
description: Stable dose as background medication
arm group label: Placebo
arm group label: RO4602522 1 milligram (mg)
arm group label: RO4602522 5 mg
intervention type: Drug
intervention name: Memantine
description: Stable dose as background medication in combination with AChEIs
arm group label: Placebo
arm group label: RO4602522 1 milligram (mg)
arm group label: RO4602522 5 mg
intervention type: Drug
intervention name: Rivastigmine
description: Stable dose as background medication
arm group label: Placebo
arm group label: RO4602522 1 milligram (mg)
arm group label: RO4602522 5 mg
intervention type: Drug
intervention name: Galantamine
description: Stable dose as background medication
arm group label: Placebo
arm group label: RO4602522 1 milligram (mg)
arm group label: RO4602522 5 mg
criteria: 
gender: All
minimum age: 50 Years
maximum age: 90 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Australia
country: Canada
country: Czechia
country: France
country: Germany
country: Italy
country: Korea, Republic of
country: Poland
country: Spain
country: Sweden
country: United Kingdom
country: United States
country: Czech Republic
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Memantine
mesh term: Rivastigmine
mesh term: Donepezil
mesh term: Galantamine