<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/NCT01667367</url>
  </required_header>
  <id_info>
    <org_study_id>BP25611</org_study_id>
    <secondary_id>2012-001301-24</secondary_id>
    <nct_id>NCT01667367</nct_id>
  </id_info>
  <brief_title>A Molecular and Functional Brain Imaging Study in Individuals With Down Syndrome and Healthy Controls Following Single Dose RG1662</brief_title>
  <official_title>A Single-center, Single Blind Molecular and Functional Imaging Study to Assess GABAAalpha5 Receptor Expression, Occupancy and Functional Connectivity in the Brains of Individuals With Down Syndrome and Healthy Controls Following a Single Oral Administration of RG1662 or Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This single-center, single-blind, placebo-controlled, parallel-group study with crossover&#xD;
      component will evaluate the GABAAalpha5 receptor expression, occupancy and functional&#xD;
      connectivity in the brains of individuals with Down syndrome and healthy controls following&#xD;
      single dose RG1662. Participants will receive a single dose of placebo before the imaging&#xD;
      session (PET and MRI), and a single dose of RG1662 before the second imaging session.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brain GABAA receptor alpha5 subunit localization/density assessed by positron emission tomography (PET)</measure>
    <time_frame>approximately 1 day</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Brain GABAA receptor alpha5 subunit occupancy following single dose of RG1662</measure>
    <time_frame>approximately 1 day</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation of RG1662 plasma concentrations and GABAAalpha5 receptor occupancy</measure>
    <time_frame>approximately 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety: Incidence of adverse events</measure>
    <time_frame>approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resting state functional brain connectivity following a single dose of either RG1662 or placebo, assessed by functional magnetic resonance imaging (fMRI)</measure>
    <time_frame>approximately 1 day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional brain connectivity of individuals with Down syndrome versus healthy controls receiving placebo</measure>
    <time_frame>approximately 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Healthy Volunteer, Down Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>RG1662</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RG1662</intervention_name>
    <description>Single oral dose</description>
    <arm_group_label>RG1662</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Single oral dose</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy controls and individuals with Down syndrome:&#xD;
&#xD;
          -  Male and female adults, 18 to 40 years of age&#xD;
&#xD;
          -  Body mass index (BMI) 18 - 40 kg/m2 inclusive&#xD;
&#xD;
          -  Females of child-bearing potential and males with female partners of child-bearing&#xD;
             potential must agree to use two medically approved methods of contraception, one of&#xD;
             which must be a barrier method, for the duration of the study and for 4 months after&#xD;
             the last study drug administration&#xD;
&#xD;
          -  Clinical laboratory values within normal limits or abnormalities considered not&#xD;
             significant by the investigator and sponsor; individuals with thyroid disease may be&#xD;
             included in the study provided they are euthyroid and stable on treatment for at least&#xD;
             one month prior to screening&#xD;
&#xD;
        Individuals with Down syndrome must also meet the following:&#xD;
&#xD;
          -  Diagnosis of Down syndrome confirmed by karyotype; subjects may have free trisomy 21&#xD;
             or Robertsonian translocations; mosaic Down syndrome will be excluded&#xD;
&#xD;
          -  Individuals must have a parent or other reliable caregiver who agrees to accompany the&#xD;
             inidvidual to all clinic visits, provide information about the individual as required&#xD;
             by protocol, and be willing to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Regular smoker (&gt;5 cigarettes or equivalent: 3 cigars, 6 cigarillos, 3 pipes per day)&#xD;
&#xD;
          -  Concomitant disease or condition or any clinically significant finding at screening&#xD;
             that could interfere with, or for which the treatment might interfere with the conduct&#xD;
             of the study, or that would, in the opinion of the investigator, pose an unacceptable&#xD;
             risk to the subject in this study&#xD;
&#xD;
          -  Severe head trauma or CNS infections (e.g. meningitis)&#xD;
&#xD;
          -  History of epilepsy or seizures other than benign febrile convulsions of childhood&#xD;
&#xD;
          -  Any confirmed significant allergic reactions against any drug, anaphylaxis or severe&#xD;
             environmental allergies as judged by the investigator&#xD;
&#xD;
          -  Positive for hepatitis B, hepatitis C or HIV infection&#xD;
&#xD;
          -  Positive urine test at screening or at follow-up for drugs of abuse, or positive&#xD;
             alcohol breath test at screening and prior to dosing&#xD;
&#xD;
          -  Previous inclusion in research and/or medical protocol involving nuclear medicine, PET&#xD;
             or radiological investigations with significant radiation burden (as defined by&#xD;
             protocol)&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Individuals with evidence or meeting clinical diagnosis of dementia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>NW10 7EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>September 1, 2015</last_update_submitted>
  <last_update_submitted_qc>September 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 2, 2015</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>Down Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01667367
org study id: BP25611
secondary id: 2012-001301-24
nct id: NCT01667367
lead sponsor: 
This single-center, single-blind, placebo-controlled, parallel-group study with crossover
      component will evaluate the GABAAalpha5 receptor expression, occupancy and functional
      connectivity in the brains of individuals with Down syndrome and healthy controls following
      single dose RG1662. Participants will receive a single dose of placebo before the imaging
      session (PET and MRI), and a single dose of RG1662 before the second imaging session.
allocation: Randomized
intervention model: Crossover Assignment
masking: Single (Participant)
measure: Brain GABAA receptor alpha5 subunit localization/density assessed by positron emission tomography (PET)
time frame: approximately 1 day
measure: Brain GABAA receptor alpha5 subunit occupancy following single dose of RG1662
time frame: approximately 1 day
measure: Correlation of RG1662 plasma concentrations and GABAAalpha5 receptor occupancy
time frame: approximately 12 months
measure: Safety: Incidence of adverse events
time frame: approximately 12 months
measure: Resting state functional brain connectivity following a single dose of either RG1662 or placebo, assessed by functional magnetic resonance imaging (fMRI)
time frame: approximately 1 day
measure: Functional brain connectivity of individuals with Down syndrome versus healthy controls receiving placebo
time frame: approximately 12 months
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: RG1662
arm group type: Experimental
intervention type: Drug
intervention name: RG1662
description: Single oral dose
arm group label: RG1662
intervention type: Drug
intervention name: placebo
description: Single oral dose
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Down Syndrome
mesh term: Syndrome