<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/NCT02205073</url>
  </required_header>
  <id_info>
    <org_study_id>BP29412</org_study_id>
    <secondary_id>2014-000867-42</secondary_id>
    <nct_id>NCT02205073</nct_id>
  </id_info>
  <brief_title>A Phase 1, Randomized, Double-blind, Placebo-controlled Crossover Study of RG7314 on the Potential Regulation of Higher Brain Functions in Healthy Male Participants: Proof of Mechanism</brief_title>
  <official_title>A RANDOMIZED, DOUBLE-BLIND, THREE PERIOD CROSS-OVER, PLACEBO CONTROLLED, PROOF OF MECHANISM STUDY TO INVESTIGATE THE EFFECT OF RG7314 ON VASOPRESSIN (AVP) PATHWAY ACTIVATION IN HEALTHY MALE 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 is a single site, randomized, double-blind, three period cross-over, placebo-controlled,&#xD;
      proof of mechanism study in healthy male subjects. The study will investigate whether the&#xD;
      directionality of brain activity and connectivity in response to intranasal vasopressin&#xD;
      treatment is similar to earlier studies and explores the effect of short-term treatment with&#xD;
      RG7314 on functional MRI as a pharmacodynamic marker. While in the scanner, the participants&#xD;
      will be asked to perform a face matching task and a Theory of Mind task, among other&#xD;
      assessments. Participants' exposure to study drug will be assessed and all participants will&#xD;
      receive follow-up examination 1 and 4 weeks after last dose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Replication of AVP-induced inhibition of anterior cingulate cortex (ACC) activity, as measured by BOLD fMRI during a face matching task, differences between treatments</measure>
    <time_frame>After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Replication of AVP-induced inhibition of functional connectivity, as measured by BOLD fMRI during a face matching task, differences between treatments</measure>
    <time_frame>After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of RG7314 on the modulation of AVP pathway effects on ACC activity, as measured by BOLD fMRI during a face matching task, differences between treatments</measure>
    <time_frame>After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (AEs)</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of RG7314 on brain activity modulated by AVP during an implicit and explicit emotional face processing task as evaluated by BOLD fMRI</measure>
    <time_frame>After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of RG7314 on brain activity modulated by AVP during a Theory of Mind task, as evaluated by BOLD fMRI</measure>
    <time_frame>After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RG7314 plasma concentrations</measure>
    <time_frame>0h, 2:20h, 3h to 4:30h, 4:30h postdose on Days 6, 20, and 34</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>Dosing Period 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosing Period 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosing Period 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo RD + AVP SD</intervention_name>
    <description>Placebo (matching to study drug) repeat doses + intranasal AVP single dose</description>
    <arm_group_label>Dosing Period 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo RD + Placebo SD</intervention_name>
    <description>Placebo (matching to study drug) repeat doses + intranasal Placebo (matching to intranasal AVP) single dose</description>
    <arm_group_label>Dosing Period 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RG7314 RD + AVP SD</intervention_name>
    <description>RG7314 repeat doses + intranasal AVP single dose</description>
    <arm_group_label>Dosing Period 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Right-handed, healthy non-smoker male adults, 18 to 45 years of age&#xD;
&#xD;
          -  A body mass index between 18 to 32 kg/m2 inclusive and total weight in the range of&#xD;
             50-100 kg&#xD;
&#xD;
          -  Participants and their partners of childbearing potential must use 2 methods of&#xD;
             contraception, one of which must be a barrier method for the duration of the study and&#xD;
             for 90 days after the last dose&#xD;
&#xD;
          -  In the investigator's opinion, the subject is deemed appropriate for participation in&#xD;
             the study, capable of following the study schedule of assessments and complying with&#xD;
             the study restrictions and discontinuation of prohibited medication will not pose&#xD;
             undue risks to the participants&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of alcohol and/or substance abuse/dependence&#xD;
&#xD;
          -  History of relapsing or current psychiatric or neurological disorders&#xD;
&#xD;
          -  Participants who, in the Investigator's judgment, pose a suicidal risk, or any subject&#xD;
             with a history of suicidal attempts or behavior&#xD;
&#xD;
          -  Positive results for serology test for HIV, Hepatitis B, hepatitis C viruses&#xD;
&#xD;
          -  Confirmed (e.g. 2 consecutive measurements) clinically significant abnormality on&#xD;
             12-lead electrocardiogram (ECG), including a QTcF of &gt;/= 450 milliseconds&#xD;
&#xD;
          -  Confirmed clinically significant abnormality in vital signs, clinical chemistry and/or&#xD;
             urinalysis&#xD;
&#xD;
          -  Active stomach ulcer disease or active gastrointestinal bleeding&#xD;
&#xD;
          -  Personal or family history (first or second degree relatives) of cerebral aneurysm&#xD;
&#xD;
          -  Personal history of stroke or traumatic head injury&#xD;
&#xD;
          -  Confirmed clinically significant abnormality in parameters of hematology or&#xD;
             coagulation&#xD;
&#xD;
          -  History of coagulopathies, bleeding disorders or blood dyscrasias&#xD;
&#xD;
          -  History of hematological malignancy or myelosuppression (including iatrogenic).&#xD;
&#xD;
          -  Contraindications for MRI scans or any brain/head abnormalities restricting MRI&#xD;
             eligibility&#xD;
&#xD;
          -  Fulfillment of any of the MRI contraindications on the standard radiography screening&#xD;
             questionnaire&#xD;
&#xD;
          -  Use of prohibited medications within 2 weeks prior to randomization, or 5 half-lives&#xD;
             (whichever is longer)&#xD;
&#xD;
          -  Participation in an investigational drug study within 90 days prior to randomization&#xD;
&#xD;
          -  Donation or loss of blood over 500 mL within three months prior to randomization&#xD;
&#xD;
          -  Chronic rhinitis, allergic rhinitis, nasal polyps or any other nasal pathology that&#xD;
             may affect the absorption of intranasal AVP according to investigator judgment&#xD;
&#xD;
          -  Concomitant disease, condition or treatment which might interfere with the conduct of&#xD;
             the study, or what would, in the opinion of the investigator, pose an unacceptable&#xD;
             risk to the subject in this study&#xD;
&#xD;
          -  Unwilling or unable to comply with the following lifestyle guidelines: (1)&#xD;
             participants will abstain from alcohol for the entire study participation; (2)&#xD;
             abstinence from any psychoactive agents or drugs of abuse for the duration of the&#xD;
             study period; (3) participants should abstain from unusual strenuous exercise&#xD;
             throughout the entire study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 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>Leiden</city>
        <zip>2333</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>June 19, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>July 1, 2016</last_update_submitted>
  <last_update_submitted_qc>July 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02205073
org study id: BP29412
secondary id: 2014-000867-42
nct id: NCT02205073
lead sponsor: 
This is a single site, randomized, double-blind, three period cross-over, placebo-controlled,
      proof of mechanism study in healthy male subjects. The study will investigate whether the
      directionality of brain activity and connectivity in response to intranasal vasopressin
      treatment is similar to earlier studies and explores the effect of short-term treatment with
      RG7314 on functional MRI as a pharmacodynamic marker. While in the scanner, the participants
      will be asked to perform a face matching task and a Theory of Mind task, among other
      assessments. Participants' exposure to study drug will be assessed and all participants will
      receive follow-up examination 1 and 4 weeks after last dose.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Replication of AVP-induced inhibition of anterior cingulate cortex (ACC) activity, as measured by BOLD fMRI during a face matching task, differences between treatments
time frame: After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo
measure: Replication of AVP-induced inhibition of functional connectivity, as measured by BOLD fMRI during a face matching task, differences between treatments
time frame: After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo
measure: Effect of RG7314 on the modulation of AVP pathway effects on ACC activity, as measured by BOLD fMRI during a face matching task, differences between treatments
time frame: After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo
measure: Incidence of adverse events (AEs)
time frame: Up to 12 weeks
measure: Effect of RG7314 on brain activity modulated by AVP during an implicit and explicit emotional face processing task as evaluated by BOLD fMRI
time frame: After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo
measure: Effect of RG7314 on brain activity modulated by AVP during a Theory of Mind task, as evaluated by BOLD fMRI
time frame: After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo
measure: RG7314 plasma concentrations
time frame: 0h, 2:20h, 3h to 4:30h, 4:30h postdose on Days 6, 20, and 34
arm group label: Dosing Period 1
arm group type: Placebo Comparator
arm group label: Dosing Period 2
arm group type: Active Comparator
arm group label: Dosing Period 3
arm group type: Experimental
intervention type: Drug
intervention name: Placebo RD + AVP SD
description: Placebo (matching to study drug) repeat doses + intranasal AVP single dose
arm group label: Dosing Period 2
intervention type: Drug
intervention name: Placebo RD + Placebo SD
description: Placebo (matching to study drug) repeat doses + intranasal Placebo (matching to intranasal AVP) single dose
arm group label: Dosing Period 1
intervention type: Drug
intervention name: RG7314 RD + AVP SD
description: RG7314 repeat doses + intranasal AVP single dose
arm group label: Dosing Period 3
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: Netherlands
responsible party type: Sponsor