<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/NCT01733654</url>
  </required_header>
  <id_info>
    <org_study_id>23708</org_study_id>
    <nct_id>NCT01733654</nct_id>
  </id_info>
  <brief_title>Investigate Efficacy &amp; Safety of RO4995819 vs. Placebo as Adjunct Tx in Patients w/Major Depressive Disorder</brief_title>
  <official_title>A Multi-center Randomized Double-blind Placebo-controlled Parallel-group Study to Investigate Efficacy and Safety of RO4995819 vs Placebo, as Adjunct Therapy in Patients w/Major Depressive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to explore the efficacy of 6 weeks treatment of an&#xD;
      investigational medication, RO4995819, versus placebo as adjunctive therapy in patients with&#xD;
      major depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators hope to learn the efficacy of 6 weeks treatment of RO4995819 versus placebo&#xD;
      as adjunctive therapy in patients with MDD having inadequate response to ongoing&#xD;
      antidepressant treatment based on mean change in Montgomery Asberg Depression Rating Scale&#xD;
      (MADRS) scores from baseline to end of treatment.&#xD;
&#xD;
      This knowledge is valuable because it is a new medication, which may have utility in the&#xD;
      population of patients with major depressive disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    no participants enrolled&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Montgomery Asberg Depression Rating Scale</measure>
    <time_frame>6 weeks</time_frame>
    <description>The investigators hope to learn the efficacy of 6 weeks treatment of RO4995819 versus placebo as adjunctive therapy in patients with MDD having inadequate response to ongoing antidepressant treatment based on mean change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline to end of treatment. This knowledge is valuable because it is a new medication, which may have utility in the population of patients with major depressive disorder.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Depression</condition>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>RO4995819 5mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>RO4995819 5mgX6wks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RO4995819 15mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>RO4995819 15mg X 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RO4995819 30mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>RO4995819 30mg X 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo X 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RO4995819</intervention_name>
    <description>The investigation of RO4995819 as adjunctive therapy in MDD patients is supported by preclinical and clinical evidence implicating dysfunction of glutamatergic pathways in the pathophysiology of depression and cognitive disorders, and accumulated evidence of the antidepressant and procognitive effects of mGlu2/3 antagonism.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>RO4995819 15mg</arm_group_label>
    <arm_group_label>RO4995819 30mg</arm_group_label>
    <arm_group_label>RO4995819 5mg</arm_group_label>
    <other_name>RO4995819, 5mg</other_name>
    <other_name>RO4995819, 15mg</other_name>
    <other_name>RO4995819, 30mg</other_name>
    <other_name>Placebo, (a pill that does not contain active drug)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients are eligible for enrollment in this study if they meet all of the following&#xD;
        criteria:&#xD;
&#xD;
          1. An outpatient w/a primary diagnosis of major depressive disorder w/out psychotic&#xD;
             features&#xD;
&#xD;
          2. Inadequate response to current, ongoing antidepressant tx of SSRI/SNRI.&#xD;
&#xD;
          3. Having at least 1 but no more than 2 antidepressant treatment failures w/in the index&#xD;
             depressive episode&#xD;
&#xD;
          4. Dose/duration of antidepressant treatment in index episode can be verified by&#xD;
             documentation from one of following:&#xD;
&#xD;
               1. Med records;&#xD;
&#xD;
               2. Pharmacy records;&#xD;
&#xD;
               3. Treating and/or referring physician (indicating medication, dose, dates of&#xD;
                  treatment).&#xD;
&#xD;
          5. Documentation of clinical/treatment history must be available.&#xD;
&#xD;
          6. Index depressive episode started w/in 1 year of screening.&#xD;
&#xD;
          7. Confirmed compliance w/current SSRI/SNRI treatment based on blood screen.&#xD;
&#xD;
          8. Existing med regimens should be stable for 6 wks prior to screening&#xD;
&#xD;
          9. 18-65 y.o. at time of consent&#xD;
&#xD;
         10. BMI 18.0 to 35.0 kg/m2 inc.&#xD;
&#xD;
         11. Patients w/reproductive potential must agree to use specified contraceptive protection&#xD;
             during tx period and for at least 90 days after last dose of study drug:&#xD;
&#xD;
               -  Males w/partners of childbearing potential or partners must use a barrier method&#xD;
                  of contraception or remain sexually abstinent.&#xD;
&#xD;
               -  Females who are not either surgically sterile (tubal ligation, removal of ovaries&#xD;
                  or uterus) or post-menopausal (no spontaneous menstrual periods for at least 1 yr&#xD;
                  confirmed by a hormone panel [FSH and 17βestradiol])must agree to use 2 adequate&#xD;
                  methods of contraception, including at least one method w/ failure rate of &lt; 1%&#xD;
                  per yr (e.g., hormonal implants, combined oral contraceptives, vasectomized&#xD;
                  partner, abstinence).&#xD;
&#xD;
         12. Able to participate and willing to give written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients are excluded from this study if the answer is 'yes' to any of the following:&#xD;
&#xD;
        Current and past treatment history:&#xD;
&#xD;
          1. Currently receiving tx w/3 or more antidepressants.&#xD;
&#xD;
          2. Currently receiving tx w/prohibited meds.&#xD;
&#xD;
          3. Significant ongoing use of high doses of barbiturates, benzodiazepines or other&#xD;
             anxiolytic drugs.&#xD;
&#xD;
          4. Previously received RO4995819.&#xD;
&#xD;
          5. Participated in investigational drug or device study w/in 6 mos of screening or in&#xD;
             index depressive episode.&#xD;
&#xD;
          6. History of non-response to Electroconvulsive Therapy (ECT), Vagus Nerve Stimulation&#xD;
             (VNS),or Repetitive Transcranial Magnetic Stimulation (RTMS).&#xD;
&#xD;
          7. Planning to begin/change current regimen of individual psychotherapy including&#xD;
             cognitive behavioral therapy during the 6 week treatment period of the study and the&#xD;
             first 2 weeks of follow-up.&#xD;
&#xD;
          8. Present DSM-IV-TR axis I diagnosis except for anxiety comorbidity&#xD;
&#xD;
          9. Past or present psychotic symptoms.&#xD;
&#xD;
         10. Mood disorder due to medical condition or substance use/abuse/dependence.&#xD;
&#xD;
         11. Established personality disorder&#xD;
&#xD;
         12. Alcohol and/or substance abuse/dependence during the last 6 months.&#xD;
&#xD;
         13. A significant risk for suicidal behavior&#xD;
&#xD;
         14. Past or present neurological disorder.&#xD;
&#xD;
         15. Present eating disorder&#xD;
&#xD;
         16. Abnormal thyroid function.&#xD;
&#xD;
         17. Active upper gastrointestinal tract disease&#xD;
&#xD;
         18. Unstable medical condition that could pose unacceptable risk to the patient in this&#xD;
             study.&#xD;
&#xD;
         19. Positive result on hepatitis B (HBV), hepatitis C (HCV), or HIV 1 and 2.&#xD;
&#xD;
         20. Positive test for drugs of abuse.&#xD;
&#xD;
         21. Abnormality on 12-lead electrocardiogram (ECG), including a QTcF of ≥450 milliseconds.&#xD;
&#xD;
         22. Lab abnormality&#xD;
&#xD;
         23. Positive pregnancy test, breast feeding,or intention to become pregnant during the&#xD;
             course of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charles DeBattista, DMH, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University Department of Psychiatry</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>October 2, 2019</last_update_submitted>
  <last_update_submitted_qc>October 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Charles DeBattista</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>depression</keyword>
  <keyword>major depressive disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</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/NCT01733654
org study id: 23708
nct id: NCT01733654
lead sponsor: 
has dmc: Yes
The purpose of the study is to explore the efficacy of 6 weeks treatment of an
      investigational medication, RO4995819, versus placebo as adjunctive therapy in patients with
      major depression.
The investigators hope to learn the efficacy of 6 weeks treatment of RO4995819 versus placebo
      as adjunctive therapy in patients with MDD having inadequate response to ongoing
      antidepressant treatment based on mean change in Montgomery Asberg Depression Rating Scale
      (MADRS) scores from baseline to end of treatment.

      This knowledge is valuable because it is a new medication, which may have utility in the
      population of patients with major depressive disorder.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Montgomery Asberg Depression Rating Scale
time frame: 6 weeks
description: The investigators hope to learn the efficacy of 6 weeks treatment of RO4995819 versus placebo as adjunctive therapy in patients with MDD having inadequate response to ongoing antidepressant treatment based on mean change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline to end of treatment. This knowledge is valuable because it is a new medication, which may have utility in the population of patients with major depressive disorder.
arm group label: RO4995819 5mg
arm group type: Active Comparator
description: RO4995819 5mgX6wks
arm group label: RO4995819 15mg
arm group type: Active Comparator
description: RO4995819 15mg X 6 weeks
arm group label: RO4995819 30mg
arm group type: Active Comparator
description: RO4995819 30mg X 6 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo X 6 weeks
intervention type: Biological
intervention name: RO4995819
description: The investigation of RO4995819 as adjunctive therapy in MDD patients is supported by preclinical and clinical evidence implicating dysfunction of glutamatergic pathways in the pathophysiology of depression and cognitive disorders, and accumulated evidence of the antidepressant and procognitive effects of mGlu2/3 antagonism.
arm group label: Placebo
arm group label: RO4995819 15mg
arm group label: RO4995819 30mg
arm group label: RO4995819 5mg
other name: RO4995819, 5mg
other name: RO4995819, 15mg
other name: RO4995819, 30mg
other name: Placebo, (a pill that does not contain active drug)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Charles DeBattista, DMH, MD
role: Principal Investigator
affiliation: Stanford University Department of Psychiatry
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Charles DeBattista
investigator title: Principle Investigator
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major