<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/NCT03298906</url>
  </required_header>
  <id_info>
    <org_study_id>CR108377</org_study_id>
    <secondary_id>54135419TRD1020</secondary_id>
    <secondary_id>2017-003174-14</secondary_id>
    <nct_id>NCT03298906</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Effect of Ticlopidine on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants</brief_title>
  <official_title>A Fixed-sequence, Open-label Study to Assess the Effect of Ticlopidine on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine 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>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effects of ticlopidine on the pharmacokinetics&#xD;
      (PK) of intranasally administered esketamine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Actual">November 27, 2017</completion_date>
  <primary_completion_date type="Actual">November 27, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Esketamine</measure>
    <time_frame>Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose</time_frame>
    <description>The Cmax is the maximum observed plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Esketamine</measure>
    <time_frame>Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is area under the plasma concentration time curve from time zero to last quantifiable time; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to time of Last Quantifiable Concentration (AUC [0-last]) of Esketamine</measure>
    <time_frame>Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose</time_frame>
    <description>The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable concentration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs) as a measure of Safety and Tolerability</measure>
    <time_frame>From signing of the informed consent form (ICF) onwards until the participant's last study-related activity (Approximately up to 8 weeks)</time_frame>
    <description>An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Esketamine + Ticlopidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will self-administer one 14 milligram (mg) spray of intranasal esketamine into each nostril at Time 0 and again 5 minutes later on Day 1, a total dose of 56 mg (Treatment A) in Treatment Period 1. After that participants will receive 250 mg of ticlopidine tablets orally twice daily on Day -9 through Day 1, and will self-administer one 14 mg spray of intranasal esketamine into each nostril at Time 0 and again 5 minutes later in the morning of Day 1, a total dose of 56 mg (Treatment B) in Treatment Period 2. A washout period of greater than or equal to (&gt;=)10 days will separate the esketamine self-administrations between 2 treatment periods.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>Participants will self-administer one intranasal spray of 14 mg esketamine at Time 0 and again 5 minutes later on Day 1, a total dose of 56 mg in Treatment Period 1 and 2.</description>
    <arm_group_label>Esketamine + Ticlopidine</arm_group_label>
    <other_name>JNJ-54135419</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticlopidine</intervention_name>
    <description>Participants will receive 250 mg ticlopidine tablets orally twice daily on Day -9 through Day 1 in Treatment Period 2.</description>
    <arm_group_label>Esketamine + Ticlopidine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be healthy on the basis of physical examination, medical history, vital signs, and&#xD;
             12-lead electrocardiogram (ECG) performed at screening&#xD;
&#xD;
          -  A woman must be either:&#xD;
&#xD;
               1. Not of childbearing potential defined as:&#xD;
&#xD;
                    1. postmenopausal (it is defined as no menses for 12 months without an&#xD;
                       alternative medical cause. A high follicle stimulating hormone [FSH] level&#xD;
                       [greater than {&gt;}40 International Unit per Liter {IU/L} or&#xD;
                       milliinternational Unit per milliliter {mIU/mL}] in the postmenopausal range&#xD;
                       may be used to confirm a postmenopausal state in women not using hormonal&#xD;
                       contraception or hormonal replacement therapy, however in the absence of 12&#xD;
                       months of amenorrhea, a single FSH measurement is insufficient)&#xD;
&#xD;
                    2. permanently sterile (permanent sterilization methods include hysterectomy,&#xD;
                       bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and&#xD;
                       bilateral oophorectomy)&#xD;
&#xD;
               2. Of childbearing potential, heterosexually active, and&#xD;
&#xD;
                    1. practicing a highly effective method of contraception (failure rate of less&#xD;
                       than [&lt;]1 percent [%] per year when used consistently and correctly)&#xD;
&#xD;
                    2. agree to remain on a highly effective method throughout the study and for at&#xD;
                       least 6 weeks after the last dose of study drug&#xD;
&#xD;
          -  For women, must have a negative serum Beta- human chorionic gonadotropin (Beta-hCG)&#xD;
             pregnancy test at screening&#xD;
&#xD;
          -  During the study and for a minimum of 1 spermatogenesis cycle (defined as&#xD;
             approximately 90 days) after receiving the last dose of intranasal study medication, a&#xD;
             man who is sexually active with a woman of childbearing potential&#xD;
&#xD;
               1. must be practicing a highly effective method of contraception with his female&#xD;
                  partner&#xD;
&#xD;
               2. must use a condom if his partner is pregnant, and&#xD;
&#xD;
               3. must agree not to donate sperm&#xD;
&#xD;
          -  Have a creatinine clearance greater than or equal to (&gt;=) 60 milliliter per minute&#xD;
             (mL/min) (calculated using the Cockcroft-Gault formula) at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a current significant psychiatric disorder including but not limited to psychotic,&#xD;
             bipolar, major depressive, or anxiety disorder&#xD;
&#xD;
          -  Has a clinically significant medical illness including (but not limited to) cardiac&#xD;
             arrhythmias or other cardiac disease, hematologic disease, coagulation disorders&#xD;
             (including any abnormal bleeding or blood dyscrasias), lipid abnormalities,&#xD;
             significant pulmonary disease, including bronchospastic respiratory disease, diabetes&#xD;
             mellitus, renal or hepatic insufficiency, thyroid disease, neurologic disease,&#xD;
             infection, hypertension or vascular disorders, kidney or urinary tract disturbances,&#xD;
             sleep apnea, myasthenia gravis, or any other illness that the investigator considers&#xD;
             should exclude the participant or that could interfere with the interpretation of the&#xD;
             study results. Participants with medical conditions that are stable with treatment may&#xD;
             be included and should be discussed with the medical monitor before inclusion&#xD;
&#xD;
          -  Has clinically significant abnormal values for hematology, serum chemistry, or&#xD;
             urinalysis at screening as deemed appropriate by the investigator&#xD;
&#xD;
          -  Has any contraindication to the use of ticlopidine, ketamine, or esketamine per&#xD;
             prescribing information&#xD;
&#xD;
          -  Has a history of human immunodeficiency virus (HIV) antibody positive, or tests&#xD;
             positive for HIV at screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>58 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>December 2017</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>December 18, 2017</last_update_submitted>
  <last_update_submitted_qc>December 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2017</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>Ticlopidine</mesh_term>
    <mesh_term>Esketamine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03298906
org study id: CR108377
secondary id: 54135419TRD1020
secondary id: 2017-003174-14
nct id: NCT03298906
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate the effects of ticlopidine on the pharmacokinetics
      (PK) of intranasally administered esketamine.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax) of Esketamine
time frame: Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose
description: The Cmax is the maximum observed plasma concentration.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Esketamine
time frame: Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose
description: The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is area under the plasma concentration time curve from time zero to last quantifiable time; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to time of Last Quantifiable Concentration (AUC [0-last]) of Esketamine
time frame: Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose
description: The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable concentration.
measure: Number of Participants with Adverse Events (AEs) as a measure of Safety and Tolerability
time frame: From signing of the informed consent form (ICF) onwards until the participant's last study-related activity (Approximately up to 8 weeks)
description: An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
arm group label: Esketamine + Ticlopidine
arm group type: Experimental
description: Participants will self-administer one 14 milligram (mg) spray of intranasal esketamine into each nostril at Time 0 and again 5 minutes later on Day 1, a total dose of 56 mg (Treatment A) in Treatment Period 1. After that participants will receive 250 mg of ticlopidine tablets orally twice daily on Day -9 through Day 1, and will self-administer one 14 mg spray of intranasal esketamine into each nostril at Time 0 and again 5 minutes later in the morning of Day 1, a total dose of 56 mg (Treatment B) in Treatment Period 2. A washout period of greater than or equal to (>=)10 days will separate the esketamine self-administrations between 2 treatment periods.
intervention type: Drug
intervention name: Esketamine
description: Participants will self-administer one intranasal spray of 14 mg esketamine at Time 0 and again 5 minutes later on Day 1, a total dose of 56 mg in Treatment Period 1 and 2.
arm group label: Esketamine + Ticlopidine
other name: JNJ-54135419
intervention type: Drug
intervention name: Ticlopidine
description: Participants will receive 250 mg ticlopidine tablets orally twice daily on Day -9 through Day 1 in Treatment Period 2.
arm group label: Esketamine + Ticlopidine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 58 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: Ticlopidine
mesh term: Esketamine