<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/NCT03007693</url>
  </required_header>
  <id_info>
    <org_study_id>CR108250</org_study_id>
    <secondary_id>2016-003894-16</secondary_id>
    <secondary_id>61393215EDI1002</secondary_id>
    <nct_id>NCT03007693</nct_id>
  </id_info>
  <brief_title>A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ 61393215 in Healthy Participants</brief_title>
  <official_title>A Randomized, Placebo-controlled, Double-blind, Multiple Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ 61393215 in Healthy Subjects</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>
    <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 investigate the safety and tolerability of JNJ-61393215 after&#xD;
      multiple consecutive dose administrations and to characterize the pharmacokinetics (PK) of&#xD;
      JNJ-61393215 in plasma after multiple consecutive dose administrations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">October 2017</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>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Treatment Emergent Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>up to 4 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time To Reach The Maximum Plasma Concentration (Tmax)</measure>
    <time_frame>Day 1</time_frame>
    <description>Tmax is time to reach the maximum plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>Day 1</time_frame>
    <description>Cmax is maximum plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time [0 to24] (AUC[0-24])</measure>
    <time_frame>Day 1</time_frame>
    <description>AUC[0-24] is area under the plasma concentration- time curve from time [0 to 24].</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Observed Plasma Concentration Just Prior To the Beginning or at the End of a Dosing Interval of any Dose Other Than the First Dose (Ctrough)</measure>
    <time_frame>Days 2 to 6</time_frame>
    <description>Ctrough is the observed plasma concentration just prior to the beginning or at the end of a dosing interval of any dose other than the first dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Observed Plasma Concentration Just Prior To the Beginning or at the End of a Dosing Interval of any Dose Other Than the First Dose (Ctrough)</measure>
    <time_frame>Day 7</time_frame>
    <description>Ctrough is the observed plasma concentration just prior to the beginning or at the end of a dosing interval of any dose other than the first dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Minimum Observed Plasma Concentration During Dosing Interval (tau) (Cmin)</measure>
    <time_frame>Day 7</time_frame>
    <description>Cmin is minimum observed plasma concentration during dosing interval (tau).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time To Reach The Maximum Plasma Concentration (Tmax)</measure>
    <time_frame>Day 7</time_frame>
    <description>Tmax is time to reach the maximum plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>Day 7</time_frame>
    <description>Cmax is maximum plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time [0 to24] (AUC[0-24])</measure>
    <time_frame>Day 7</time_frame>
    <description>AUC[0-24] is Area under the plasma concentration- time curve from time [0 to 24].</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Average Plasma Concentration at Steady State Over the Dosing Interval (Cavg)</measure>
    <time_frame>Day 7</time_frame>
    <description>Cavg is average plasma concentration at steady state over the dosing interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fluctuation Index (FI)</measure>
    <time_frame>Day 7</time_frame>
    <description>Fluctuation Index is defined as percentage of fluctuation, calculated as: 100*([Cmax-Cmin]/Cavg).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Apparent Oral Clearance, Calculated as Dose/AUCtau at Steady-State (CL/F)</measure>
    <time_frame>Day 7</time_frame>
    <description>CL/F is total apparent oral clearance, calculated as dose/AUCtau at steady-state.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Rate Constant, Determined By Linear Regression of the Terminal Points of the Ln-Linear Plasma Concentration-Time Curve (Lambda[Z])</measure>
    <time_frame>Day 7</time_frame>
    <description>Lambda[Z] is apparent terminal elimination rate constant, determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Elimination Half-Life Associated With The Terminal Slope of The Semilogarithmic Drug Concentration-Time Curve, After Multiple-Dose Administration Only (t1/2term)</measure>
    <time_frame>Day 7</time_frame>
    <description>T1/2term is apparent elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, after multiple-dose administration only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of Maximum Plasma Concentration (Cmax) Test (Day 7 [steady-state]/ref (Day 1) (Ratio Cmax,test/ref)</measure>
    <time_frame>Day 7</time_frame>
    <description>Ratio Cmax,test/ref is ratio of maximum plasma concentration (Cmax) test (day 7 [steady-state]/ref (day 1).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of Area Under the Plasma Concentration-Time Curve From Time [0 to24] (AUC[0-24]) Test (Day 7 [steady-state]/ref (Day 1) (Ratio AUC24h,test/ref)</measure>
    <time_frame>Day 7</time_frame>
    <description>Ratio AUC24h,test/ref is ratio of area under the plasma concentration- time curve from time [0 to 24] (AUC[0-24]) test (day 7 [steady-state]/ref (day 1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of JNJ-61393215 on Alertness/Sedation Through the Bond &amp; Lader Visual Analogue Scale</measure>
    <time_frame>Day 1 and Day 7</time_frame>
    <description>Visual Analogue Scale (VAS) is made up of 16 pairs of alternative descriptors of mood and attention at either end. The Bond-Lader of a 10 cm line. Participants will rate their feelings at the time of assessment by indicating the point on the line which best represent their mood. Each item is scored by measuring the position relative to the left hand end of the line and levels of anxiety, sedation, and dysphoria are then calculated from the combined scores of selected items. The score ranges from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>JNJ-61393215 (Multiple Ascending Dose Phase)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive JNJ- 61393215 once daily for 7 days. 4 sequential cohorts will be enrolled to evaluate escalating doses which will be defined, based on safety, tolerability and pharmacokinetic (PK) data from the preceding cohorts. Dose adjustment/selection (increase/decrease) for the next cohort will be based on the JNJ- 61393215 PK profile up to and including the last day of dosing (24 hours postdose) and the safety and tolerability profile of the current cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Multiple Ascending Dose Phase)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive JNJ- 61393215 matching placebo for 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-61393215</intervention_name>
    <description>Participants will receive JNJ-61393215 for 7 days.</description>
    <arm_group_label>JNJ-61393215 (Multiple Ascending Dose Phase)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive JNJ- 61393215 matching placebo for 7 days.</description>
    <arm_group_label>Placebo (Multiple Ascending Dose Phase)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male participants between 18 and 55 years of age, inclusive&#xD;
&#xD;
          -  Participants must have a body mass index (BMI) between 18.0 and 30.0 kilogram per&#xD;
             square meter (kg/m^2), inclusive (BMI = weight/height square)&#xD;
&#xD;
          -  Participant must be healthy on the basis of physical examination, medical history,&#xD;
             vital signs, and 12-lead ECG [incl. QTcF less than or equal to [&lt;=] 450 milliseconds&#xD;
             (msec) for males] performed at screening and admission to the clinical unit. Minor&#xD;
             abnormalities in electrocardiogram (ECG), which are not considered to be of clinical&#xD;
             significance by the investigator, are acceptable. The presence of Left Bundle Branch&#xD;
             Block (LBBB), AV Block (second degree or higher), or a permanent pacemaker or&#xD;
             implantable cardioverter defibrillator [ICD] will lead to exclusion&#xD;
&#xD;
          -  Participants must be healthy on the basis of clinical laboratory tests performed at&#xD;
             screening. If the results of the serum chemistry panel, hematology, or urinalysis are&#xD;
             outside the normal reference ranges, the Participant may be included only if the&#xD;
             investigator judges the abnormalities to be not clinically significant. This&#xD;
             determination must be recorded in the Participant's source documents and initialed by&#xD;
             the investigator&#xD;
&#xD;
          -  A man who is sexually active with a woman of childbearing potential and has not had a&#xD;
             vasectomy must agree to use a barrier method of contraception e.g., either condom with&#xD;
             spermicidal foam/gel/film/cream/suppository during the study and for a minimum of 1&#xD;
             spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose&#xD;
             of study drug. All men must also not donate sperm during the study and for 3 months&#xD;
             after receiving the last dose of study drug. In addition, their female partner should&#xD;
             also use a highly effective method of contraception for at least the same duration.&#xD;
             Examples of highly effective contraceptives include implantable progestogen-only&#xD;
             hormone contraception associated with inhibition of ovulation; intrauterine device&#xD;
             (IUD); intrauterine hormone-releasing system (IUS); vasectomized partner; sexual&#xD;
             abstinence (sexual abstinence is considered a highly effective method only if defined&#xD;
             as refraining from heterosexual intercourse during the entire period of risk&#xD;
             associated with the study drug. The reliability of sexual abstinence needs to be&#xD;
             evaluated in relation to the duration of the study and the preferred and usual&#xD;
             lifestyle of the participant.), combined (estrogen- and progestogen-containing)&#xD;
             hormonal contraception associated with inhibition of ovulation: oral, intravaginal,&#xD;
             and transdermal; progestogen-only hormone contraception associated with inhibition of&#xD;
             ovulation: oral and injectable.&#xD;
&#xD;
          -  Participants must be willing to adhere to the prohibitions and restrictions specified&#xD;
             in this protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has a history of or current liver or renal insufficiency; significant&#xD;
             cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic,&#xD;
             rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any&#xD;
             other illness, though minor deviations, which are not considered to be of clinical&#xD;
             significance to both the investigator and to the Janssen Safety Responsible Physician,&#xD;
             are acceptable&#xD;
&#xD;
          -  Current or past history of any psychiatric disorder as classified according to&#xD;
             Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) or DSM-V, with the&#xD;
             exclusion of an anxiety disorder (i.e., panic disorder with or without agoraphobia,&#xD;
             social anxiety disorder, and generalized anxiety disorder)&#xD;
&#xD;
          -  Participant has any liver function test (including alanine aminotransferase [ALT],&#xD;
             aspartate aminotransferase [AST], gamma-glutamyltransferase [gGT], alkaline&#xD;
             phosphatase [ALP and bilirubin] at screening exceeding the upper limit of normal&#xD;
&#xD;
          -  Participant has estimated glomerular filtration rate (eGFR) &lt;60 milliliter per minute&#xD;
             (mL/min)/1.73m^2 at screening (provided by the local laboratory)&#xD;
&#xD;
          -  Participant has a heart rate &lt; 50 beats per minute (bpm) or &gt; 100 bpm or systolic&#xD;
             blood pressure greater than or equal to (&gt;=) 150 millimeter of mercury (mmHg) at&#xD;
             screening or at admission to the clinical unit&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>December 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>November 17, 2017</last_update_submitted>
  <last_update_submitted_qc>November 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03007693
org study id: CR108250
secondary id: 2016-003894-16
secondary id: 61393215EDI1002
nct id: NCT03007693
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the safety and tolerability of JNJ-61393215 after
      multiple consecutive dose administrations and to characterize the pharmacokinetics (PK) of
      JNJ-61393215 in plasma after multiple consecutive dose administrations.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Number of Participants with Treatment Emergent Adverse Events as a Measure of Safety and Tolerability
time frame: up to 4 weeks
measure: Time To Reach The Maximum Plasma Concentration (Tmax)
time frame: Day 1
description: Tmax is time to reach the maximum plasma concentration.
measure: Maximum Plasma Concentration (Cmax)
time frame: Day 1
description: Cmax is maximum plasma concentration.
measure: Area Under the Plasma Concentration-Time Curve From Time [0 to24] (AUC[0-24])
time frame: Day 1
description: AUC[0-24] is area under the plasma concentration- time curve from time [0 to 24].
measure: The Observed Plasma Concentration Just Prior To the Beginning or at the End of a Dosing Interval of any Dose Other Than the First Dose (Ctrough)
time frame: Days 2 to 6
description: Ctrough is the observed plasma concentration just prior to the beginning or at the end of a dosing interval of any dose other than the first dose.
measure: The Observed Plasma Concentration Just Prior To the Beginning or at the End of a Dosing Interval of any Dose Other Than the First Dose (Ctrough)
time frame: Day 7
description: Ctrough is the observed plasma concentration just prior to the beginning or at the end of a dosing interval of any dose other than the first dose.
measure: Minimum Observed Plasma Concentration During Dosing Interval (tau) (Cmin)
time frame: Day 7
description: Cmin is minimum observed plasma concentration during dosing interval (tau).
measure: Time To Reach The Maximum Plasma Concentration (Tmax)
time frame: Day 7
description: Tmax is time to reach the maximum plasma concentration.
measure: Maximum Plasma Concentration (Cmax)
time frame: Day 7
description: Cmax is maximum plasma concentration.
measure: Area Under the Plasma Concentration-Time Curve From Time [0 to24] (AUC[0-24])
time frame: Day 7
description: AUC[0-24] is Area under the plasma concentration- time curve from time [0 to 24].
measure: Average Plasma Concentration at Steady State Over the Dosing Interval (Cavg)
time frame: Day 7
description: Cavg is average plasma concentration at steady state over the dosing interval.
measure: Fluctuation Index (FI)
time frame: Day 7
description: Fluctuation Index is defined as percentage of fluctuation, calculated as: 100*([Cmax-Cmin]/Cavg).
measure: Total Apparent Oral Clearance, Calculated as Dose/AUCtau at Steady-State (CL/F)
time frame: Day 7
description: CL/F is total apparent oral clearance, calculated as dose/AUCtau at steady-state.
measure: Apparent Terminal Elimination Rate Constant, Determined By Linear Regression of the Terminal Points of the Ln-Linear Plasma Concentration-Time Curve (Lambda[Z])
time frame: Day 7
description: Lambda[Z] is apparent terminal elimination rate constant, determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.
measure: Apparent Elimination Half-Life Associated With The Terminal Slope of The Semilogarithmic Drug Concentration-Time Curve, After Multiple-Dose Administration Only (t1/2term)
time frame: Day 7
description: T1/2term is apparent elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, after multiple-dose administration only.
measure: Ratio of Maximum Plasma Concentration (Cmax) Test (Day 7 [steady-state]/ref (Day 1) (Ratio Cmax,test/ref)
time frame: Day 7
description: Ratio Cmax,test/ref is ratio of maximum plasma concentration (Cmax) test (day 7 [steady-state]/ref (day 1).
measure: Ratio of Area Under the Plasma Concentration-Time Curve From Time [0 to24] (AUC[0-24]) Test (Day 7 [steady-state]/ref (Day 1) (Ratio AUC24h,test/ref)
time frame: Day 7
description: Ratio AUC24h,test/ref is ratio of area under the plasma concentration- time curve from time [0 to 24] (AUC[0-24]) test (day 7 [steady-state]/ref (day 1).
measure: Effect of JNJ-61393215 on Alertness/Sedation Through the Bond & Lader Visual Analogue Scale
time frame: Day 1 and Day 7
description: Visual Analogue Scale (VAS) is made up of 16 pairs of alternative descriptors of mood and attention at either end. The Bond-Lader of a 10 cm line. Participants will rate their feelings at the time of assessment by indicating the point on the line which best represent their mood. Each item is scored by measuring the position relative to the left hand end of the line and levels of anxiety, sedation, and dysphoria are then calculated from the combined scores of selected items. The score ranges from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.
arm group label: JNJ-61393215 (Multiple Ascending Dose Phase)
arm group type: Experimental
description: Participants will receive JNJ- 61393215 once daily for 7 days. 4 sequential cohorts will be enrolled to evaluate escalating doses which will be defined, based on safety, tolerability and pharmacokinetic (PK) data from the preceding cohorts. Dose adjustment/selection (increase/decrease) for the next cohort will be based on the JNJ- 61393215 PK profile up to and including the last day of dosing (24 hours postdose) and the safety and tolerability profile of the current cohort.
arm group label: Placebo (Multiple Ascending Dose Phase)
arm group type: Placebo Comparator
description: Participants will receive JNJ- 61393215 matching placebo for 7 days.
intervention type: Drug
intervention name: JNJ-61393215
description: Participants will receive JNJ-61393215 for 7 days.
arm group label: JNJ-61393215 (Multiple Ascending Dose Phase)
intervention type: Drug
intervention name: Placebo
description: Participants will receive JNJ- 61393215 matching placebo for 7 days.
arm group label: Placebo (Multiple Ascending Dose Phase)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: Netherlands
responsible party type: Sponsor