<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/NCT02197884</url>
  </required_header>
  <id_info>
    <org_study_id>CR104763</org_study_id>
    <secondary_id>2014-001793-33</secondary_id>
    <secondary_id>54861911ALZ1009</secondary_id>
    <nct_id>NCT02197884</nct_id>
  </id_info>
  <brief_title>A Study to Assess Effects of Clarithromycin on Pharmacokinetics of JNJ-54861911 in Healthy Male Participants</brief_title>
  <official_title>An Open-Label, Fixed-Sequence Study to Assess Effects of Clarithromycin on the Single-Dose Pharmacokinetics of JNJ-54861911 in Healthy Male 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effects of strong cytochrome P450 (CYP) 3A4&#xD;
      inhibitors (Itraconazole and Clarithromycin), on pharmacokinetics (PK) (study of the way a&#xD;
      drug enters and leaves the blood and tissues over time) of single dose of JNJ-54861911 in&#xD;
      healthy male participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, open-label (participants and researchers are aware about the&#xD;
      treatment, participants are receiving), fixed-sequence study in healthy male participants&#xD;
      consisting of 2 sequential parts. For all participants enrolled in either part, the study&#xD;
      consists of 3 phases: Screening Phase (within 21 to 2 days prior to the first dose&#xD;
      administration on Day 1), Open-label Treatment Phase (Day 1 up to Day 12), and Follow-up&#xD;
      Phase (7 to 14 days after last dose administration). The maximum duration of study will be 7&#xD;
      weeks per participant. Study will be conducted in 2 parts to understand the relative role of&#xD;
      CYP3A4 and amide hydrolysis pathways in JNJ-54861911 metabolism and any potential drug-drug&#xD;
      interaction liability with inhibitors of these pathways. Itraconazole will be administered in&#xD;
      Part 1 as mixed CYP3A4 and potential amide hydrolysis inhibitor. Clarithromycin will be&#xD;
      administered in Part 2 as a pure CYP3A4 inhibitor. However, Part 2 of the study will only be&#xD;
      conducted if a relevant interaction is observed with itraconazole based on an interim review&#xD;
      of Part 1 data. Participants enrolled in Part 1 will receive single dose of JNJ-54861911, 25&#xD;
      milligram (mg) tablet orally on Day 1 and Day 9 along with itraconazole 200 mg (2*100 mg&#xD;
      capsule) orally once daily from Day 5 to Day 12. Participants enrolled in Part 2 will receive&#xD;
      single dose of JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9 along with clarithromycin&#xD;
      500 mg immediate release tablet orally twice daily from Day 5 to Day 12. Blood samples will&#xD;
      be collected pre-dose (Day 1) up to Day 13 to understand the PK characteristics of&#xD;
      JNJ-54861911 and diaminothiazine (DIAT, a metabolite formed after amide hydrolysis of&#xD;
      JNJ-54861911). In addition, a blood sample will be collected on Day -1 from all enrolled&#xD;
      participants to study genotyping of CYP3A4 gene and other genetic factors that may influence&#xD;
      the PK, safety, and/or tolerability of JNJ-54861911 and CYP3A4 inhibitors. Participants'&#xD;
      safety will be monitored throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of JNJ-54861911 and diaminothiazine (DIAT)</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>The Cmax is the maximum observed plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Reach Maximum Concentration (Tmax) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>The Tmax is time to reach the maximum observed plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Last Quantifiable Plasma Concentration (Tlast) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>The Tlast is time to last observed quantifiable plasma concentration (Clast).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-infinity]) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUC (0-last) and Clast/lambda(z), where AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to Time 24 Hours (AUC [0-24]) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to time 24 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Half-Life (t1/2) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, is calculated as 0.693 divided by lambda(z), where lambda(z) is first-order rate constant associated with the terminal portion of the curve. The t1/2 is the measure of time, for plasma concentration to decrease by one half.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Rate Constant (lambda[z]) of JNJ-54861911 and DIAT</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9</time_frame>
    <description>Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)</measure>
    <time_frame>Screening up to follow-up (7 to 14 days after last dose administration)</time_frame>
    <description>An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; and congenital anomaly.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Itraconazole + JNJ-54861911 (Part 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of JNJ-54861911, 25 milligram (mg) tablet orally on Day 1 and Day 9 along with itraconazole 200 mg (2*100 mg capsule) orally once daily from Day 5 to Day 12.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clarithromycin + JNJ-54861911 (Part 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9 along with clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-54861911, 25 mg</intervention_name>
    <description>JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9.</description>
    <arm_group_label>Clarithromycin + JNJ-54861911 (Part 2)</arm_group_label>
    <arm_group_label>Itraconazole + JNJ-54861911 (Part 1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole 200 mg</intervention_name>
    <description>Itraconazole 200 mg (2*100 mg capsule) orally once daily from Day 5 to Day 12.</description>
    <arm_group_label>Itraconazole + JNJ-54861911 (Part 1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clarithromycin 500 mg</intervention_name>
    <description>Clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12.</description>
    <arm_group_label>Clarithromycin + JNJ-54861911 (Part 2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed an informed consent document indicating they understand the purpose of and&#xD;
             procedures required for the study, and are willing to participate in the study&#xD;
&#xD;
          -  Body mass index between 18 and 30 kilogram per square meter&#xD;
&#xD;
          -  Must be healthy on the basis of physical examination, medical history, vital signs,&#xD;
             and 12-lead electrocardiogram (ECG) performed at Screening or admission (up to Day 1&#xD;
             predose)&#xD;
&#xD;
          -  Man, who is sexually active with a woman of child-bearing potential and has not had a&#xD;
             vasectomy, must agree to use an adequate contraception method as deemed appropriate by&#xD;
             the investigator, and must also agree to not donate sperm during the study and for 90&#xD;
             days after receiving the study drug&#xD;
&#xD;
          -  Participant must be healthy on the basis of clinical laboratory tests performed at&#xD;
             Screening and/or admission and as per investigator's judgment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of or current liver or renal impairment, significant cardiac, vascular,&#xD;
             pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic,&#xD;
             psychiatric, dermatological or metabolic disturbances&#xD;
&#xD;
          -  Known allergies, hypersensitivity, or intolerance to JNJ-54861911 or its excipients,&#xD;
             itraconazole (Part 1 only) or clarithromycin (Part 2 only)&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV) antibody positive, or tests positive for&#xD;
             HIV at Screening&#xD;
&#xD;
          -  History of drug or alcohol abuse within 6 months before Screening or positive test&#xD;
             result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine,&#xD;
             cannabinoids, amphetamines, benzodiazepines and cotinine) at Screening or admission&#xD;
&#xD;
          -  Smoking of cigarettes (or equivalent) and/or used nicotine based products within 3&#xD;
             months prior to study drug administration&#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>Merksem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>October 13, 2014</last_update_submitted>
  <last_update_submitted_qc>October 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy</keyword>
  <keyword>JNJ-54861911</keyword>
  <keyword>Cytochrome P450 3A4 inhibitor</keyword>
  <keyword>Itraconazole</keyword>
  <keyword>Clarithromycin</keyword>
  <keyword>Alzheimer's disease</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clarithromycin</mesh_term>
    <mesh_term>Itraconazole</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/NCT02197884
org study id: CR104763
secondary id: 2014-001793-33
secondary id: 54861911ALZ1009
nct id: NCT02197884
lead sponsor: 
has dmc: No
The purpose of this study is to assess the effects of strong cytochrome P450 (CYP) 3A4
      inhibitors (Itraconazole and Clarithromycin), on pharmacokinetics (PK) (study of the way a
      drug enters and leaves the blood and tissues over time) of single dose of JNJ-54861911 in
      healthy male participants.
This is a single-center, open-label (participants and researchers are aware about the
      treatment, participants are receiving), fixed-sequence study in healthy male participants
      consisting of 2 sequential parts. For all participants enrolled in either part, the study
      consists of 3 phases: Screening Phase (within 21 to 2 days prior to the first dose
      administration on Day 1), Open-label Treatment Phase (Day 1 up to Day 12), and Follow-up
      Phase (7 to 14 days after last dose administration). The maximum duration of study will be 7
      weeks per participant. Study will be conducted in 2 parts to understand the relative role of
      CYP3A4 and amide hydrolysis pathways in JNJ-54861911 metabolism and any potential drug-drug
      interaction liability with inhibitors of these pathways. Itraconazole will be administered in
      Part 1 as mixed CYP3A4 and potential amide hydrolysis inhibitor. Clarithromycin will be
      administered in Part 2 as a pure CYP3A4 inhibitor. However, Part 2 of the study will only be
      conducted if a relevant interaction is observed with itraconazole based on an interim review
      of Part 1 data. Participants enrolled in Part 1 will receive single dose of JNJ-54861911, 25
      milligram (mg) tablet orally on Day 1 and Day 9 along with itraconazole 200 mg (2*100 mg
      capsule) orally once daily from Day 5 to Day 12. Participants enrolled in Part 2 will receive
      single dose of JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9 along with clarithromycin
      500 mg immediate release tablet orally twice daily from Day 5 to Day 12. Blood samples will
      be collected pre-dose (Day 1) up to Day 13 to understand the PK characteristics of
      JNJ-54861911 and diaminothiazine (DIAT, a metabolite formed after amide hydrolysis of
      JNJ-54861911). In addition, a blood sample will be collected on Day -1 from all enrolled
      participants to study genotyping of CYP3A4 gene and other genetic factors that may influence
      the PK, safety, and/or tolerability of JNJ-54861911 and CYP3A4 inhibitors. Participants'
      safety will be monitored throughout the study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-54861911 and diaminothiazine (DIAT)
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: The Cmax is the maximum observed plasma concentration.
measure: Time to Reach Maximum Concentration (Tmax) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: The Tmax is time to reach the maximum observed plasma concentration.
measure: Time to Last Quantifiable Plasma Concentration (Tlast) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: The Tlast is time to last observed quantifiable plasma concentration (Clast).
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-infinity]) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUC (0-last) and Clast/lambda(z), where AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time 24 Hours (AUC [0-24]) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: Area under the plasma concentration-time curve from time zero to time 24 hours.
measure: Elimination Half-Life (t1/2) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, is calculated as 0.693 divided by lambda(z), where lambda(z) is first-order rate constant associated with the terminal portion of the curve. The t1/2 is the measure of time, for plasma concentration to decrease by one half.
measure: Elimination Rate Constant (lambda[z]) of JNJ-54861911 and DIAT
time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9
description: Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
time frame: Screening up to follow-up (7 to 14 days after last dose administration)
description: An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; and congenital anomaly.
arm group label: Itraconazole + JNJ-54861911 (Part 1)
arm group type: Experimental
description: Single dose of JNJ-54861911, 25 milligram (mg) tablet orally on Day 1 and Day 9 along with itraconazole 200 mg (2*100 mg capsule) orally once daily from Day 5 to Day 12.
arm group label: Clarithromycin + JNJ-54861911 (Part 2)
arm group type: Experimental
description: Single dose of JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9 along with clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12.
intervention type: Drug
intervention name: JNJ-54861911, 25 mg
description: JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9.
arm group label: Clarithromycin + JNJ-54861911 (Part 2)
arm group label: Itraconazole + JNJ-54861911 (Part 1)
intervention type: Drug
intervention name: Itraconazole 200 mg
description: Itraconazole 200 mg (2*100 mg capsule) orally once daily from Day 5 to Day 12.
arm group label: Itraconazole + JNJ-54861911 (Part 1)
intervention type: Drug
intervention name: Clarithromycin 500 mg
description: Clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12.
arm group label: Clarithromycin + JNJ-54861911 (Part 2)
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: Belgium
responsible party type: Sponsor
mesh term: Clarithromycin
mesh term: Itraconazole