<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/NCT03800550</url>
  </required_header>
  <id_info>
    <org_study_id>CR108570</org_study_id>
    <secondary_id>2018-004302-25</secondary_id>
    <secondary_id>TMC207NTM1001</secondary_id>
    <nct_id>NCT03800550</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Participants</brief_title>
  <official_title>A Phase 1, Open-label, Randomized, Crossover Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Volunteers</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 assess the effect of steady-state clarithromycin once every&#xD;
      12 hour on the pharmacokinetic parameters of bedaquiline and its active metabolite M2 after a&#xD;
      single dose of bedaquiline.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 13, 2019</start_date>
  <completion_date type="Actual">June 4, 2019</completion_date>
  <primary_completion_date type="Actual">June 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>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Analyte Concentration (Cmax) of Bedaquiline and its Metabolite (M2)</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose</time_frame>
    <description>Cmax is the maximum observed analyte concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Minimum Observed Analyte Concentration (Cmin) of Bedaquiline and its Metabolite (M2)</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose</time_frame>
    <description>Cmin is the minimum observed analyte concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 72 Hours Post Dosing (AUC72h) of Bedaquiline and its Metabolite (M2)</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours Post-dose</time_frame>
    <description>AUC72h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 72 hours post dosing, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 240 Hours Post Dosing (AUC240h) of Bedaquiline and its Metabolite (M2)</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose</time_frame>
    <description>AUC240h is the area under the analyte concentration-time curve from time 0 to 240 hours, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax of Clarithromycin and its Metabolite 14-OH-Clarithromycin</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose</time_frame>
    <description>Cmax is the maximum observed analyte concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Analyte Concentration (Tmax) of Clarithromycin and its Metabolite 14-OH-Clarithromycin</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose</time_frame>
    <description>Tmax is the actual sampling time to reach the maximum observed analyte concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin of Clarithromycin and its Metabolite 14-OH-Clarithromycin</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose</time_frame>
    <description>Cmin is the minimum observed analyte concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of Clarithromycin and its Metabolite 14-OH-Clarithromycin</measure>
    <time_frame>Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose</time_frame>
    <description>AUC12h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 12 hours post dosing, calculated by linear-linear trapezoidal summation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 90 days</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment Sequence 1: Bedaquiline and Clarithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive bedaquiline on Day 1 in Period 1, followed by clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 2. There will be washout period of at least 28 days starting on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence 2: Clarithromycin and Bedaquiline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 1, followed by bedaquiline on Day 1 in Period 2. There will be a washout period of at least 28 days starting after bedaquiline administration on Day 5.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bedaquiline</intervention_name>
    <description>Bedaquiline tablet will be administered, orally.</description>
    <arm_group_label>Treatment Sequence 1: Bedaquiline and Clarithromycin</arm_group_label>
    <arm_group_label>Treatment Sequence 2: Clarithromycin and Bedaquiline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clarithromycin</intervention_name>
    <description>Clarithromycin tablet will be administered, orally.</description>
    <arm_group_label>Treatment Sequence 1: Bedaquiline and Clarithromycin</arm_group_label>
    <arm_group_label>Treatment Sequence 2: Clarithromycin and Bedaquiline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A female participant must have a negative highly sensitive serum (beta-human chorionic&#xD;
             gonadotropin [beta-hCG]) pregnancy test at screening and on Day -1 in each treatment&#xD;
             period&#xD;
&#xD;
          -  Contraceptive use by women should be consistent with local regulations regarding the&#xD;
             use of contraceptive methods for participants participating in clinical studies&#xD;
&#xD;
          -  A female participant must agree not to donate eggs (ova, oocytes) for the purposes of&#xD;
             assisted reproduction during the study and for at least 90 days after receiving the&#xD;
             last dose of bedaquiline&#xD;
&#xD;
          -  During the study and for a minimum of at least 90 days after receiving the last dose&#xD;
             of bedaquiline: a) A male participant must wear a condom when engaging in any activity&#xD;
             that allows for passage of ejaculate to another person (male participants should also&#xD;
             be advised of the benefit for a female partner to use a highly effective method of&#xD;
             contraception as condom may break or leak. b) A male participant must agree not to&#xD;
             donate sperm for the purpose of reproduction&#xD;
&#xD;
          -  Body mass index (BMI between 18.0 and 30.0 kilogram (kg) per meter square (inclusive),&#xD;
             and body weight not less than 50 kg at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has history or current clinically significant medical illness including&#xD;
             (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic&#xD;
             disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias),&#xD;
             lipid abnormalities, significant pulmonary disease (including bronchospastic&#xD;
             respiratory disease), diabetes mellitus, hepatic or renal insufficiency (for example,&#xD;
             estimated creatinine clearance below 60 milliliter per minute [mL/min] at screening),&#xD;
             gastrointestinal disease (such as significant diarrhea, gastric stasis, or&#xD;
             constipation that in the investigator's opinion could influence drug absorption or&#xD;
             bioavailability), thyroid disease, neurologic or psychiatric disease, infection, or&#xD;
             any other illness that the investigator considers should exclude the participant or&#xD;
             that could interfere with the interpretation of the study results&#xD;
&#xD;
          -  Participant with a past history of heart arrhythmias (extrasystoles or tachycardia at&#xD;
             rest), or history of risk factors for Torsade de Pointes syndrome (for example,&#xD;
             hypokalemia, or family history of long QT syndrome). Family history of sudden&#xD;
             unexplained death (including sudden infant death syndrome in a first-degree relative&#xD;
             (that is, sibling, offspring, or biological parent). Ongoing bradyarrhythmias or&#xD;
             ongoing hypothyroidism (confirmed by elevated thyroid-stimulating hormone [TSH] level)&#xD;
&#xD;
          -  Participant with any history of clinically significant skin disease such as, but not&#xD;
             limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria&#xD;
&#xD;
          -  Participant has taken any disallowed therapies before the planned first intake of&#xD;
             study drug&#xD;
&#xD;
          -  Participant has a history of drug or alcohol abuse according to Diagnostic and&#xD;
             Statistical Manual of Mental Disorders (5th edition) criteria within 5 years before&#xD;
             screening or positive test result(s) for alcohol and/or drugs of abuse (including&#xD;
             barbiturates, opiates, cocaine, amphetamines, methadone, benzodiazepines,&#xD;
             methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants)&#xD;
             at screening and on Day 1 of each treatment period&#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>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>SGS Life Science Services</name>
      <address>
        <city>Antwerpen</city>
        <zip>2060</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>August 26, 2019</last_update_submitted>
  <last_update_submitted_qc>August 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 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>Clarithromycin</mesh_term>
    <mesh_term>Bedaquiline</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. 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/NCT03800550
org study id: CR108570
secondary id: 2018-004302-25
secondary id: TMC207NTM1001
nct id: NCT03800550
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to assess the effect of steady-state clarithromycin once every
      12 hour on the pharmacokinetic parameters of bedaquiline and its active metabolite M2 after a
      single dose of bedaquiline.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Maximum Observed Analyte Concentration (Cmax) of Bedaquiline and its Metabolite (M2)
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
description: Cmax is the maximum observed analyte concentration.
measure: Minimum Observed Analyte Concentration (Cmin) of Bedaquiline and its Metabolite (M2)
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
description: Cmin is the minimum observed analyte concentration.
measure: Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 72 Hours Post Dosing (AUC72h) of Bedaquiline and its Metabolite (M2)
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours Post-dose
description: AUC72h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 72 hours post dosing, calculated by linear-linear trapezoidal summation.
measure: Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 240 Hours Post Dosing (AUC240h) of Bedaquiline and its Metabolite (M2)
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
description: AUC240h is the area under the analyte concentration-time curve from time 0 to 240 hours, calculated by linear-linear trapezoidal summation.
measure: Cmax of Clarithromycin and its Metabolite 14-OH-Clarithromycin
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
description: Cmax is the maximum observed analyte concentration.
measure: Time to Reach Maximum Observed Analyte Concentration (Tmax) of Clarithromycin and its Metabolite 14-OH-Clarithromycin
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
description: Tmax is the actual sampling time to reach the maximum observed analyte concentration.
measure: Cmin of Clarithromycin and its Metabolite 14-OH-Clarithromycin
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
description: Cmin is the minimum observed analyte concentration.
measure: Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of Clarithromycin and its Metabolite 14-OH-Clarithromycin
time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose
description: AUC12h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 12 hours post dosing, calculated by linear-linear trapezoidal summation.
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Up to 90 days
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
arm group label: Treatment Sequence 1: Bedaquiline and Clarithromycin
arm group type: Experimental
description: Participants will receive bedaquiline on Day 1 in Period 1, followed by clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 2. There will be washout period of at least 28 days starting on Day 1.
arm group label: Treatment Sequence 2: Clarithromycin and Bedaquiline
arm group type: Experimental
description: Participants will receive clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 1, followed by bedaquiline on Day 1 in Period 2. There will be a washout period of at least 28 days starting after bedaquiline administration on Day 5.
intervention type: Drug
intervention name: Bedaquiline
description: Bedaquiline tablet will be administered, orally.
arm group label: Treatment Sequence 1: Bedaquiline and Clarithromycin
arm group label: Treatment Sequence 2: Clarithromycin and Bedaquiline
intervention type: Drug
intervention name: Clarithromycin
description: Clarithromycin tablet will be administered, orally.
arm group label: Treatment Sequence 1: Bedaquiline and Clarithromycin
arm group label: Treatment Sequence 2: Clarithromycin and Bedaquiline
criteria: 
gender: All
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: Bedaquiline
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