<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/NCT04451187</url>
  </required_header>
  <id_info>
    <org_study_id>CR108762</org_study_id>
    <secondary_id>42847922MDD1005</secondary_id>
    <secondary_id>2019-004913-15</secondary_id>
    <nct_id>NCT04451187</nct_id>
  </id_info>
  <brief_title>A Study of Oral Seltorexant as an add-on Medication to an Antidepressant on On-road Driving Performance in Participants With Major Depressive Disorder</brief_title>
  <official_title>A Multicentric, Randomized, Double-Blind, Placebo- and Positive-Controlled 4-way Crossover Study to Evaluate the Effects of Single and Repeated Administration of Oral Seltorexant as an add-on Medication to an Antidepressant on On-Road Driving Performance in Participants With Major Depressive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of the study is to evaluate the effect of seltorexant, compared to placebo, as an&#xD;
      add-on medication to an antidepressant, on next-day driving performance as assessed by the&#xD;
      mean difference of standard deviation of lateral position (SDLP) from an on-road driving test&#xD;
      in participants with major depressive disorder (MDD).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2020</start_date>
  <completion_date type="Actual">March 16, 2023</completion_date>
  <primary_completion_date type="Actual">March 16, 2023</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test</measure>
    <time_frame>Day 2</time_frame>
    <description>In the participants with major depressive disorder (MDD), driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test to evaluate the effect of seltorexant dose 1, compared to placebo, as an add-on medication to an antidepressant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test</measure>
    <time_frame>Day 9</time_frame>
    <description>In the participants with MDD, driving performance will be assessed by the mean difference of SDLP from an on-road driving test to evaluate the effect of seltorexant dose 1, compared to placebo, as an add-on medication to an antidepressant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test</measure>
    <time_frame>Day 2 and Day 9</time_frame>
    <description>The driving performance will be assessed by the mean difference of SDLP from an on-road driving test to evaluate the effect of seltorexant doses (Dose 1 and Dose 2), compared to placebo in adult participants with major depressive disorder (MDD); and on adults and elderly participants with MDD and healthy elderly (if enrolled) (seltorexant Dose 1 and Dose 2); and on adults and elderly participants with MDD (seltorexant Dose 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Driving Performance as Assessed by Visual Analog Scale</measure>
    <time_frame>Day 2 and Day 9</time_frame>
    <description>Immediately after each driving test, participants with MDD or in healthy elderly participants (if enrolled) will indicate the perceived quality of their driving performance on a visual analog scale from 0 ('I drove exceptionally poorly') to 20 ('I drove exceptionally well') around a midpoint of 'I drove normally'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 20 weeks</time_frame>
    <description>An adverse event is any untoward medical occurrence in a clinical study participant with MDD or in healthy elderly participants (if enrolled) administered a medicinal (investigational or non investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Treatment Sequence CADB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive placebo once daily (OD) at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment C) in Period 1 followed by Dose 1 of seltorexant tablets and placebo OD at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment A) in Period 2 followed by Dose 2 of seltorexant tablets OD at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment D) in Period 3 followed by zopiclone on Day 1 and Day 8 and placebo from Day 2 to Day 7 OD at bedtime (Treatment B) in Period 4. There will be a washout period of 5 to 21 days between each period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence ABCD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3 followed by Treatment D in Period 4. There will be a washout period of 5 to 21 days between each period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence BDAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Treatment B in Period 1 followed by Treatment D in Period 2 followed by Treatment A in Period 3 followed by Treatment C in Period 4. There will be a washout period of 5 to 21 days between each period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence DCBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Treatment D in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3 followed by Treatment A in Period 4. There will be a washout period of 5 to 21 days between each period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Seltorexant Dose 1</intervention_name>
    <description>Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABCD</arm_group_label>
    <arm_group_label>Treatment Sequence BDAC</arm_group_label>
    <arm_group_label>Treatment Sequence CADB</arm_group_label>
    <arm_group_label>Treatment Sequence DCBA</arm_group_label>
    <other_name>JNJ-42847922</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Seltorexant Dose 2</intervention_name>
    <description>Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABCD</arm_group_label>
    <arm_group_label>Treatment Sequence BDAC</arm_group_label>
    <arm_group_label>Treatment Sequence CADB</arm_group_label>
    <arm_group_label>Treatment Sequence DCBA</arm_group_label>
    <other_name>JNJ-42847922</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive placebo of seltorexant OD from Day 1 to Day 8 as a part of Treatment A and C and from Day 2 and Day 7 as a part of Treatment B as per assigned treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABCD</arm_group_label>
    <arm_group_label>Treatment Sequence BDAC</arm_group_label>
    <arm_group_label>Treatment Sequence CADB</arm_group_label>
    <arm_group_label>Treatment Sequence DCBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zopiclone</intervention_name>
    <description>Participants will receive Dose 3 of zopiclone OD from Day 1 to Day 8 as a part of Treatment B as per assigned treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABCD</arm_group_label>
    <arm_group_label>Treatment Sequence BDAC</arm_group_label>
    <arm_group_label>Treatment Sequence CADB</arm_group_label>
    <arm_group_label>Treatment Sequence DCBA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant with major depressive disorder (MDD) (not applicable for elderly without&#xD;
             MDD) must meet Diagnostic and Statistical Manual of Mental Disorders-5th Edition&#xD;
             (DSM-5) diagnostic criteria for major depressive disorder (MDD) without psychotic&#xD;
             features based upon clinical assessment (DSM-5 296.20, 296.21, 296.25, 296.26, 296.30,&#xD;
             296.31, 296.35 or 296.36) and confirmed by the Mini International Neuropsychiatric&#xD;
             Interview (MINI) and the attending general physician, psychiatrist or mental health&#xD;
             practitioner. The MINI will also be conducted for elderly participants without MDD to&#xD;
             rule out major psychiatric disorders&#xD;
&#xD;
          -  Participants with MDD (not applicable for elderly without MDD) must have mild or&#xD;
             better depressive symptoms indicated by a Montgomery-Asberg Depression Rating Scale&#xD;
             (MADRS) total score of less than or equal to (&lt;=) 18 at screening&#xD;
&#xD;
          -  Participants with MDD having comorbid generalized anxiety disorder, social anxiety&#xD;
             disorder, or panic disorder for whom major depressive disorder (MDD) is considered the&#xD;
             primary diagnosis are not excluded&#xD;
&#xD;
          -  Participants with MDD (not applicable for elderly without MDD) must be receiving and&#xD;
             tolerating well any one of the following selective serotonin reuptake inhibitor (SSRI)&#xD;
             or serotonin-norepinephrine reuptake inhibitor (SNRI) for depressive symptoms in any&#xD;
             formulation and available in the participating country: citalopram, duloxetine,&#xD;
             escitalopram, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline,&#xD;
             venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at&#xD;
             therapeutic dose level) for at least 4 weeks prior to screening, and expected to&#xD;
             continue to take the same drug and dose for the duration of the study&#xD;
&#xD;
          -  Participant should be medically stable on the basis of medical history, neurological&#xD;
             examination and clinical laboratory tests performed at screening, and physical&#xD;
             examination, vital signs, and 12-lead electrocardiogram (ECG) performed at screening&#xD;
             and predose on Day 1 of Period 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants has a recent (last 3 months) history of, or current signs and symptoms of&#xD;
             severe renal insufficiency (creatinine clearance less than [&lt;]30 milliliter per minute&#xD;
             [mL/min]); clinically significant or unstable cardiovascular, respiratory,&#xD;
             gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine&#xD;
             disorders; and participants with uncontrolled type 1 or type 2 diabetes mellitus&#xD;
&#xD;
          -  Participants has clinically significant hepatic disease as defined by greater than or&#xD;
             equal to (&gt;=) 2* Upper Limit of Normal [ULN]) increase of aspartate aminotransferase&#xD;
             (AST) or alanine aminotransferase (ALT) at screening (one retest is permitted); and&#xD;
             significant liver disease including cirrhosis, ascites, active hepatitis etc. (fatty&#xD;
             liver disease or Gilbert's syndrome will be allowed as long as it does not meet the&#xD;
             above criteria)&#xD;
&#xD;
          -  Participants has current signs/symptoms of hypothyroidism or hyperthyroidism. For&#xD;
             participants with a history of thyroid disease and for participants who, regardless of&#xD;
             thyroid history have the thyroid stimulating hormone (TSH) value out of range, a free&#xD;
             thyroxine (FT4) test will be conducted. If the FT4 value is abnormal and considered to&#xD;
             be clinically significant (after discussion with the medical monitor) the participant&#xD;
             is not eligible. Participants with a pre-existing history of thyroid disease/disorder&#xD;
             who are treated with thyroid hormones need to be on a stable dosage for 3 months prior&#xD;
             to the start of the screening phase. Participants taking thyroid supplementation for&#xD;
             antidepressant purposes are not allowed in the study&#xD;
&#xD;
          -  Participants has Cushing's Disease, Addison's Disease, primary amenorrhea, or other&#xD;
             evidence of significant medical disorders of the hypothalamic-pituitary-adrenal (HPA)&#xD;
             axis&#xD;
&#xD;
          -  Participants has a lifetime history of narcolepsy and seizures (except childhood&#xD;
             seizures)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anima</name>
      <address>
        <city>Alken</city>
        <zip>3570</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum der RWTH Aachen</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
  </location_countries>
  <removed_countries>
    <country>Netherlands</country>
  </removed_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>March 30, 2023</last_update_submitted>
  <last_update_submitted_qc>March 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2023</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>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zopiclone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials/transparency.&#xD;
As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </patient_data>
  <!-- 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/NCT04451187
org study id: CR108762
secondary id: 42847922MDD1005
secondary id: 2019-004913-15
nct id: NCT04451187
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to evaluate the effect of seltorexant, compared to placebo, as an
      add-on medication to an antidepressant, on next-day driving performance as assessed by the
      mean difference of standard deviation of lateral position (SDLP) from an on-road driving test
      in participants with major depressive disorder (MDD).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test
time frame: Day 2
description: In the participants with major depressive disorder (MDD), driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test to evaluate the effect of seltorexant dose 1, compared to placebo, as an add-on medication to an antidepressant.
measure: Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test
time frame: Day 9
description: In the participants with MDD, driving performance will be assessed by the mean difference of SDLP from an on-road driving test to evaluate the effect of seltorexant dose 1, compared to placebo, as an add-on medication to an antidepressant.
measure: Driving Performance as Assessed by the Mean Difference of SDLP From an on-road Driving Test
time frame: Day 2 and Day 9
description: The driving performance will be assessed by the mean difference of SDLP from an on-road driving test to evaluate the effect of seltorexant doses (Dose 1 and Dose 2), compared to placebo in adult participants with major depressive disorder (MDD); and on adults and elderly participants with MDD and healthy elderly (if enrolled) (seltorexant Dose 1 and Dose 2); and on adults and elderly participants with MDD (seltorexant Dose 2).
measure: Participant Driving Performance as Assessed by Visual Analog Scale
time frame: Day 2 and Day 9
description: Immediately after each driving test, participants with MDD or in healthy elderly participants (if enrolled) will indicate the perceived quality of their driving performance on a visual analog scale from 0 ('I drove exceptionally poorly') to 20 ('I drove exceptionally well') around a midpoint of 'I drove normally'.
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Up to 20 weeks
description: An adverse event is any untoward medical occurrence in a clinical study participant with MDD or in healthy elderly participants (if enrolled) administered a medicinal (investigational or non investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.
arm group label: Treatment Sequence CADB
arm group type: Experimental
description: Participants will receive placebo once daily (OD) at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment C) in Period 1 followed by Dose 1 of seltorexant tablets and placebo OD at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment A) in Period 2 followed by Dose 2 of seltorexant tablets OD at bedtime for 8 consecutive days from Day 1 to Day 8 (Treatment D) in Period 3 followed by zopiclone on Day 1 and Day 8 and placebo from Day 2 to Day 7 OD at bedtime (Treatment B) in Period 4. There will be a washout period of 5 to 21 days between each period.
arm group label: Treatment Sequence ABCD
arm group type: Experimental
description: Participants will receive Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3 followed by Treatment D in Period 4. There will be a washout period of 5 to 21 days between each period.
arm group label: Treatment Sequence BDAC
arm group type: Experimental
description: Participants will receive Treatment B in Period 1 followed by Treatment D in Period 2 followed by Treatment A in Period 3 followed by Treatment C in Period 4. There will be a washout period of 5 to 21 days between each period.
arm group label: Treatment Sequence DCBA
arm group type: Experimental
description: Participants will receive Treatment D in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3 followed by Treatment A in Period 4. There will be a washout period of 5 to 21 days between each period.
intervention type: Drug
intervention name: Seltorexant Dose 1
description: Participants will receive Dose 1 of seltorexant OD from Day 1 to Day 8 as part of Treatment A as per assigned treatment sequence.
arm group label: Treatment Sequence ABCD
arm group label: Treatment Sequence BDAC
arm group label: Treatment Sequence CADB
arm group label: Treatment Sequence DCBA
other name: JNJ-42847922
intervention type: Drug
intervention name: Seltorexant Dose 2
description: Participants will receive Dose 2 of seltorexant OD from Day 1 to Day 8 as part of Treatment D as per assigned treatment sequence.
arm group label: Treatment Sequence ABCD
arm group label: Treatment Sequence BDAC
arm group label: Treatment Sequence CADB
arm group label: Treatment Sequence DCBA
other name: JNJ-42847922
intervention type: Drug
intervention name: Placebo
description: Participants will receive placebo of seltorexant OD from Day 1 to Day 8 as a part of Treatment A and C and from Day 2 and Day 7 as a part of Treatment B as per assigned treatment sequence.
arm group label: Treatment Sequence ABCD
arm group label: Treatment Sequence BDAC
arm group label: Treatment Sequence CADB
arm group label: Treatment Sequence DCBA
intervention type: Drug
intervention name: Zopiclone
description: Participants will receive Dose 3 of zopiclone OD from Day 1 to Day 8 as a part of Treatment B as per assigned treatment sequence.
arm group label: Treatment Sequence ABCD
arm group label: Treatment Sequence BDAC
arm group label: Treatment Sequence CADB
arm group label: Treatment Sequence DCBA
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
facility: 
country: Belgium
country: Germany
country: Netherlands
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Zopiclone
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.
As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency