<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/NCT03808259</url>
  </required_header>
  <id_info>
    <org_study_id>CR108553</org_study_id>
    <secondary_id>2018-003435-30</secondary_id>
    <secondary_id>54135419EDI1001</secondary_id>
    <nct_id>NCT03808259</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Different Modes of (S) Ketamine Administration in Healthy Participants</brief_title>
  <official_title>A Randomized, Participant- and Investigator Blind, Double Dummy, Placebo- and Comparator-controlled, Single Ascending Dose and Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Different Modes of (S) Ketamine Administration in Healthy Participants</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>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK) and&#xD;
      pharmacodynamics (PD) of different modes of (S) ketamine administration in healthy&#xD;
      participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2018</start_date>
  <completion_date type="Actual">September 4, 2019</completion_date>
  <primary_completion_date type="Actual">September 4, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) Total Score</measure>
    <time_frame>Baseline up to Day 1</time_frame>
    <description>CADSS is an instrument for the measurement of present-state dissociative symptoms and will be administered to assess treatment-emergent dissociative symptoms. CADSS consists of 23 subjective items, divided into 3 components: depersonalization (items 3 to 7, 20, and 23), derealization (items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (items 14, 15, and 22). The participants responses are coded on a 5-point scale (from 0=not at all to 4=extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Change from Baseline in CADSS Total Score</measure>
    <time_frame>Baseline up to Day 1</time_frame>
    <description>CADSS is an instrument for the measurement of present-state dissociative symptoms and will be administered to assess treatment-emergent dissociative symptoms. CADSS consists of 23 subjective items, divided into 3 components: depersonalization (items 3 to 7, 20, and 23), derealization (items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (items 14, 15, and 22). The participants responses are coded on a 5-point scale (from 0=not at all to 4=extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Number of Participants with Vital Sign Abnormalities</measure>
    <time_frame>Up to Day 2</time_frame>
    <description>Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Number of Participants with Vital Sign Abnormalities</measure>
    <time_frame>Up to Day 2</time_frame>
    <description>Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Concentrations of (S)-ketamine</measure>
    <time_frame>Part 1: Predose, 1, 3, 5, 10, 15, 30, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hour postdose; Part 2: predose, 15, 30 min, 1, 1.6, 2, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours postdose</time_frame>
    <description>Observed plasma concentrations of (S)-ketamine will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Concentrations of Nor(S)-ketamine</measure>
    <time_frame>Part 1: Predose, 1, 3, 5, 10, 15, 30, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hour postdose; Part 2: predose, 15, 30 min, 1, 1.6, 2, 3, 3.5, 4, 6, 8, 10, 12 and 24 hours postdose</time_frame>
    <description>Observed plasma concentrations of Nor(S)-ketamine will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Change from Baseline in Electroencephalogram (EEG) Power</measure>
    <time_frame>Predose (Baseline) and 2.25 hours postdose</time_frame>
    <description>EEG power spectral activity in the alpha 1, alpha 2, beta 1, beta 2, delta, theta and gamma frequency bands will be estimated for the baseline EEG recording and will be compared to the EEG power spectral activity in the same frequency bands.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Change from Baseline in EEG Power</measure>
    <time_frame>Predose (Baseline) and 3.25 hours postdose</time_frame>
    <description>EEG power spectral activity in the alpha 1, alpha 2, beta 1, beta 2, delta, theta and gamma frequency bands will be estimated for the baseline EEG recording and will be compared to the EEG power spectral activity in the same frequency bands.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Change from Baseline in Continuous Paired Associate Learning Test (cPALT) Score</measure>
    <time_frame>Baseline up to Day 1</time_frame>
    <description>The cPALT will be used to assess whether drug will improve performance of complex cognitive tasks. CPAL assesses Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In participants, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. The outcome is number of errors made in correctly placing each of the four patterns in their location four times (Lower score = better performance).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Change from Baseline in cPALT Score</measure>
    <time_frame>Baseline up to Day 1</time_frame>
    <description>The cPALT will be used to assess whether drug will improve performance of complex cognitive tasks. CPAL assesses Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In participants, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. The outcome is number of errors made in correctly placing each of the four patterns in their location four times (Lower score = better performance).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">96</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Part 1: OTF Sublingual and IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive (S)-ketamine oral thin film (OTF) at a dose of 7 milligram (mg) [cohort 1], 14 mg [cohort 2], and 28 mg [cohort 3] via sublingual route or 14 mg (S)-ketamine intravenous (IV) infusion for 40 minutes or matching placebo in 1 of 3 serial cohorts. Dose escalation decisions to further cohorts of Part 1 will be made based on safety and tolerability profile of the preceding lower dose level.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: IV Different Infusion Duration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive single dose (S)-ketamine less than or equal to (&lt;=)14 mg IV at a different infusion duration or matching placebo at a different infusion duration. The infusion duration and dose will be chosen after completion of Part 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>(S)-ketamine Oral Thin Film</intervention_name>
    <description>(S)-ketamine OTF sublingual formulation at a dose of 7 mg, 14 mg, and 28 mg will be administered in sequential cohorts.</description>
    <arm_group_label>Part 1: OTF Sublingual and IV</arm_group_label>
    <other_name>JNJ-54135419</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>(S)-ketamine IV Infusion</intervention_name>
    <description>(S)-ketamine IV solution will be infused at a dose of less than or equal to 14mg.</description>
    <arm_group_label>Part 1: OTF Sublingual and IV</arm_group_label>
    <arm_group_label>Part 2: IV Different Infusion Duration</arm_group_label>
    <other_name>Ketanest</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive matching placebo.</description>
    <arm_group_label>Part 1: OTF Sublingual and IV</arm_group_label>
    <arm_group_label>Part 2: IV Different Infusion Duration</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body Mass Index (BMI) between 20 and 28 kilogram per meter square (kg/m^2), inclusive&#xD;
             (BMI=weight/height^2) with a minimum weight of 60 kilogram (kg) and a maximum of 100&#xD;
             kg&#xD;
&#xD;
          -  Participant must be healthy based on clinical laboratory tests performed at screening.&#xD;
             If the results of the serum chemistry panel, hematology or urinalysis are outside the&#xD;
             normal reference ranges, retesting of an abnormal lab value(s) that may lead to&#xD;
             exclusion will be allowed once during the screening phase&#xD;
&#xD;
          -  Participant must be healthy based on physical and neurological examination, medical&#xD;
             history, vital signs, and 12-lead electrocardiogram (ECG) (including QT corrected&#xD;
             according to Fridericia's formula [QTcF] less than or equal to [&lt;=] 450 milliseconds&#xD;
             [msec] for males and &lt;= 470 msec for females) performed at screening. Abnormalities,&#xD;
             which are not considered to be of clinical significance by the Investigator, are&#xD;
             acceptable. The presence of left bundle branch block (LBBB), atrioventricular (AV)&#xD;
             Block (second degree or higher), or a permanent pacemaker or implantable cardioverter&#xD;
             defibrillator (ICD) will lead to exclusion&#xD;
&#xD;
          -  Participant must have systolic blood pressure (SBP) and heart rate (HR) within normal&#xD;
             limits at screening and at Day -1: supine SBP of at least 90 millimeters of mercury&#xD;
             (mmHg) and maximum 150mmHg, supine diastolic blood pressure (DBP) should be above&#xD;
             50mmHg and below 90mmHg and the HR must be between 45 beats per minute (BPM) and 100&#xD;
             BPM. If the results are outside the normal reference ranges above, retesting will be&#xD;
             allowed once during the screening phase&#xD;
&#xD;
          -  Non-smoker (not smoked for 3 months prior to screening)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiac arrhythmias or other cardiac disease, hematological disease, hypertension,&#xD;
             lipid abnormalities, respiratory disease, diabetes mellitus, renal or hepatic&#xD;
             insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness&#xD;
             that the Investigator considers should exclude the participant&#xD;
&#xD;
          -  Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies&#xD;
             or human immunodeficiency virus (HIV) antibodies at screening visit&#xD;
&#xD;
          -  Participant has a history of drug or alcohol use disorder or psychiatric disorder&#xD;
             according to Diagnostic and Statistical Manual of Mental Disorders (5th edition)&#xD;
             (DSM-V) criteria within 6 months before screening (for example psychotic, bipolar,&#xD;
             major depressive, or anxiety disorder) or positive test result(s) for alcohol and/or&#xD;
             drugs of abuse (opiates (including methadone), cocaine, amphetamines,&#xD;
             methamphetamines, cannabinoids, barbiturates, ecstasy and benzodiazepines) at&#xD;
             screening or admission&#xD;
&#xD;
          -  Drinks, on average, more than 8 cups of tea/coffee/cocoa/cola per day&#xD;
&#xD;
          -  Clinically significant acute illness within 7 days prior to study drug administration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 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>Clinical Pharmacology Unit</name>
      <address>
        <city>Merksem</city>
        <zip>2170</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>September 10, 2019</last_update_submitted>
  <last_update_submitted_qc>September 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 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>Esketamine</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/NCT03808259
org study id: CR108553
secondary id: 2018-003435-30
secondary id: 54135419EDI1001
nct id: NCT03808259
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK) and
      pharmacodynamics (PD) of different modes of (S) ketamine administration in healthy
      participants.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Part 1: Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) Total Score
time frame: Baseline up to Day 1
description: CADSS is an instrument for the measurement of present-state dissociative symptoms and will be administered to assess treatment-emergent dissociative symptoms. CADSS consists of 23 subjective items, divided into 3 components: depersonalization (items 3 to 7, 20, and 23), derealization (items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (items 14, 15, and 22). The participants responses are coded on a 5-point scale (from 0=not at all to 4=extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.
measure: Part 2: Change from Baseline in CADSS Total Score
time frame: Baseline up to Day 1
description: CADSS is an instrument for the measurement of present-state dissociative symptoms and will be administered to assess treatment-emergent dissociative symptoms. CADSS consists of 23 subjective items, divided into 3 components: depersonalization (items 3 to 7, 20, and 23), derealization (items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (items 14, 15, and 22). The participants responses are coded on a 5-point scale (from 0=not at all to 4=extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.
measure: Part 1: Number of Participants with Vital Sign Abnormalities
time frame: Up to Day 2
description: Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.
measure: Part 2: Number of Participants with Vital Sign Abnormalities
time frame: Up to Day 2
description: Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.
measure: Plasma Concentrations of (S)-ketamine
time frame: Part 1: Predose, 1, 3, 5, 10, 15, 30, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hour postdose; Part 2: predose, 15, 30 min, 1, 1.6, 2, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours postdose
description: Observed plasma concentrations of (S)-ketamine will be reported.
measure: Plasma Concentrations of Nor(S)-ketamine
time frame: Part 1: Predose, 1, 3, 5, 10, 15, 30, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hour postdose; Part 2: predose, 15, 30 min, 1, 1.6, 2, 3, 3.5, 4, 6, 8, 10, 12 and 24 hours postdose
description: Observed plasma concentrations of Nor(S)-ketamine will be reported.
measure: Part 1: Change from Baseline in Electroencephalogram (EEG) Power
time frame: Predose (Baseline) and 2.25 hours postdose
description: EEG power spectral activity in the alpha 1, alpha 2, beta 1, beta 2, delta, theta and gamma frequency bands will be estimated for the baseline EEG recording and will be compared to the EEG power spectral activity in the same frequency bands.
measure: Part 2: Change from Baseline in EEG Power
time frame: Predose (Baseline) and 3.25 hours postdose
description: EEG power spectral activity in the alpha 1, alpha 2, beta 1, beta 2, delta, theta and gamma frequency bands will be estimated for the baseline EEG recording and will be compared to the EEG power spectral activity in the same frequency bands.
measure: Part 1: Change from Baseline in Continuous Paired Associate Learning Test (cPALT) Score
time frame: Baseline up to Day 1
description: The cPALT will be used to assess whether drug will improve performance of complex cognitive tasks. CPAL assesses Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In participants, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. The outcome is number of errors made in correctly placing each of the four patterns in their location four times (Lower score = better performance).
measure: Part 2: Change from Baseline in cPALT Score
time frame: Baseline up to Day 1
description: The cPALT will be used to assess whether drug will improve performance of complex cognitive tasks. CPAL assesses Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In participants, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. The outcome is number of errors made in correctly placing each of the four patterns in their location four times (Lower score = better performance).
arm group label: Part 1: OTF Sublingual and IV
arm group type: Experimental
description: Participants will receive (S)-ketamine oral thin film (OTF) at a dose of 7 milligram (mg) [cohort 1], 14 mg [cohort 2], and 28 mg [cohort 3] via sublingual route or 14 mg (S)-ketamine intravenous (IV) infusion for 40 minutes or matching placebo in 1 of 3 serial cohorts. Dose escalation decisions to further cohorts of Part 1 will be made based on safety and tolerability profile of the preceding lower dose level.
arm group label: Part 2: IV Different Infusion Duration
arm group type: Experimental
description: Participants will receive single dose (S)-ketamine less than or equal to (<=)14 mg IV at a different infusion duration or matching placebo at a different infusion duration. The infusion duration and dose will be chosen after completion of Part 1.
intervention type: Drug
intervention name: (S)-ketamine Oral Thin Film
description: (S)-ketamine OTF sublingual formulation at a dose of 7 mg, 14 mg, and 28 mg will be administered in sequential cohorts.
arm group label: Part 1: OTF Sublingual and IV
other name: JNJ-54135419
intervention type: Drug
intervention name: (S)-ketamine IV Infusion
description: (S)-ketamine IV solution will be infused at a dose of less than or equal to 14mg.
arm group label: Part 1: OTF Sublingual and IV
arm group label: Part 2: IV Different Infusion Duration
other name: Ketanest
intervention type: Drug
intervention name: Placebo
description: Participants will receive matching placebo.
arm group label: Part 1: OTF Sublingual and IV
arm group label: Part 2: IV Different Infusion Duration
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Ketamine
mesh term: Esketamine
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