<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/NCT03814733</url>
  </required_header>
  <id_info>
    <org_study_id>RAP-PK-18</org_study_id>
    <nct_id>NCT03814733</nct_id>
  </id_info>
  <brief_title>Assessment of Effect of Rapastinel on Driving Performance</brief_title>
  <official_title>A Phase 1, Randomized, Double-blind, Double-dummy, Placebo-controlled, 5-period, Crossover Study Assessing the Effects of Rapastinel Compared to Alprazolam, Ketamine, and Placebo on Simulated Driving Performance in Normal Healthy Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Naurex, Inc, an affiliate of Allergan plc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Naurex, Inc, an affiliate of Allergan plc</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Based on the pharmacological class of rapastinel, this study will be conducted to evaluate&#xD;
      the participant's driving performance after single IV doses of rapastinel as compared with&#xD;
      single oral doses of alprazolam, a benzodiazepine that demonstrates driving impairment, and&#xD;
      placebo in healthy participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2018</start_date>
  <completion_date type="Actual">April 3, 2019</completion_date>
  <primary_completion_date type="Actual">March 29, 2019</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>Simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with placebo and positive control (alprazolam)</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with a clinical comparator (ketamine)</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Karolinska Sleepiness Scale (KSS)</measure>
    <time_frame>Day 1 of each intervention</time_frame>
    <description>The KSS is a participant self-reported measure of situational sleepiness and provides an assessment of alertness/sleepiness. The KSS is a 9-point categorical scale, where 1 = &quot;extremely alert&quot; and 9 = &quot;extremely sleepy-fighting sleep&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-perceived safety to drive (&quot;Right now do you feel safe to drive?)</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Analog Scale to assess participant's motivation and self-appraisal of their driving performance</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CogScreen SDC Test</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of abnormal lane exceedance events</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Speed (mph)</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total collisions</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of exceeded cornering speed threshold events</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Divided attention: average number of correct responses</measure>
    <time_frame>Day 1 of each intervention</time_frame>
    <description>Participants are asked to answer periodic questions during the driving simulation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Divided attention: average number of errors</measure>
    <time_frame>Day 1 of each intervention</time_frame>
    <description>Participants are asked to answer periodic questions during the driving simulation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Divided attention: average reaction time</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rapastinel blood plasma concentration</measure>
    <time_frame>Day 1 of each intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Up to 66 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of abnormal electrocardiograms</measure>
    <time_frame>Up to 66 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Columbia-Suicide Severity Rating Scale</measure>
    <time_frame>Up to 66 days</time_frame>
    <description>The C-SSRS is a clinician-ratedinstrument that reports theseverity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (least severe) to 5 (most severe).</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Driving Performance</condition>
  <arm_group>
    <arm_group_label>Rapastinel High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rapastinel Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alprazolam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for Rapastinel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for Alprazolam</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for Ketamine</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapastinel</intervention_name>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
    <arm_group_label>Rapastinel High Dose</arm_group_label>
    <arm_group_label>Rapastinel Low Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alprazolam</intervention_name>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
    <arm_group_label>Alprazolam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
    <arm_group_label>Ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapastinel Matched Placebo</intervention_name>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
    <arm_group_label>Placebo for Rapastinel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alprazolam Matched Placebo</intervention_name>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
    <arm_group_label>Placebo for Alprazolam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine Matched Placebo</intervention_name>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.</description>
    <arm_group_label>Placebo for Ketamine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Participant possesses a valid driver's license and is an active driver. Drives a&#xD;
             minimum of 5,000 miles (about 8,000 km) per year for the previous 3 years.&#xD;
&#xD;
          -  Participant has a regular sleep pattern, is not engaged in shift-work, and in general,&#xD;
             has at least 7 hours of sleep each night (bedtime occurs between 21:00 and 24:00&#xD;
             hours).&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  A history within 2 years of, or current intervention for, a sleeping disorder&#xD;
             (including excessive snoring, obstructive sleep apnea) or a chronic painful condition&#xD;
             that interferes with the participant's sleep.&#xD;
&#xD;
          -  A history of difficulty in falling asleep or staying asleep in the previous 3 months&#xD;
             that is considered clinically significant by the investigator.&#xD;
&#xD;
          -  Participant has traveled across 1 or more time zones (transmeridian travel) in the 14&#xD;
             days before study intervention or is expected to travel across 1 or more time zones&#xD;
             during the study.&#xD;
&#xD;
          -  Expected to work on a rotating shift during their participation in the study.&#xD;
&#xD;
          -  Participant works a night shift.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheng Fang Su</last_name>
    <role>Study Director</role>
    <affiliation>Allergan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network</name>
      <address>
        <city>San Clemente</city>
        <state>California</state>
        <zip>92673</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Algorithme Pharma</name>
      <address>
        <city>Aurora</city>
        <state>Ontario</state>
        <zip>L4G 0A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>July 9, 2019</last_update_submitted>
  <last_update_submitted_qc>July 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Alprazolam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03814733
org study id: RAP-PK-18
nct id: NCT03814733
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Based on the pharmacological class of rapastinel, this study will be conducted to evaluate
      the participant's driving performance after single IV doses of rapastinel as compared with
      single oral doses of alprazolam, a benzodiazepine that demonstrates driving impairment, and
      placebo in healthy participants.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with placebo and positive control (alprazolam)
time frame: Day 1 of each intervention
measure: simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with a clinical comparator (ketamine)
time frame: Day 1 of each intervention
measure: Karolinska Sleepiness Scale (KSS)
time frame: Day 1 of each intervention
description: The KSS is a participant self-reported measure of situational sleepiness and provides an assessment of alertness/sleepiness. The KSS is a 9-point categorical scale, where 1 = "extremely alert" and 9 = "extremely sleepy-fighting sleep".
measure: Self-perceived safety to drive ("Right now do you feel safe to drive?)
time frame: Day 1 of each intervention
measure: Visual Analog Scale to assess participant's motivation and self-appraisal of their driving performance
time frame: Day 1 of each intervention
measure: CogScreen SDC Test
time frame: Day 1 of each intervention
measure: Proportion of abnormal lane exceedance events
time frame: Day 1 of each intervention
measure: Average Speed (mph)
time frame: Day 1 of each intervention
measure: Total collisions
time frame: Day 1 of each intervention
measure: Number of exceeded cornering speed threshold events
time frame: Day 1 of each intervention
measure: Divided attention: average number of correct responses
time frame: Day 1 of each intervention
description: Participants are asked to answer periodic questions during the driving simulation.
measure: Divided attention: average number of errors
time frame: Day 1 of each intervention
description: Participants are asked to answer periodic questions during the driving simulation.
measure: Divided attention: average reaction time
time frame: Day 1 of each intervention
measure: Rapastinel blood plasma concentration
time frame: Day 1 of each intervention
measure: Adverse Events
time frame: Up to 66 days
measure: Proportion of abnormal electrocardiograms
time frame: Up to 66 days
measure: Columbia-Suicide Severity Rating Scale
time frame: Up to 66 days
description: The C-SSRS is a clinician-ratedinstrument that reports theseverity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (least severe) to 5 (most severe).
arm group label: Rapastinel High Dose
arm group type: Experimental
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Rapastinel Low Dose
arm group type: Experimental
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Alprazolam
arm group type: Active Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Ketamine
arm group type: Active Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Placebo for Rapastinel
arm group type: Placebo Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Placebo for Alprazolam
arm group type: Placebo Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Placebo for Ketamine
arm group type: Placebo Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
intervention type: Drug
intervention name: Rapastinel
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Rapastinel High Dose
arm group label: Rapastinel Low Dose
intervention type: Drug
intervention name: Alprazolam
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Alprazolam
intervention type: Drug
intervention name: Ketamine
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Ketamine
intervention type: Drug
intervention name: Rapastinel Matched Placebo
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Placebo for Rapastinel
intervention type: Drug
intervention name: Alprazolam Matched Placebo
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Placebo for Alprazolam
intervention type: Drug
intervention name: Ketamine Matched Placebo
description: Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.
arm group label: Placebo for Ketamine
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sheng Fang Su
role: Study Director
affiliation: Allergan
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Ketamine
mesh term: Alprazolam
sharing ipd: Undecided