<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/NCT04474405</url>
  </required_header>
  <id_info>
    <org_study_id>18F-AV-1451-A01</org_study_id>
    <nct_id>NCT04474405</nct_id>
  </id_info>
  <brief_title>Exploratory Evaluation of Flortaucipir Injection in Healthy Volunteers and Cognitively Impaired Subjects</brief_title>
  <official_title>An Exploratory Evaluation of the Tau Protein Binding Properties, Whole-Body Biodistribution and Safety of 18F-AV-1451 Injection in Healthy Volunteers and Cognitively Impaired Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Avid Radiopharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Avid Radiopharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This early phase 1 study explored the brain uptake, retention, and safety of flortaucipir and&#xD;
      obtained preliminary information regarding dosimetry of flortaucipir.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 16, 2013</start_date>
  <completion_date type="Actual">December 9, 2013</completion_date>
  <primary_completion_date type="Actual">December 9, 2013</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brain Flortaucipir Uptake</measure>
    <time_frame>80-100 minutes postdose</time_frame>
    <description>Brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVr), normalized to the entire cerebellum. A global cortical average volume of interest (VOI) is the average SUVr of the occipital cortex, parietal cortex, and temporal cortex. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Flortaucipir Whole Body Effective Dose</measure>
    <time_frame>injection to 6 hours postdose</time_frame>
    <description>Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam)</measure>
    <time_frame>at baseline</time_frame>
    <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on the Mini-Mental State Examination (MMSE). MMSE is a 30-point questionnaire that is used to measure cognitive impairment. 0 is the lowest score and 30 is the highest score, indicating normal cognitive function. Lower MMSE scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test)</measure>
    <time_frame>at baseline</time_frame>
    <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on Digit Symbol Substitution Test (DSST). The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function. Scores range from 0 to 133. Lower DSST scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale)</measure>
    <time_frame>at baseline</time_frame>
    <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on a Modified Alzheimer's Disease Assessment Scale (ADAS)-Cognitive subscale (including orientation, verbal memory, language, and praxis, minus the spoken language assessment). Scores on the modified scale can range from 0 to 65. Higher scores indicate worsening cognitive function. For this analysis, positive correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and negative correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Brain flortaucipir PET scan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receiving a brain PET scan after flortaucipir administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whole body flortaucipir PET scan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receiving a whole body PET scan after flortaucipir administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MRI and Amyloid Extension Cohort</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Flortaucipir F18</intervention_name>
    <description>IV injection, 370 MBq (10 mCi), single dose</description>
    <arm_group_label>Brain flortaucipir PET scan</arm_group_label>
    <arm_group_label>Whole body flortaucipir PET scan</arm_group_label>
    <other_name>18F-AV-1451</other_name>
    <other_name>[F-18]T807</other_name>
    <other_name>LY3191748</other_name>
    <other_name>Tauvid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Brain PET Scan</intervention_name>
    <description>positron emission tomography (PET) scan of the brain starting immediately after administration (60 minute dynamic imaging plus 4 frames x 5 minutes at approximately 80 minutes post-dose).</description>
    <arm_group_label>Brain flortaucipir PET scan</arm_group_label>
    <arm_group_label>MRI and Amyloid Extension Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Whole body PET scan</intervention_name>
    <description>positron emission tomography (PET) scan of the body from the vertex of the head to the thighs starting immediately following injection and repeated over 6 hours</description>
    <arm_group_label>Whole body flortaucipir PET scan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Florbetapir F 18</intervention_name>
    <description>IV injection, 370 MBq (10 mCi), single dose</description>
    <arm_group_label>Brain flortaucipir PET scan</arm_group_label>
    <arm_group_label>MRI and Amyloid Extension Cohort</arm_group_label>
    <other_name>Amyvid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Brain MRI</intervention_name>
    <description>Volume-based T1-weighted Magnetic Resonance Imaging (MRI) of the brain</description>
    <arm_group_label>Brain flortaucipir PET scan</arm_group_label>
    <arm_group_label>MRI and Amyloid Extension Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers had an Mini-Mental State Examination (MMSE) score of ≥ 29;&#xD;
&#xD;
          -  MCI due to Alzheimer's disease (AD) consistent with National Institute on Aging&#xD;
             (NIA)-Alzheimer's Association working group's on diagnostic guidelines for AD&#xD;
             (Alzheimer's Dementia 7:270-9, 2011)&#xD;
&#xD;
          -  Possible or probable AD: Met clinical criteria for possible or probable AD based on&#xD;
             the NIA-Alzheimer's Association working group's on diagnostic guidelines for AD&#xD;
             (Alzheimer's Dementia 7:263-9, 2011)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current clinically significant psychiatric disease.&#xD;
&#xD;
          -  Evidence of structural abnormalities such as major stroke or mass on MRI that would&#xD;
             have made a diagnosis of impairment due to AD unlikely or was likely to interfere with&#xD;
             interpretation of a PET scan on MRI.&#xD;
&#xD;
          -  Claustrophobic or otherwise unable to tolerate the imaging procedure.&#xD;
&#xD;
          -  Current clinically significant cardiovascular disease or clinically significant&#xD;
             abnormalities on screening electrocardiogram (including, but not limited to, corrected&#xD;
             QT interval &gt;450 msec).&#xD;
&#xD;
          -  Current clinically significant infectious disease, endocrine or metabolic disease,&#xD;
             pulmonary, renal or hepatic impairment, or cancer&#xD;
&#xD;
          -  History of alcohol abuse or substance abuse or dependence&#xD;
&#xD;
          -  Female subjects of childbearing potential who were not surgically sterile, not&#xD;
             refraining from sexual activity or not using reliable methods of contraception.&#xD;
&#xD;
          -  Required medications with a narrow therapeutic window&#xD;
&#xD;
          -  Received a non-study related radiopharmaceutical imaging or treatment procedure within&#xD;
             7 days prior to imaging session&#xD;
&#xD;
          -  Receiving any investigational medications or had participated in a trial with&#xD;
             investigational medications within the last 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Avid Radiopharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>WCCT Global, LLC</name>
      <address>
        <city>Cypress</city>
        <state>California</state>
        <zip>90630</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hoag Memorial Hospital Presbyterian</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92658</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <results_first_submitted>July 27, 2020</results_first_submitted>
  <results_first_submitted_qc>September 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 25, 2020</results_first_posted>
  <last_update_submitted>September 3, 2020</last_update_submitted>
  <last_update_submitted_qc>September 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 25, 2020</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>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment occurred between Aug and Dec 2013. Subjects in the MRI and Amyloid Extension cohort received flortaucipir brain PET scans in Study T807000 (NCT01733355)</recruitment_details>
      <pre_assignment_details>Subjects enrolled in the MRI/amyloid extension cohort were to be combined with the Brain PET subgroups for analysis per protocol. MRI allows previously-obtained flortaucipir scan and cognitive data to be combined with the PET scan results from the Brain PET subgroups for analysis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Brain PET Scan (AD Subjects)</title>
          <description>Alzheimer's disease (AD) subjects receiving a flortaucipir and florbetapir PET scan</description>
        </group>
        <group group_id="P2">
          <title>Brain PET (MCI Subjects)</title>
          <description>Mild cognitive impairment (MCI) subjects receiving a florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="P3">
          <title>Brain PET (YCN Subjects)</title>
          <description>Young cognitively normal (YCN) subjects receiving florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="P4">
          <title>Brain PET (OCN Subjects)</title>
          <description>Older cognitively normal (OCN) subjects receiving a florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="P5">
          <title>Whole Body PET Scan</title>
          <description>Subjects receiving a whole body PET scan after flortaucipir administration</description>
        </group>
        <group group_id="P6">
          <title>MRI and Amyloid Extension Cohort</title>
          <description>Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000. [n=3 AD, n=2 MCI, n=1 OCN]</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Flortaucipir PET Scan</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Florbetapir PET Scan</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="7"/>
              </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="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <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="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</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="3"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline demographics analysis includes subjects receiving a florbetapir or a flortaucipir PET scan in the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Brain PET Scan (AD Subjects)</title>
          <description>AD subjects receiving a flortaucipir and florbetapir PET scan</description>
        </group>
        <group group_id="B2">
          <title>Brain PET (MCI Subjects)</title>
          <description>Mild cognitive impairment (MCI) subjects receiving a florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="B3">
          <title>Brain PET (YCN Subjects)</title>
          <description>Young cognitively normal (YCN) subjects receiving florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="B4">
          <title>Brain PET (OCN Subjects)</title>
          <description>Older cognitively normal (OCN) subjects receiving a florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="B5">
          <title>Whole Body PET Scan</title>
          <description>Subjects receiving a whole body PET scan after flortaucipir administration</description>
        </group>
        <group group_id="B6">
          <title>MRI and Amyloid Extension Cohort</title>
          <description>Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000. [n=3 AD, n=2 MCI, n=1 OCN]</description>
        </group>
        <group group_id="B7">
          <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="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="4"/>
            <count group_id="B5" value="9"/>
            <count group_id="B6" value="4"/>
            <count group_id="B7" value="28"/>
          </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="68.0" spread="7.87"/>
                    <measurement group_id="B2" value="78.7" spread="2.89"/>
                    <measurement group_id="B3" value="27.5" spread="2.08"/>
                    <measurement group_id="B4" value="66.3" spread="0.50"/>
                    <measurement group_id="B5" value="56.3" spread="4.42"/>
                    <measurement group_id="B6" value="73.0" spread="13.09"/>
                    <measurement group_id="B7" value="60.1" spread="16.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</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="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" 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="4"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="8"/>
                  </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 group_id="B7" 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="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="18"/>
                  </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 group_id="B7" 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="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="9"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Brain Flortaucipir Uptake</title>
        <description>Brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVr), normalized to the entire cerebellum. A global cortical average volume of interest (VOI) is the average SUVr of the occipital cortex, parietal cortex, and temporal cortex. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.</description>
        <time_frame>80-100 minutes postdose</time_frame>
        <population>Includes quantitative flortaucipir PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans (n=3 AD, n=2 MCI, n=1 OCN) and received MRI in the present study permitting quantitative analysis per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Brain PET Scan (AD Subjects)</title>
            <description>AD subjects receiving a flortaucipir and florbetapir PET scan</description>
          </group>
          <group group_id="O2">
            <title>Brain PET (MCI Subjects)</title>
            <description>Mild cognitive impairment (MCI) subjects receiving a florbetapir and a flortaucipir PET scan</description>
          </group>
          <group group_id="O3">
            <title>Brain PET (YCN Subjects)</title>
            <description>Young cognitively normal (YCN) subjects receiving florbetapir and a flortaucipir PET scan</description>
          </group>
          <group group_id="O4">
            <title>Brain PET (OCN Subjects)</title>
            <description>Older cognitively normal (OCN) subjects receiving a florbetapir and a flortaucipir PET scan</description>
          </group>
        </group_list>
        <measure>
          <title>Brain Flortaucipir Uptake</title>
          <description>Brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVr), normalized to the entire cerebellum. A global cortical average volume of interest (VOI) is the average SUVr of the occipital cortex, parietal cortex, and temporal cortex. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.</description>
          <population>Includes quantitative flortaucipir PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans (n=3 AD, n=2 MCI, n=1 OCN) and received MRI in the present study permitting quantitative analysis per protocol.</population>
          <units>standardized uptake value ratio (SUVr)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.780" spread="0.857"/>
                    <measurement group_id="O2" value="1.317" spread="0.161"/>
                    <measurement group_id="O3" value="1.128" spread="0.047"/>
                    <measurement group_id="O4" value="1.107" spread="0.175"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Flortaucipir Whole Body Effective Dose</title>
        <description>Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model.</description>
        <time_frame>injection to 6 hours postdose</time_frame>
        <population>Includes only subjects from the whole body PET scan group (n=9)</population>
        <group_list>
          <group group_id="O1">
            <title>Whole Body Flortaucipir PET Scan</title>
            <description>Subjects receiving a whole body PET scan after flortaucipir administration</description>
          </group>
        </group_list>
        <measure>
          <title>Flortaucipir Whole Body Effective Dose</title>
          <description>Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model.</description>
          <population>Includes only subjects from the whole body PET scan group (n=9)</population>
          <units>mSv/MBq</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0241" spread="0.00160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam)</title>
        <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on the Mini-Mental State Examination (MMSE). MMSE is a 30-point questionnaire that is used to measure cognitive impairment. 0 is the lowest score and 30 is the highest score, indicating normal cognitive function. Lower MMSE scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
        <time_frame>at baseline</time_frame>
        <population>Includes quantitative flortaucipir brain PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans from a previous study (n=6) and received MRI in the present study permitting quantitation per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects/Brain PET</title>
            <description>Includes all AD, MCI, YCN, and OCN subjects enrolled in the study with flortaucipir Brain PET scans</description>
          </group>
        </group_list>
        <measure>
          <title>Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam)</title>
          <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on the Mini-Mental State Examination (MMSE). MMSE is a 30-point questionnaire that is used to measure cognitive impairment. 0 is the lowest score and 30 is the highest score, indicating normal cognitive function. Lower MMSE scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
          <population>Includes quantitative flortaucipir brain PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans from a previous study (n=6) and received MRI in the present study permitting quantitation per protocol.</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.404" lower_limit="-0.706" upper_limit="0.044"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test)</title>
        <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on Digit Symbol Substitution Test (DSST). The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function. Scores range from 0 to 133. Lower DSST scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
        <time_frame>at baseline</time_frame>
        <population>Includes quantitative flortaucipir PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans from a previous study n=6) and received MRI in the present study permitting quantitation per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects/Brain PET</title>
            <description>Includes all AD, MCI, YCN, and OCN subjects enrolled in the study with flortaucipir Brain PET scans</description>
          </group>
        </group_list>
        <measure>
          <title>Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test)</title>
          <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on Digit Symbol Substitution Test (DSST). The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function. Scores range from 0 to 133. Lower DSST scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
          <population>Includes quantitative flortaucipir PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans from a previous study n=6) and received MRI in the present study permitting quantitation per protocol.</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.273" lower_limit="-0.744" upper_limit="0.403"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale)</title>
        <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on a Modified Alzheimer's Disease Assessment Scale (ADAS)-Cognitive subscale (including orientation, verbal memory, language, and praxis, minus the spoken language assessment). Scores on the modified scale can range from 0 to 65. Higher scores indicate worsening cognitive function. For this analysis, positive correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and negative correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
        <time_frame>at baseline</time_frame>
        <population>Includes quantitative flortaucipir PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans from a previous study (n=6) and received MRI in the present study permitting quantitation per protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects/Brain PET</title>
            <description>Includes all AD, MCI, YCN, and OCN subjects enrolled in the study with flortaucipir Brain PET scans</description>
          </group>
        </group_list>
        <measure>
          <title>Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale)</title>
          <description>Spearman's correlations between flortaucipir SUVr and cognitive function as measured on a Modified Alzheimer's Disease Assessment Scale (ADAS)-Cognitive subscale (including orientation, verbal memory, language, and praxis, minus the spoken language assessment). Scores on the modified scale can range from 0 to 65. Higher scores indicate worsening cognitive function. For this analysis, positive correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and negative correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.</description>
          <population>Includes quantitative flortaucipir PET scan results from subjects with a flortaucipir scan in the present study (n=15), plus subjects consented in the MRI/Amyloid extension cohort who provided valid flortaucipir PET scans from a previous study (n=6) and received MRI in the present study permitting quantitation per protocol.</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.220" lower_limit="-0.447" upper_limit="0.719"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Flortaucipir Whole Body Effective Dose With Urine Radioactivity</title>
        <description>Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model and accounting for total integrated radioactivity excreted in the urine collected in Study A15 (NCT02336360)</description>
        <time_frame>injection to 6 hours postdose</time_frame>
        <population>Includes only subjects from the whole body PET scan group (n=9)</population>
        <group_list>
          <group group_id="O1">
            <title>Whole Body Flortaucipir PET Scan</title>
            <description>Subjects receiving a whole body PET scan after flortaucipir administration</description>
          </group>
        </group_list>
        <measure>
          <title>Flortaucipir Whole Body Effective Dose With Urine Radioactivity</title>
          <description>Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model and accounting for total integrated radioactivity excreted in the urine collected in Study A15 (NCT02336360)</description>
          <population>Includes only subjects from the whole body PET scan group (n=9)</population>
          <units>mSv/MBq</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0235" spread="0.0016"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>End of study for AE reporting was 48 hours after the last study drug administration.</time_frame>
      <desc>Adverse Events were defined as occurring or worsening after injection of dose, within 48 hours post injection of florbetapir or flortaucipir. AEs occurring after study drug administration, but outside that window were not recorded in the database, unless considered attributable to study drug injection. MRI/Amyloid extension cohort n=4 represents only those subjects receiving florbetapir PET scans.</desc>
      <group_list>
        <group group_id="E1">
          <title>Brain PET Scan (AD Subjects)</title>
          <description>AD subjects receiving a flortaucipir and florbetapir PET scan</description>
        </group>
        <group group_id="E2">
          <title>Brain PET (MCI Subjects)</title>
          <description>Mild cognitive impairment (MCI) subjects receiving a florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="E3">
          <title>Brain PET (YCN Subjects)</title>
          <description>Young cognitively normal (YCN) subjects receiving florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="E4">
          <title>Brain PET (OCN Subjects)</title>
          <description>Older cognitively normal (OCN) subjects receiving a florbetapir and a flortaucipir PET scan</description>
        </group>
        <group group_id="E5">
          <title>Whole Body PET Scan</title>
          <description>Subjects receiving a whole body PET scan after flortaucipir administration</description>
        </group>
        <group group_id="E6">
          <title>MRI and Amyloid Extension Cohort</title>
          <description>Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000</description>
        </group>
      </group_list>
      <serious_events>
        <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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0.5</frequency_threshold>
        <default_vocab>MedDRA (16.1)</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="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>musculoskeletal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Director</name_or_title>
      <organization>Avid Radiopharmaceuticals, Inc.</organization>
      <phone>215-298-0700</phone>
      <email>clinicaloperations@avidrp.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/NCT04474405
org study id: 18F-AV-1451-A01
nct id: NCT04474405
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This early phase 1 study explored the brain uptake, retention, and safety of flortaucipir and
      obtained preliminary information regarding dosimetry of flortaucipir.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Brain Flortaucipir Uptake
time frame: 80-100 minutes postdose
description: Brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVr), normalized to the entire cerebellum. A global cortical average volume of interest (VOI) is the average SUVr of the occipital cortex, parietal cortex, and temporal cortex. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
measure: Flortaucipir Whole Body Effective Dose
time frame: injection to 6 hours postdose
description: Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model.
measure: Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam)
time frame: at baseline
description: Spearman's correlations between flortaucipir SUVr and cognitive function as measured on the Mini-Mental State Examination (MMSE). MMSE is a 30-point questionnaire that is used to measure cognitive impairment. 0 is the lowest score and 30 is the highest score, indicating normal cognitive function. Lower MMSE scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.
measure: Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test)
time frame: at baseline
description: Spearman's correlations between flortaucipir SUVr and cognitive function as measured on Digit Symbol Substitution Test (DSST). The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function. Scores range from 0 to 133. Lower DSST scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.
measure: Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale)
time frame: at baseline
description: Spearman's correlations between flortaucipir SUVr and cognitive function as measured on a Modified Alzheimer's Disease Assessment Scale (ADAS)-Cognitive subscale (including orientation, verbal memory, language, and praxis, minus the spoken language assessment). Scores on the modified scale can range from 0 to 65. Higher scores indicate worsening cognitive function. For this analysis, positive correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and negative correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.
arm group label: Brain flortaucipir PET scan
arm group type: Experimental
description: Subjects receiving a brain PET scan after flortaucipir administration
arm group label: Whole body flortaucipir PET scan
arm group type: Experimental
description: Subjects receiving a whole body PET scan after flortaucipir administration
arm group label: MRI and Amyloid Extension Cohort
arm group type: Other
description: Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355)
intervention type: Drug
intervention name: Flortaucipir F18
description: IV injection, 370 MBq (10 mCi), single dose
arm group label: Brain flortaucipir PET scan
arm group label: Whole body flortaucipir PET scan
other name: 18F-AV-1451
other name: [F-18]T807
other name: LY3191748
other name: Tauvid
intervention type: Procedure
intervention name: Brain PET Scan
description: positron emission tomography (PET) scan of the brain starting immediately after administration (60 minute dynamic imaging plus 4 frames x 5 minutes at approximately 80 minutes post-dose).
arm group label: Brain flortaucipir PET scan
arm group label: MRI and Amyloid Extension Cohort
intervention type: Procedure
intervention name: Whole body PET scan
description: positron emission tomography (PET) scan of the body from the vertex of the head to the thighs starting immediately following injection and repeated over 6 hours
arm group label: Whole body flortaucipir PET scan
intervention type: Drug
intervention name: Florbetapir F 18
description: IV injection, 370 MBq (10 mCi), single dose
arm group label: Brain flortaucipir PET scan
arm group label: MRI and Amyloid Extension Cohort
other name: Amyvid
intervention type: Procedure
intervention name: Brain MRI
description: Volume-based T1-weighted Magnetic Resonance Imaging (MRI) of the brain
arm group label: Brain flortaucipir PET scan
arm group label: MRI and Amyloid Extension Cohort
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Director
role: Study Director
affiliation: Avid Radiopharmaceuticals, Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 