<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/NCT03799900</url>
  </required_header>
  <id_info>
    <org_study_id>RAP-PK-12</org_study_id>
    <nct_id>NCT03799900</nct_id>
  </id_info>
  <brief_title>Assessment of Abuse Potential of Rapastinel in Humans</brief_title>
  <official_title>A Two-part, Single-dose, Randomized, Double-blind, Placebo and Active-Controlled Crossover Study to Evaluate the Abuse Potential of Rapastinel in Healthy, Non-dependent, Adult Recreational Polydrug Users</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 abuse potential of single doses of rapastinel as compared with ketamine, a NMDAR&#xD;
      antagonist that is a Schedule III dissociative anesthetic, and placebo in recreational&#xD;
      polydrug users.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Actual">March 29, 2019</completion_date>
  <primary_completion_date type="Actual">March 24, 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>Maximum effect (Emax) for &quot;At this Moment&quot; Drug Liking visual analog scale (VAS).</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
    <description>The drug liking VAS measures the participant's liking for the drug and is scored from 0 to 100, with 0 reflecting &quot;Strong disliking&quot; and 100 reflecting &quot;Strong liking&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum effect (Emax)</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum effect (Emin)</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Emax (TEmax)</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Emin (TEmin)</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time averaged area under the effect curve (TA_AUE)</measure>
    <time_frame>Treatment Phase: Hour 0 and up to 24 Hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma drug concentration (Cmax)</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUClast)</measure>
    <time_frame>Treatment Phase: Pre-dose and up to 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Part 1: 6 weeks, Part 2: 9 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of abnormal electrocardiograms</measure>
    <time_frame>Part 1: 6 weeks, Part 2: 9 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Columbia-Suicide Severity Rating Scale</measure>
    <time_frame>Part 1: 6 weeks, Part 2: 9 weeks</time_frame>
    <description>The C-SSRS is a clinician-rated instrument that reports the severity 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>13</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Human Abuse Potential</condition>
  <arm_group>
    <arm_group_label>Part 1, Cohort 1: Ketamine Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Some participants will be administered a single IV dose of ketamine on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 1: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Some participants will be administered a single IV dose of placebo on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 2: Ketamine Medium Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Some participants will be administered a single IV dose of ketamine on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 2: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Some participants will be administered a single IV dose of placebo on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 3 (Optional): Ketamine High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optional: some participants will be administered a single IV dose of ketamine on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1, Cohort 3 (Optional): Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Optional: some participants will be administered a single IV dose of placebo on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Qualification Phase: Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Qualification Phase: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive IV ketamine on Day 2 and placebo on Day 1 in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Treatment Phase: Rapastinel Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Treatment Phase: Rapastinel Medium Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Treatment Phase: Rapastinel High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Treatment Phase: Ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2, Treatment Phase: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapastinel</intervention_name>
    <description>During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
    <arm_group_label>Part 2, Treatment Phase: Rapastinel High Dose</arm_group_label>
    <arm_group_label>Part 2, Treatment Phase: Rapastinel Low Dose</arm_group_label>
    <arm_group_label>Part 2, Treatment Phase: Rapastinel Medium Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Part 1&#xD;
Part 2, Qualification Phase:&#xD;
Participants will be administered single IV doses of ketamine and placebo in a randomized crossover manner&#xD;
Part 2, Treatment Phase:&#xD;
Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
    <arm_group_label>Part 1, Cohort 1: Ketamine Low Dose</arm_group_label>
    <arm_group_label>Part 1, Cohort 2: Ketamine Medium Dose</arm_group_label>
    <arm_group_label>Part 1, Cohort 3 (Optional): Ketamine High Dose</arm_group_label>
    <arm_group_label>Part 2, Qualification Phase: Ketamine</arm_group_label>
    <arm_group_label>Part 2, Treatment Phase: Ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Part 1&#xD;
Part 2, Qualification Phase:&#xD;
Participants will be administered single IV doses of ketamine and placebo in a randomized crossover manner&#xD;
Part 2, Treatment Phase:&#xD;
Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.</description>
    <arm_group_label>Part 1, Cohort 1: Placebo</arm_group_label>
    <arm_group_label>Part 1, Cohort 2: Placebo</arm_group_label>
    <arm_group_label>Part 1, Cohort 3 (Optional): Placebo</arm_group_label>
    <arm_group_label>Part 2, Qualification Phase: Placebo</arm_group_label>
    <arm_group_label>Part 2, Treatment Phase: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must be a current recreational polydrug user&#xD;
&#xD;
          -  Have a supine systolic blood pressure (BP) ≥ 95 mm Hg and ≤ 145 mg Hg, or supine&#xD;
             diastolic BP ≥ 50 mm Hg and ≤ 90 mm Hg at the Screening Visit.&#xD;
&#xD;
          -  Have negative test results for benzoylecgonine (cocaine), methadone, barbiturates,&#xD;
             amphetamines, benzodiazepines, alcohol, oxycodone and other opioids, and phencyclidine&#xD;
             at any admission&#xD;
&#xD;
          -  Able, as assessed by the investigator, and willing to follow study instructions and&#xD;
             likely to complete all required study visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of drug or alcohol dependence (excluding nicotine and caffeine) within the&#xD;
             past 2 years&#xD;
&#xD;
          -  Suicidal risk based on the opinion of the principal investigator (or appropriately&#xD;
             trained designee)&#xD;
&#xD;
          -  History of violent or psychotic behavior when taking psychedelic drugs, or unwilling&#xD;
             to take a drug that might alter perception in a controlled setting&#xD;
&#xD;
          -  Have taken or require concomitant treatment with any CNS depressants, or cannot safely&#xD;
             discontinue these medications within 14 days (or 5 half-lives, whichever is longer)&#xD;
             before study treatment administration&#xD;
&#xD;
          -  Previously participated in an investigational study of rapastinel.&#xD;
&#xD;
          -  Participation in any other clinical investigation using an experimental drug within 30&#xD;
             days, 5 half-lives or twice the duration of the biological effect of the study&#xD;
             treatment (whichever is longer), prior to study treatment administration or is&#xD;
             concurrently enrolled in any clinical trial, judged not to be scientifically or&#xD;
             medically compatible with this study&#xD;
&#xD;
          -  Consumption of alcohol within 72 hours before administration of study treatment&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Unable to refrain from consuming caffeine or xanthine-containing compounds such as&#xD;
             tea, coffee, soft drinks, energy sports drinks or chocolate (more than 48 oz/day) from&#xD;
             48 hours before administration of study treatment.&#xD;
&#xD;
          -  Have consumed dietary supplements or other foods or beverages that may affect various&#xD;
             drug metabolizing enzymes and transporters (eg, grapefruit, grapefruit juice,&#xD;
             grapefruit-containing beverages), vegetables from the mustard green family (eg, kale,&#xD;
             broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and&#xD;
             charbroiled meats within 14 days prior to dosing or unable to refrain from consumption&#xD;
             during the study.&#xD;
&#xD;
          -  The ability to tolerate IV ketamine as judged by the Investigator, based on available&#xD;
             safety data, as well as pharmacodynamic data.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>Vince and Associates Clinical Research Inc</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>May 14, 2019</last_update_submitted>
  <last_update_submitted_qc>May 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 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>
  </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/NCT03799900
org study id: RAP-PK-12
nct id: NCT03799900
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 abuse potential of single doses of rapastinel as compared with ketamine, a NMDAR
      antagonist that is a Schedule III dissociative anesthetic, and placebo in recreational
      polydrug users.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Maximum effect (Emax) for "At this Moment" Drug Liking visual analog scale (VAS).
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
description: The drug liking VAS measures the participant's liking for the drug and is scored from 0 to 100, with 0 reflecting "Strong disliking" and 100 reflecting "Strong liking".
measure: Maximum effect (Emax)
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Minimum effect (Emin)
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Time to Emax (TEmax)
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Time to Emin (TEmin)
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Time averaged area under the effect curve (TA_AUE)
time frame: Treatment Phase: Hour 0 and up to 24 Hours post-dose
measure: Maximum plasma drug concentration (Cmax)
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUClast)
time frame: Treatment Phase: Pre-dose and up to 24 hours post-dose
measure: Adverse events
time frame: Part 1: 6 weeks, Part 2: 9 weeks
measure: Proportion of abnormal electrocardiograms
time frame: Part 1: 6 weeks, Part 2: 9 weeks
measure: Columbia-Suicide Severity Rating Scale
time frame: Part 1: 6 weeks, Part 2: 9 weeks
description: The C-SSRS is a clinician-rated instrument that reports the severity 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: Part 1, Cohort 1: Ketamine Low Dose
arm group type: Experimental
description: Some participants will be administered a single IV dose of ketamine on Day 1.
arm group label: Part 1, Cohort 1: Placebo
arm group type: Placebo Comparator
description: Some participants will be administered a single IV dose of placebo on Day 1.
arm group label: Part 1, Cohort 2: Ketamine Medium Dose
arm group type: Experimental
description: Some participants will be administered a single IV dose of ketamine on Day 1.
arm group label: Part 1, Cohort 2: Placebo
arm group type: Placebo Comparator
description: Some participants will be administered a single IV dose of placebo on Day 1.
arm group label: Part 1, Cohort 3 (Optional): Ketamine High Dose
arm group type: Experimental
description: Optional: some participants will be administered a single IV dose of ketamine on Day 1.
arm group label: Part 1, Cohort 3 (Optional): Placebo
arm group type: Placebo Comparator
description: Optional: some participants will be administered a single IV dose of placebo on Day 1.
arm group label: Part 2, Qualification Phase: Ketamine
arm group type: Experimental
description: Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner.
arm group label: Part 2, Qualification Phase: Placebo
arm group type: Placebo Comparator
description: Participants will receive IV ketamine on Day 2 and placebo on Day 1 in a randomized crossover manner.
arm group label: Part 2, Treatment Phase: Rapastinel Low Dose
arm group type: Experimental
description: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 2, Treatment Phase: Rapastinel Medium Dose
arm group type: Experimental
description: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 2, Treatment Phase: Rapastinel High Dose
arm group type: Experimental
description: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 2, Treatment Phase: Ketamine
arm group type: Active Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 2, Treatment Phase: Placebo
arm group type: Placebo Comparator
description: Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
intervention type: Drug
intervention name: Rapastinel
description: During the Treatment Phase in Part 2, participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 2, Treatment Phase: Rapastinel High Dose
arm group label: Part 2, Treatment Phase: Rapastinel Low Dose
arm group label: Part 2, Treatment Phase: Rapastinel Medium Dose
intervention type: Drug
intervention name: Ketamine
description: Part 1
Part 2, Qualification Phase:
Participants will be administered single IV doses of ketamine and placebo in a randomized crossover manner
Part 2, Treatment Phase:
Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 1, Cohort 1: Ketamine Low Dose
arm group label: Part 1, Cohort 2: Ketamine Medium Dose
arm group label: Part 1, Cohort 3 (Optional): Ketamine High Dose
arm group label: Part 2, Qualification Phase: Ketamine
arm group label: Part 2, Treatment Phase: Ketamine
intervention type: Drug
intervention name: Placebo
description: Part 1
Part 2, Qualification Phase:
Participants will be administered single IV doses of ketamine and placebo in a randomized crossover manner
Part 2, Treatment Phase:
Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner.
arm group label: Part 1, Cohort 1: Placebo
arm group label: Part 1, Cohort 2: Placebo
arm group label: Part 1, Cohort 3 (Optional): Placebo
arm group label: Part 2, Qualification Phase: Placebo
arm group label: Part 2, Treatment Phase: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sheng Fang Su
role: Study Director
affiliation: Allergan
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ketamine
sharing ipd: Undecided