<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/NCT01701089</url>
  </required_header>
  <id_info>
    <org_study_id>BP28253</org_study_id>
    <nct_id>NCT01701089</nct_id>
  </id_info>
  <brief_title>A Study of RO4602522 in Patients With Alzheimer Disease and in Healthy Volunteers</brief_title>
  <official_title>An Open-Label, Parallel Group Study to Assess the Inhibition of Brain MAO-B by RO4602522 After Repeated Dosing in Patients With Alzheimer's Disease and in Healthy Control Subjects</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 open-label, multiple dose, parallel group study will assess the monoamine oxidase in the&#xD;
      brain by in vivo positron emission tomography (PET) and safety of RO4602522 in patients with&#xD;
      Alzheimer disease and in healthy volunteers. Patients and volunteers will receive multiple&#xD;
      doses of RO4602522 and up to three injections of C11-L-deprenyl-D2 used in the PET.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in monoamine oxidase (MAO-B) enzyme activity as measured by in vivo positron emission tomography (PET)</measure>
    <time_frame>Days 1, 14, and between days 15 and 34</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Plasma concentration of RO4602522</measure>
    <time_frame>Days 1, 8, 14, and between Days 15 and 34</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction of 11C-L-deprenyl-D2 tracer uptake by in vivo positron emission tomography (PET)</measure>
    <time_frame>Days 1, 14, and between days 15 and 34</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety: incidence of adverse events</measure>
    <time_frame>35 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Healthy Volunteer, Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>RO4602522 Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>RO4602522 Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>11C-L-deprenyl-D2</intervention_name>
    <description>Intravenous injection of 11C-L-deprenyl-D2 before positron emission tomography (PET); up to 3 injections in total</description>
    <arm_group_label>RO4602522 Group 1</arm_group_label>
    <arm_group_label>RO4602522 Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO4602522</intervention_name>
    <description>Multiple doses of RO4602522 for 14 days</description>
    <arm_group_label>RO4602522 Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO4602522</intervention_name>
    <description>Multiple doses of RO4602522 for up to 17 days</description>
    <arm_group_label>RO4602522 Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        General:&#xD;
&#xD;
          -  Adults between 50-80 years of age. Females must be of non-child-bearing potential or&#xD;
             if of child-bearing potential must use an acceptable form of contraception&#xD;
&#xD;
          -  Body mass index (BMI) 18.0-32.0 kg/m2 inclusive&#xD;
&#xD;
        Healthy volunteers:&#xD;
&#xD;
          -  Healthy, with no clinically relevant finding on physical examination at screening and&#xD;
             Day -1&#xD;
&#xD;
          -  No suspicion of cognitive impairment/early dementia from neuropsychological battery as&#xD;
             judged by the investigator&#xD;
&#xD;
          -  Able to participate and willing to give informed consent, and comply with the study&#xD;
             restrictions.&#xD;
&#xD;
        Alzheimer Disease (AD) patients:&#xD;
&#xD;
          -  Probable Alzheimer's disease, based on the National Institute of Neurological and&#xD;
             Communicative&#xD;
&#xD;
          -  Disorders and Stroke (NINCDS/ADRDA) and DSM-IV criteria&#xD;
&#xD;
          -  Have a MMSE score at screening between 17 and 26 inclusive&#xD;
&#xD;
          -  Modified Hachinski Ischemia Scale score of &lt;/=4&#xD;
&#xD;
          -  A neuroimaging evaluation of the brain by MRI which supports a diagnosis of AD, with&#xD;
             no evidence of focal disease to account for dementia or MRI exclusion criteria&#xD;
&#xD;
          -  Medications taken for symptomatic treatment of AD must be maintained on a stable&#xD;
             dosage regimen for at least 1 month before Day 1.&#xD;
&#xD;
          -  Able to participate in all scheduled evaluations&#xD;
&#xD;
          -  The patient has an appropriate caregiver or community dwelling with caregiver capable&#xD;
             of accompanying subject on all visits to the center as judged by the investigator.&#xD;
&#xD;
          -  In the opinion of the investigator the patient and caregiver will be compliant and&#xD;
             have a high probability of completing the study.&#xD;
&#xD;
          -  Signed and dated written informed consent obtained from the patient, co-signed by the&#xD;
             patient's closest relatives and legally authorized representative, as required by&#xD;
             national law for patients that are incapable of giving informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General:&#xD;
&#xD;
          -  Any active disease of the gastrointestinal (GI) system, liver, or kidneys that could&#xD;
             result in altered absorption, excess accumulation, or impaired metabolism or excretion&#xD;
             of drugs, including a history of major upper or middle GI tract surgery or current&#xD;
             significant chronic disease of the GI tract&#xD;
&#xD;
          -  Clinically relevant abnormal history, physical findings, ECG, or laboratory values at&#xD;
             the screening assessment&#xD;
&#xD;
          -  History of cancer in the past five years, except for fully treated local basal&#xD;
             carcinoma, or fully treated carcinoma in situ of cervix&#xD;
&#xD;
          -  Any major illness occurring within 1 month prior to the screening examination or&#xD;
             febrile illness within 5 days prior to first dose&#xD;
&#xD;
          -  History of psychotropic medicine abuse&#xD;
&#xD;
          -  At risk of suicide in the opinion of the investigator or having a Yes to question&#xD;
             number 4 or 5 of the Suicidal Ideation section of the C-SSRS&#xD;
&#xD;
          -  Administration of ionizing radiation or radioisotope for research, diagnostics test or&#xD;
             therapy within 12 months prior to the present study which would exceed the local&#xD;
             yearly radiation dose exposures for participation in research studies (except for&#xD;
             dental x-rays, minimal plain films such as chest and ankle X-rays) or subjects who&#xD;
             regularly work with ionizing radiation or radioactive material.&#xD;
&#xD;
          -  Participation in a clinical study with an investigational drug within 3 months before&#xD;
             screening&#xD;
&#xD;
          -  Positive test for hepatitis B, hepatitis C, or HIV at screening&#xD;
&#xD;
          -  Loss or donation of more than 450 mL blood in the 4 months before screening or&#xD;
             donation of plasma within 14 days of screening.&#xD;
&#xD;
          -  History of drug abuse or evidence of drug abuse in urine test performed at screening&#xD;
&#xD;
          -  Current alcohol abuse, or regular intake of more than 2 units of alcohol daily&#xD;
&#xD;
          -  Coffee (or tea) consumption &gt; 5 cups per day or xanthine containing drinks &gt;/1.5&#xD;
             liter/day&#xD;
&#xD;
        Healthy volunteers:&#xD;
&#xD;
          -  Family history of Alzheimer's disease in 1st and 2nd degree relative under 75 years.&#xD;
&#xD;
          -  Evidence or history of clinically significant neurological or psychiatric disorders.&#xD;
&#xD;
        AD Patients:&#xD;
&#xD;
          -  Any neurological or psychiatric condition not specified in exceptions&#xD;
&#xD;
          -  Previous immunization therapy for AD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 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>Stockholm</city>
        <zip>141 86</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>November 1, 2016</last_update_submitted>
  <last_update_submitted_qc>November 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 2, 2016</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>Selegiline</mesh_term>
  </intervention_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/NCT01701089
org study id: BP28253
nct id: NCT01701089
lead sponsor: 
This open-label, multiple dose, parallel group study will assess the monoamine oxidase in the
      brain by in vivo positron emission tomography (PET) and safety of RO4602522 in patients with
      Alzheimer disease and in healthy volunteers. Patients and volunteers will receive multiple
      doses of RO4602522 and up to three injections of C11-L-deprenyl-D2 used in the PET.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in monoamine oxidase (MAO-B) enzyme activity as measured by in vivo positron emission tomography (PET)
time frame: Days 1, 14, and between days 15 and 34
measure: Pharmacokinetics: Plasma concentration of RO4602522
time frame: Days 1, 8, 14, and between Days 15 and 34
measure: Reduction of 11C-L-deprenyl-D2 tracer uptake by in vivo positron emission tomography (PET)
time frame: Days 1, 14, and between days 15 and 34
measure: Safety: incidence of adverse events
time frame: 35 days
arm group label: RO4602522 Group 1
arm group type: Experimental
arm group label: RO4602522 Group 2
arm group type: Experimental
intervention type: Drug
intervention name: 11C-L-deprenyl-D2
description: Intravenous injection of 11C-L-deprenyl-D2 before positron emission tomography (PET); up to 3 injections in total
arm group label: RO4602522 Group 1
arm group label: RO4602522 Group 2
intervention type: Drug
intervention name: RO4602522
description: Multiple doses of RO4602522 for 14 days
arm group label: RO4602522 Group 1
intervention type: Drug
intervention name: RO4602522
description: Multiple doses of RO4602522 for up to 17 days
arm group label: RO4602522 Group 2
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Selegiline