<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/NCT03032367</url>
  </required_header>
  <id_info>
    <org_study_id>TASK-002</org_study_id>
    <nct_id>NCT03032367</nct_id>
  </id_info>
  <brief_title>TASK-002: Bioequivalence of Bedaquiline 400mg Administered in Crushed Form Compared to Tablet Form in Healthy Male and Female Adults Under Fed Conditions (BDQ Crush Study)</brief_title>
  <official_title>TASK-002: Bioequivalence of Bedaquiline 400mg Administered in Crushed Form Compared to Tablet Form in Healthy Male and Female Adults Under Fed Conditions (BDQ Crush Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Maternal Pediatric Adolescent AIDS Clinical Trials Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>US National Institute of Allergy and Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>International Maternal Pediatric Adolescent AIDS Clinical Trials Group</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, open-label, cross-over study comparing the bioequivalence of&#xD;
      bedaquiline administered in whole tablet form versus bedaquiline administered in crushed&#xD;
      (experimental) form in healthy adult volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, cross-over, bioequivalence study with two single treatment&#xD;
      periods, separated by a 14-day wash-out period, conducted among 24 healthy adult males and&#xD;
      females, who receive 400mg (4 x 100mg) bedaquiline orally in one of two sequences: either&#xD;
      first in whole tablet form and second in crushed (experimental) form, or vice versa under fed&#xD;
      conditions. The bioequivalence evaluation will be based on primary pharmacokinetic (pk)&#xD;
      parameters affecting the extent of absorption, i.e., the bioavailability. If bioequivalence&#xD;
      is not shown, the knowledge about the differences in bioavailability between whole and&#xD;
      crushed tablets will be used for assessing the need of dose adjustment in children receiving&#xD;
      the crushed form.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 10, 2016</start_date>
  <completion_date type="Actual">January 11, 2017</completion_date>
  <primary_completion_date type="Actual">December 9, 2016</primary_completion_date>
  <phase>Early 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>
    <intervention_model_description>Participants are randomized to receive study drug (bedaquiline (BDQ)) in either tablet form or crushed form in one of two sequences:&#xD;
Sequence 1: BDQ 4 x 100mg administered in a whole tablet form, followed by BDQ 4 x 100mg administered in crushed form as a once only dose&#xD;
Sequence 2: BDQ 4 x 100mg administered in crushed form, followed by BDQ 4 x 100mg administered in tablet form as a once only dose</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bioequivalence of bedaquiline 4 x 100mg given to healthy adult males and females orally in tablet form compared to crushed form</measure>
    <time_frame>Two single treatment sequences, separated by a 14-day wash-out period</time_frame>
    <description>The bioequivalence evaluation will be based on primary PK parameters affecting the extent of absorption, i.e. the bioavailability.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Sequence 1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Bedaquiline 4 x 100mg administered in a whole tablet form, followed by bedaquiline 4 x 100mg administered in crushed form as a once only oral dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Bedaquiline 4x 100mg administered in crushed form, followed by bedaquiline 4 x 100mg administered in a whole tablet form, as a once only oral dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bedaquiline</intervention_name>
    <arm_group_label>Sequence 1</arm_group_label>
    <arm_group_label>Sequence 2</arm_group_label>
    <other_name>Sirturo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent, including HIV testing&#xD;
&#xD;
          -  Male or female between 18 and 55 years of age inclusive&#xD;
&#xD;
          -  Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive&#xD;
&#xD;
          -  In the opinion of the investigator, able to comply with the requirements of the&#xD;
             protocol e.g. able to attend all visits for PK analysis&#xD;
&#xD;
          -  Be of non-childbearing potential or using effective methods of birth control&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or suspected hypersensitivity or intolerance to bedaquiline or any other&#xD;
             constituents of the study drug, i.e. lactose&#xD;
&#xD;
          -  A history or clinical evidence of any clinically significant cardiac condition&#xD;
             including but not limited to congenital long QT syndrome, Torsades de Pointes,&#xD;
             bradyarrhythmias&#xD;
&#xD;
          -  Uncontrolled cardiac dysrhythmias&#xD;
&#xD;
          -  Severe hepatic impairment (Child Pugh C)&#xD;
&#xD;
          -  History, symptoms or signs of heart failure&#xD;
&#xD;
          -  History, symptoms or signs of hypothyroidism, whether currently controlled or&#xD;
             uncontrolled&#xD;
&#xD;
          -  Any other serious uncontrolled medical condition or clinically significant&#xD;
             abnormality, which, in the opinion of the investigator, might compromise the safety of&#xD;
             the subject or which might interfere with the study.&#xD;
&#xD;
          -  Evidence of clinically significant (as judged by the investigator), metabolic,&#xD;
             gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary,&#xD;
             neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities.&#xD;
&#xD;
          -  Concomitant use of medicines known to prolong the QTc interval, or use of CYP3A4&#xD;
             inducers/inhibitors including but not limited to, carbamazepine, phenytoin, St. John's&#xD;
             wort, ciprofloxacin, erythromycin, clarithromycin, fluconazole, ketoconazole,&#xD;
             ritonavir or other anti-retroviral medications, fluoroquinolones and clofazamine.&#xD;
&#xD;
          -  HIV positive, already known or as per HIV test done at screening.&#xD;
&#xD;
          -  Hepatitis B or C positive&#xD;
&#xD;
          -  QTc prolongation as per ECG with a QTcF of &gt;450msec or any other significant finding&#xD;
             on the ECG as per the investigator&#xD;
&#xD;
          -  Receipt of any study drug within the past 3 months.&#xD;
&#xD;
          -  Scheduled to receive any other investigational drug during the course of the study.&#xD;
&#xD;
          -  Known or suspected, current or history of within the past 2 years, alcohol or drug&#xD;
             abuse, that is, in the opinion of the Investigator, sufficient to compromise the&#xD;
             safety or cooperation of the volunteer.&#xD;
&#xD;
          -  Evidence or suspicion of active TB or documented recent (within the last year)&#xD;
             household contact with an infectious TB case.&#xD;
&#xD;
          -  The following toxicities at screening as defined by the DAIDS toxicity table (November&#xD;
             2014)&#xD;
&#xD;
               1. aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN)&#xD;
&#xD;
               2. alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN)&#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>Jeannine du Bois, MD</last_name>
    <role>Study Chair</role>
    <affiliation>TASK Clinical Research Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anthony Garcia-Pratts, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Desmond Tutu TB Centre, Stellenbosch University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>TASK Clinical Research Centre</name>
      <address>
        <city>Bellville</city>
        <state>Western Cape</state>
        <zip>7530</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>July 26, 2017</last_update_submitted>
  <last_update_submitted_qc>July 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bedaquiline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03032367
org study id: TASK-002
nct id: NCT03032367
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a randomized, open-label, cross-over study comparing the bioequivalence of
      bedaquiline administered in whole tablet form versus bedaquiline administered in crushed
      (experimental) form in healthy adult volunteers.
This is a randomized, open-label, cross-over, bioequivalence study with two single treatment
      periods, separated by a 14-day wash-out period, conducted among 24 healthy adult males and
      females, who receive 400mg (4 x 100mg) bedaquiline orally in one of two sequences: either
      first in whole tablet form and second in crushed (experimental) form, or vice versa under fed
      conditions. The bioequivalence evaluation will be based on primary pharmacokinetic (pk)
      parameters affecting the extent of absorption, i.e., the bioavailability. If bioequivalence
      is not shown, the knowledge about the differences in bioavailability between whole and
      crushed tablets will be used for assessing the need of dose adjustment in children receiving
      the crushed form.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Participants are randomized to receive study drug (bedaquiline (BDQ)) in either tablet form or crushed form in one of two sequences:
Sequence 1: BDQ 4 x 100mg administered in a whole tablet form, followed by BDQ 4 x 100mg administered in crushed form as a once only dose
Sequence 2: BDQ 4 x 100mg administered in crushed form, followed by BDQ 4 x 100mg administered in tablet form as a once only dose
primary purpose: Other
masking: None (Open Label)
measure: Bioequivalence of bedaquiline 4 x 100mg given to healthy adult males and females orally in tablet form compared to crushed form
time frame: Two single treatment sequences, separated by a 14-day wash-out period
description: The bioequivalence evaluation will be based on primary PK parameters affecting the extent of absorption, i.e. the bioavailability.
arm group label: Sequence 1
arm group type: Other
description: Bedaquiline 4 x 100mg administered in a whole tablet form, followed by bedaquiline 4 x 100mg administered in crushed form as a once only oral dose
arm group label: Sequence 2
arm group type: Other
description: Bedaquiline 4x 100mg administered in crushed form, followed by bedaquiline 4 x 100mg administered in a whole tablet form, as a once only oral dose
intervention type: Drug
intervention name: bedaquiline
arm group label: Sequence 1
arm group label: Sequence 2
other name: Sirturo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeannine du Bois, MD
role: Study Chair
affiliation: TASK Clinical Research Centre
last name: Anthony Garcia-Pratts, MD
role: Study Chair
affiliation: Desmond Tutu TB Centre, Stellenbosch University
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Bedaquiline
sharing ipd: No