<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/NCT02240693</url>
  </required_header>
  <id_info>
    <org_study_id>1289.5</org_study_id>
    <secondary_id>2013-005031-24</secondary_id>
    <nct_id>NCT02240693</nct_id>
  </id_info>
  <brief_title>Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo</brief_title>
  <official_title>A Multi-centre, Double-blind, Parallel-group, Randomized Controlled Study to Investigate the Efficacy, Safety and Tolerability of Orally Administered BI 409306 During a 12-week Treatment Period Compared to Placebo in Patients With Alzheimer Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The study is designed to compare the effects of 4 different doses of orally administered BI&#xD;
      409306 to placebo in patients with Alzheimers Disease&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2015</start_date>
  <completion_date type="Actual">October 9, 2017</completion_date>
  <primary_completion_date type="Actual">September 18, 2017</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 Neuropsychological Test Battery in Total Z-score After 12-week Treatment.</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Twin Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) Total Score After 12-week Treatment</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) is a rating scale used to assess basic and instrumental activities of daily living. In the full version of the scale, 23 items are rated by the investigator using information supplied by the caregiver.&#xD;
Each item has a score range varying from 0-3 to 0-5. The sum score can range from 0 to 78. Higher scores indicate better function.&#xD;
Least Squares Mean is actually an adjusted mean change from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>The CDR-SB is obtained through semi-structured interviews of patients and informants, and cognitive functioning was rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care.&#xD;
Each domain was rated on a 5-point scale of functioning as follows: 0-no impairment; 0.5-questionable impairment; 1-mild impairment; 2-moderate impairment and 3-severe impairment. Only personal care was scored on a 4-point scale without a 0.5 rating available. The higher the score, the greater the severity of dementia. Least Squares Mean is actually an adjusted mean change from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog11) is an 11-item cognitive subscale that objectively measures memory, language, orientation, and praxis with a total score range of 0 to 70. The greater the dysfunction, the greater the score. Least Squares Mean is actually an adjusted mean change from baseline.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">128</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>BI 409306 dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 409306 dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 409306 dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 409306 dose 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 409306</intervention_name>
    <arm_group_label>BI 409306 dose 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>BI 409306 dose 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 409306</intervention_name>
    <arm_group_label>BI 409306 dose 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>BI 409306 dose 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 409306</intervention_name>
    <arm_group_label>BI 409306 dose 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 409306</intervention_name>
    <arm_group_label>BI 409306 dose 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>BI 409306 dose 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>BI 409306 dose 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Male and female patients with an age of at least 55 years&#xD;
&#xD;
          -  Body weight not lower than 50 kgs&#xD;
&#xD;
          -  Patients with a confirmed diagnosis of prodromal Alzheimer's Dementia (AD) on&#xD;
             neuropsychological testing defined as:&#xD;
&#xD;
        Mini-Mental State Examination (MMSE) score: greater or equal 24 and a global Clinical&#xD;
        Dementia Rating (CDR)-score of 0 or 0.5 and&#xD;
&#xD;
        Free and Cued Selective Recall Reminding Test (FCSRT) score:&#xD;
&#xD;
        free recall test: lower or equal 20 (out of 48) and total recall test: lower or equal 42&#xD;
        (out of 48)&#xD;
&#xD;
        Patients who do not reach the required score in FCSRT will additionally perform the&#xD;
        Wechsler Memory Visual Paired Associates test. If the Wechsler Memory Visual Paired&#xD;
        Associates test shows a cognitive deficit worse than 1 standard deviation to the mean&#xD;
        (compared to the reference values of age and educational norms for inclusion), then the&#xD;
        patients can be considered to be eligible for the study.&#xD;
&#xD;
          -  Confirmation of abnormal markers of AD pathology either via a), or alternatively b)&#xD;
             mentioned below:&#xD;
&#xD;
               1. Presence in cerebrospinal fluid of (samples taken within past 4 months may be&#xD;
                  eligible,:&#xD;
&#xD;
                  low Aß1-42 concentrations (&lt; 640 pg/mL) and increased total tau concentrations (&gt;&#xD;
                  375 pg/ml), or / and low Aß1-42 concentrations (&lt; 640 pg/mL) and increased&#xD;
                  phospho-tau concentrations (&gt; 52 pg/mL in cerebrospinal fluid), or&#xD;
&#xD;
               2. Abnormal amyloid deposition in a cerebral Positron Emission Tomography (PET)&#xD;
                  scan. Scans performed in the past according to the recommendation in the protocol&#xD;
                  are acceptable&#xD;
&#xD;
          -  Patients who have not received prescribed drugs for treatment of AD (including acetyl&#xD;
             cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, phenserine)&#xD;
             and Memantine within three months prior to screening&#xD;
&#xD;
          -  Patients must have at least 6 years of formal education and fluency in the test&#xD;
             language as verbally confirmed by the patient and documented by the study&#xD;
             investigator.&#xD;
&#xD;
          -  Patients must have given written informed consent in accordance with Good Clinical&#xD;
             Practice (GCP) and local legislation prior to any study procedures. All patients must&#xD;
             be able to give informed consent personally and have capacity for such consent. An&#xD;
             informed consent given by a legal representative will not be accepted.&#xD;
&#xD;
          -  Patients must have a reliable study partner (per investigator judgement, for instance&#xD;
             a family member, partner, guardian etc.)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Mild cognitive impairment with any etiology other than prodromal AD (for example:&#xD;
             neurosyphilis, craniocerebral trauma, small vessel disease) based on clinical data&#xD;
             and/or current laboratory findings and/or a pre-existing MRI or CT of the brain (CCT).&#xD;
             If previous cranial imaging is not available or older than 12 months prior to&#xD;
             screening then a CCT or MRI needs to be performed at screening&#xD;
&#xD;
          -  Substantial concomitant cerebrovascular disease (defined by a history of a stroke /&#xD;
             intracranial haemorrhagia) temporally related to the onset of worsening of cognitive&#xD;
             impairment per investigator judgement&#xD;
&#xD;
          -  Medical history of cancer (except for basal cell carcinoma) and/or treatment for&#xD;
             cancer within the last 5 years&#xD;
&#xD;
          -  Medical history or diagnosis of any of symptomatic and unstable/uncontrolled&#xD;
             conditions per investigator judgement&#xD;
&#xD;
          -  Severe renal impairment defined with a glomerular filtration rate (GFR) &lt;&#xD;
             30ml/min/1.73m2 in the screening central lab report&#xD;
&#xD;
          -  Any other psychiatric disorders such as schizophrenia, or mental retardation&#xD;
&#xD;
          -  Any suicidal actions in the past 2 years (per investigator judgement i.e. actual&#xD;
             attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)&#xD;
&#xD;
          -  Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale&#xD;
             (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without&#xD;
             specific plan, or active suicidal thought with plan and intent)&#xD;
&#xD;
          -  Previous participation in investigational drug studies of mild cognitive impairment&#xD;
             within three months prior to screening. Having received active treatment in any other&#xD;
             study targeting disease modification like Aß immunization and tau therapies. Previous&#xD;
             participation in studies with non-prescription medications, vitamins or other&#xD;
             nutritional formulations is allowed.&#xD;
&#xD;
          -  Significant history of drug dependence or abuse (including alcohol, as defined in&#xD;
             Diagnostic and Statistical Manual of Mental Disorders [DSM-V] or in the opinion of the&#xD;
             investigator) within the last two years, or a positive urine drug screen for cocaine,&#xD;
             heroin, or marijuana.&#xD;
&#xD;
          -  Known history of HIV infection&#xD;
&#xD;
          -  Any planned surgeries requiring general anaesthesia, or hospitalisation for more than&#xD;
             1 day during the study period&#xD;
&#xD;
          -  Pre-menopausal women (last menstruation &lt;= 1 year prior to informed consent) who are&#xD;
             nursing or pregnant or are of child-bearing potential and are not practicing an&#xD;
             acceptable method of birth control&#xD;
&#xD;
          -  For male patients: Men who are able to father a child, unwilling to be abstinent or to&#xD;
             use an adequate form of effective contraception for the duration of study&#xD;
             participation and for at least 28 days after treatment has ended.&#xD;
&#xD;
          -  Use of any investigational drug or procedure for other indications within 3 months or&#xD;
             6 half-lives (whichever is longer) prior to randomization.&#xD;
&#xD;
          -  Intake of the following medications within 3 months prior to randomization and&#xD;
             intended to be initiated during the duration of the trial:&#xD;
&#xD;
               1. tricyclic antidepressants,&#xD;
&#xD;
               2. antidepressants that are monoamine oxidase inhibitors,&#xD;
&#xD;
               3. neuroleptics with moderate or greater anticholinergic potency (e.g.&#xD;
                  chlorpromazine, fluphenazine, loxapine, perphenazine, thioridazine),&#xD;
&#xD;
               4. anticholinergic medications&#xD;
&#xD;
        The following drugs may be given as needed if the total daily dose was stable 8 weeks prior&#xD;
        to randomisation and is expected to be for the duration of the trial:&#xD;
&#xD;
          1. neuroleptics listed in the protocol&#xD;
&#xD;
          2. benzodiazepines and sedatives listed in the protocol&#xD;
&#xD;
               -  Clinically significant uncompensated hearing loss in the judgment of the&#xD;
                  investigator. Use of hearing aids is allowed.&#xD;
&#xD;
               -  Known hypersensitivity to the drug product excipients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Orange County Neuropsychiatric Research Center LLC</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Neuroscience Research</name>
      <address>
        <city>Sherman Oaks</city>
        <state>California</state>
        <zip>91403</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>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>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>ANI Neurology, PLLC, dba Alzheimer's Memory Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28270</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulsa Clinical Research, LLC</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landeskrankenhaus Hall, Abt.f. Psychatrie &amp; Psychotherapie A</name>
      <address>
        <city>Hall in Tirol</city>
        <zip>6060</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Private Practice for Psychiatry and Neurology</name>
      <address>
        <city>Wien</city>
        <zip>1130</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brussels-UNIV Brugmann -Horta</name>
      <address>
        <city>Brussel</city>
        <zip>1020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Jubilee Hospital</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <zip>V8R 1J8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>True North Clinical Research Halifax, Inc.</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3S 1M7</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>B4B 4K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Memory Program</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M3B 2S7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut universitaire de geriatrie Sherbrooke</name>
      <address>
        <city>Quebec</city>
        <zip>J1J 3H5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HOP Pierre Wertheimer</name>
      <address>
        <city>Bron</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HOP Gui de Chauliac</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HOP Nord Laënnec</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HOP La Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HOP Jean Bernard, Géria, Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. med. Volker Schumann</name>
      <address>
        <city>Berlin</city>
        <zip>10245</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>emovis GmbH</name>
      <address>
        <city>Berlin</city>
        <zip>10629</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AFL Arzneimittelforschung Leipzig GmbH</name>
      <address>
        <city>Leipzig</city>
        <zip>04107</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zentralinstitut für seelische Gesundheit</name>
      <address>
        <city>Mannheim</city>
        <zip>68159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurologie und Psychiatrie / Psychotherapie</name>
      <address>
        <city>Westerstede</city>
        <zip>26655</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osp. S. Giovanni di Dio</name>
      <address>
        <city>Firenze</city>
        <zip>50143</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Gemelli</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Research Center</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081 GN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Podlassian Center of Psychogeriatry, Bialystok</name>
      <address>
        <city>Bialystok</city>
        <zip>15-732</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Non-Public Outpat. Clinic &quot;Dom Sue Ryder&quot;, PALLMED Sp. z o.o</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-796</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Non-Public Outpatient Clinic &quot;Synapsa&quot; Pawel Polrola, Kielce</name>
      <address>
        <city>Kielce</city>
        <zip>25-103</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center Biomed</name>
      <address>
        <city>Kielce</city>
        <zip>25-411</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Non-Public Outpatient Clinic Neuro-Kard Ilkowski &amp; Partners</name>
      <address>
        <city>Poznan</city>
        <zip>61-853</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Senior</name>
      <address>
        <city>Sopot</city>
        <zip>81-855</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EUROMEDIS Sp. z o.o., Szczecin</name>
      <address>
        <city>Szczecin</city>
        <zip>70-111</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reg. Specialist Hospital Wroclaw, Research &amp; Develop. Center</name>
      <address>
        <city>Wroclaw</city>
        <zip>51-124</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Fernando Fonseca, EPE</name>
      <address>
        <city>Amadora</city>
        <zip>2700-276</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUC - Centro Hospitalar e Universitário de Coimbra, EPE</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHLO, EPE - Hospital Egas Moniz</name>
      <address>
        <city>Lisboa</city>
        <zip>1349-019</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHLN, EPE - Hospital de Santa Maria</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundación Alcorcón</name>
      <address>
        <city>Alcorcon (Madrid)</city>
        <zip>28922</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Arrixaca</name>
      <address>
        <city>El Palmar (murcia)</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari General de Catalunya</name>
      <address>
        <city>Sant Cugat del Vallès</city>
        <zip>08190</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Mútua Terrassa</name>
      <address>
        <city>Terrasa (Barcelona)</city>
        <zip>08221</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal United Hospital</name>
      <address>
        <city>Bath</city>
        <zip>BA1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <zip>PL21 9AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Re-Cognition Health</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8BT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <results_first_submitted>September 11, 2018</results_first_submitted>
  <results_first_submitted_qc>October 31, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 28, 2018</results_first_posted>
  <last_update_submitted>October 31, 2018</last_update_submitted>
  <last_update_submitted_qc>October 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</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>BI 409306</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT02240693/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT02240693/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A multi-centre, double-blind, parallel-group, randomized controlled study to investigate the efficacy, safety and tolerability of orally administered BI 409306 during a 12-week treatment period compared to placebo in patients with Alzheimer's Disease</recruitment_details>
      <pre_assignment_details>For this trial, patients were randomised at 36 sites in 11 countries. Following an initial Screening Visit and a single blinded 2-week placebo run-in period, patients who qualified according to the in- and exclusion criteria were randomised to one of the five treatment groups</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
          <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="P2">
          <title>BI 409306 25 mg QD</title>
          <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="P3">
          <title>BI 409306 50 mg QD</title>
          <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="P4">
          <title>BI 409306 25 mg Twice Daily (BID)</title>
          <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
        </group>
        <group group_id="P5">
          <title>Placebo Matching BI 409306</title>
          <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="21"/>
                <participants group_id="P4" count="21"/>
                <participants group_id="P5" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="17"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set:&#xD;
The treated set (TS) included all patients who were randomised and treated with at least one dose of trial medication.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
          <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="B2">
          <title>BI 409306 25 mg QD</title>
          <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="B3">
          <title>BI 409306 50 mg QD</title>
          <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="B4">
          <title>BI 409306 25 mg Twice Daily (BID)</title>
          <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
        </group>
        <group group_id="B5">
          <title>Placebo Matching BI 409306</title>
          <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
            <count group_id="B2" value="21"/>
            <count group_id="B3" value="21"/>
            <count group_id="B4" value="21"/>
            <count group_id="B5" value="43"/>
            <count group_id="B6" value="128"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72.3" spread="5.4"/>
                    <measurement group_id="B2" value="74.1" spread="8.1"/>
                    <measurement group_id="B3" value="73.3" spread="5.1"/>
                    <measurement group_id="B4" value="71.9" spread="6.0"/>
                    <measurement group_id="B5" value="72.2" spread="6.5"/>
                    <measurement group_id="B6" value="72.7" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="28"/>
                    <measurement group_id="B6" value="71"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="15"/>
                    <measurement group_id="B6" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>Race data is presented below; Ethnicity was not reported in this trial</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="43"/>
                    <measurement group_id="B6" value="128"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Neuropsychological Test Battery (NTB) Total</title>
          <description>Baseline cognitive assessment data- NTB total z-score. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Higher values indicate a better Outcome</description>
          <units>z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.07" spread="0.70"/>
                    <measurement group_id="B2" value="0.02" spread="0.75"/>
                    <measurement group_id="B3" value="-0.02" spread="0.72"/>
                    <measurement group_id="B4" value="-0.02" spread="0.61"/>
                    <measurement group_id="B5" value="-0.03" spread="0.63"/>
                    <measurement group_id="B6" value="-0.00" spread="0.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.</title>
        <description>Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <population>The full analysis set (FAS) included all randomised patients who were treated with at least one dose of trial medication and had a baseline and at least one post-baseline on-treatment efficacy assessment. Observed cases (OC)</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
            <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BI 409306 25 mg QD</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>BI 409306 50 mg QD</title>
            <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>BI 409306 25 mg Twice Daily (BID)</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Pooled BI 409306</title>
            <description>Patients were administered orally a tablet of BI 409306 (10 mg, 25 mg, 50 mg once daily and 25 mg twice daily)for 12 weeks.</description>
          </group>
          <group group_id="O6">
            <title>Placebo Matching BI 409306</title>
            <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.</title>
          <description>Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline</description>
          <population>The full analysis set (FAS) included all randomised patients who were treated with at least one dose of trial medication and had a baseline and at least one post-baseline on-treatment efficacy assessment. Observed cases (OC)</population>
          <units>z-score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="73"/>
                <count group_id="O6" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.35" spread="0.061"/>
                    <measurement group_id="O2" value="0.20" spread="0.063"/>
                    <measurement group_id="O3" value="0.26" spread="0.065"/>
                    <measurement group_id="O4" value="0.32" spread="0.064"/>
                    <measurement group_id="O5" value="0.29" spread="0.031"/>
                    <measurement group_id="O6" value="0.27" spread="0.043"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.3236</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.07</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.075</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.074</ci_lower_limit>
            <ci_upper_limit>0.223</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.3694</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.07</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.076</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.220</ci_lower_limit>
            <ci_upper_limit>0.082</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.8374</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.02</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.078</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.171</ci_lower_limit>
            <ci_upper_limit>0.139</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.5484</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.05</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.077</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.106</ci_lower_limit>
            <ci_upper_limit>0.199</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.7905</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.01</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.054</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.092</ci_lower_limit>
            <ci_upper_limit>0.121</ci_upper_limit>
            <estimate_desc>Mean difference (Pooled BI 409306 minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) Total Score After 12-week Treatment</title>
        <description>Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) is a rating scale used to assess basic and instrumental activities of daily living. In the full version of the scale, 23 items are rated by the investigator using information supplied by the caregiver.&#xD;
Each item has a score range varying from 0-3 to 0-5. The sum score can range from 0 to 78. Higher scores indicate better function.&#xD;
Least Squares Mean is actually an adjusted mean change from baseline.</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <population>FAS- Observed cases</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
            <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BI 409306 25 mg QD</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>BI 409306 50 mg QD</title>
            <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>BI 409306 25 mg Twice Daily (BID)</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Placebo Matching BI 409306</title>
            <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) Total Score After 12-week Treatment</title>
          <description>Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) is a rating scale used to assess basic and instrumental activities of daily living. In the full version of the scale, 23 items are rated by the investigator using information supplied by the caregiver.&#xD;
Each item has a score range varying from 0-3 to 0-5. The sum score can range from 0 to 78. Higher scores indicate better function.&#xD;
Least Squares Mean is actually an adjusted mean change from baseline.</description>
          <population>FAS- Observed cases</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="20"/>
                <count group_id="O4" value="17"/>
                <count group_id="O5" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24" spread="0.896"/>
                    <measurement group_id="O2" value="1.79" spread="0.921"/>
                    <measurement group_id="O3" value="-0.10" spread="0.875"/>
                    <measurement group_id="O4" value="0.80" spread="0.947"/>
                    <measurement group_id="O5" value="0.38" spread="0.642"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.8973</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.14</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.102</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.33</ci_lower_limit>
            <ci_upper_limit>2.04</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.2141</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.40</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.122</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.82</ci_lower_limit>
            <ci_upper_limit>3.63</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.6553</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.49</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.085</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.64</ci_lower_limit>
            <ci_upper_limit>1.67</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.7166</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.42</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.144</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.85</ci_lower_limit>
            <ci_upper_limit>2.69</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment</title>
        <description>The CDR-SB is obtained through semi-structured interviews of patients and informants, and cognitive functioning was rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care.&#xD;
Each domain was rated on a 5-point scale of functioning as follows: 0-no impairment; 0.5-questionable impairment; 1-mild impairment; 2-moderate impairment and 3-severe impairment. Only personal care was scored on a 4-point scale without a 0.5 rating available. The higher the score, the greater the severity of dementia. Least Squares Mean is actually an adjusted mean change from baseline.</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <population>FAS- Observed cases</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
            <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BI 409306 25 mg QD</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>BI 409306 50 mg QD</title>
            <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>BI 409306 25 mg Twice Daily (BID)</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Placebo Matching BI 409306</title>
            <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment</title>
          <description>The CDR-SB is obtained through semi-structured interviews of patients and informants, and cognitive functioning was rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care.&#xD;
Each domain was rated on a 5-point scale of functioning as follows: 0-no impairment; 0.5-questionable impairment; 1-mild impairment; 2-moderate impairment and 3-severe impairment. Only personal care was scored on a 4-point scale without a 0.5 rating available. The higher the score, the greater the severity of dementia. Least Squares Mean is actually an adjusted mean change from baseline.</description>
          <population>FAS- Observed cases</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="18"/>
                <count group_id="O5" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.19"/>
                    <measurement group_id="O2" value="0.4" spread="0.20"/>
                    <measurement group_id="O3" value="-0.1" spread="0.22"/>
                    <measurement group_id="O4" value="0.1" spread="0.21"/>
                    <measurement group_id="O5" value="0.1" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9491</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.24</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.49</ci_lower_limit>
            <ci_upper_limit>0.46</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1699</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.25</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.15</ci_lower_limit>
            <ci_upper_limit>0.84</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4948</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.26</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.69</ci_lower_limit>
            <ci_upper_limit>0.33</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7548</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.25</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.42</ci_lower_limit>
            <ci_upper_limit>0.58</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment</title>
        <description>Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog11) is an 11-item cognitive subscale that objectively measures memory, language, orientation, and praxis with a total score range of 0 to 70. The greater the dysfunction, the greater the score. Least Squares Mean is actually an adjusted mean change from baseline.</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <population>FAS- Observed cases</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
            <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BI 409306 25 mg QD</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>BI 409306 50 mg QD</title>
            <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>BI 409306 25 mg Twice Daily (BID)</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Placebo Matching BI 409306</title>
            <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment</title>
          <description>Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog11) is an 11-item cognitive subscale that objectively measures memory, language, orientation, and praxis with a total score range of 0 to 70. The greater the dysfunction, the greater the score. Least Squares Mean is actually an adjusted mean change from baseline.</description>
          <population>FAS- Observed cases</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="19"/>
                <count group_id="O5" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.98" spread="0.885"/>
                    <measurement group_id="O2" value="0.62" spread="0.935"/>
                    <measurement group_id="O3" value="0.12" spread="0.875"/>
                    <measurement group_id="O4" value="-1.27" spread="0.875"/>
                    <measurement group_id="O5" value="1.24" spread="0.619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.8137</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.26</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.081</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.40</ci_lower_limit>
            <ci_upper_limit>1.89</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.5801</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.62</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.120</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.84</ci_lower_limit>
            <ci_upper_limit>1.60</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.2978</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.12</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.072</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.25</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.</non_inferiority_desc>
            <p_value>0.0209</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.51</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.072</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.64</ci_lower_limit>
            <ci_upper_limit>-0.39</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Twin Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)</title>
        <description>Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <population>FAS observed cases for pooled groups of these twin trials</population>
        <group_list>
          <group group_id="O1">
            <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
            <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BI 409306 25 mg QD</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>BI 409306 50 mg QD</title>
            <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>BI 409306 25 mg Twice Daily (BID)</title>
            <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Pooled BI 409306</title>
            <description>Patients were administered orally a tablet of BI 409306 (10 mg, 25 mg, 50 mg once daily and 25 mg twice daily)for 12 weeks.</description>
          </group>
          <group group_id="O6">
            <title>Placebo Matching BI 409306</title>
            <description>Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Twin Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)</title>
          <description>Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline</description>
          <population>FAS observed cases for pooled groups of these twin trials</population>
          <units>z-score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="67"/>
                <count group_id="O2" value="63"/>
                <count group_id="O3" value="67"/>
                <count group_id="O4" value="63"/>
                <count group_id="O5" value="260"/>
                <count group_id="O6" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" spread="0.046"/>
                    <measurement group_id="O2" value="0.19" spread="0.048"/>
                    <measurement group_id="O3" value="0.19" spread="0.046"/>
                    <measurement group_id="O4" value="0.10" spread="0.047"/>
                    <measurement group_id="O5" value="0.17" spread="0.025"/>
                    <measurement group_id="O6" value="0.19" spread="0.035"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.&#xD;
The study identifier is also a categorical covariate for the twin studies analyses.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.8694</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.01</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.056</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.101</ci_lower_limit>
            <ci_upper_limit>0.120</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.&#xD;
The study identifier is also a categorical covariate for the twin studies analyses.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.9512</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.00</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.057</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.116</ci_lower_limit>
            <ci_upper_limit>0.109</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.&#xD;
The study identifier is also a categorical covariate for the twin studies analyses.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.9321</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.00</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.056</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.105</ci_lower_limit>
            <ci_upper_limit>0.115</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.&#xD;
The study identifier is also a categorical covariate for the twin studies analyses.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.1288</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.09</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.057</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.199</ci_lower_limit>
            <ci_upper_limit>0.025</ci_upper_limit>
            <estimate_desc>Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction. The study identifier is also a categorical covariate for the twin studies analyses.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.</non_inferiority_desc>
            <p_value>0.6492</p_value>
            <p_value_desc>p-value was nominal and not adjusted.</p_value_desc>
            <method>Mixed Model Repeated Measurement (MMRM)</method>
            <method_desc>Kenward-Roger was used to model degrees of freedom.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.02</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.041</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.098</ci_lower_limit>
            <ci_upper_limit>0.061</ci_upper_limit>
            <estimate_desc>Mean difference (Pooled BI 409306 minus Placebo matching BI 409306)</estimate_desc>
            <other_analysis_desc>The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study medication until 7 days after last administration of BI 409306, up to 16 weeks.</time_frame>
      <desc>The treated set (TS) used (all patients who were randomised and treated with at least one dose of trial medication.) for safety assessment.</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 409306 10 Milligram (mg) Once Daily (QD)</title>
          <description>Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="E2">
          <title>BI 409306 25 mg QD</title>
          <description>Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="E3">
          <title>BI 409306 50 mg QD</title>
          <description>Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.</description>
        </group>
        <group group_id="E4">
          <title>BI 409306 25 mg Twice Daily (BID)</title>
          <description>Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.</description>
        </group>
        <group group_id="E5">
          <title>Placebo Matching BI 409306</title>
          <description>Patients were administered orally tablet of Placebo matching BI 409306 once daily for 12 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim, Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02240693
org study id: 1289.5
secondary id: 2013-005031-24
nct id: NCT02240693
lead sponsor: 
The study is designed to compare the effects of 4 different doses of orally administered BI
      409306 to placebo in patients with Alzheimers Disease
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.
time frame: Baseline and 12 weeks
description: Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline
measure: Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Twin Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)
time frame: Baseline and 12 weeks
description: Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline
measure: Change From Baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) Total Score After 12-week Treatment
time frame: Baseline and 12 weeks
description: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) is a rating scale used to assess basic and instrumental activities of daily living. In the full version of the scale, 23 items are rated by the investigator using information supplied by the caregiver.
Each item has a score range varying from 0-3 to 0-5. The sum score can range from 0 to 78. Higher scores indicate better function.
Least Squares Mean is actually an adjusted mean change from baseline.
measure: Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment
time frame: Baseline and 12 weeks
description: The CDR-SB is obtained through semi-structured interviews of patients and informants, and cognitive functioning was rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care.
Each domain was rated on a 5-point scale of functioning as follows: 0-no impairment; 0.5-questionable impairment; 1-mild impairment; 2-moderate impairment and 3-severe impairment. Only personal care was scored on a 4-point scale without a 0.5 rating available. The higher the score, the greater the severity of dementia. Least Squares Mean is actually an adjusted mean change from baseline.
measure: Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment
time frame: Baseline and 12 weeks
description: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog11) is an 11-item cognitive subscale that objectively measures memory, language, orientation, and praxis with a total score range of 0 to 70. The greater the dysfunction, the greater the score. Least Squares Mean is actually an adjusted mean change from baseline.
arm group label: BI 409306 dose 1
arm group type: Experimental
arm group label: BI 409306 dose 2
arm group type: Experimental
arm group label: BI 409306 dose 3
arm group type: Experimental
arm group label: BI 409306 dose 4
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 409306
arm group label: BI 409306 dose 1
intervention type: Drug
intervention name: Placebo
arm group label: BI 409306 dose 2
intervention type: Drug
intervention name: BI 409306
arm group label: BI 409306 dose 2
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Placebo
arm group label: BI 409306 dose 1
intervention type: Drug
intervention name: BI 409306
arm group label: BI 409306 dose 3
intervention type: Drug
intervention name: BI 409306
arm group label: BI 409306 dose 4
intervention type: Drug
intervention name: Placebo
arm group label: BI 409306 dose 3
intervention type: Drug
intervention name: Placebo
arm group label: BI 409306 dose 4
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
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country: Austria
country: Belgium
country: Canada
country: France
country: Germany
country: Italy
country: Netherlands
country: Poland
country: Portugal
country: Spain
country: United Kingdom
country: United States
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: BI 409306
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 