<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/NCT01691534</url>
  </required_header>
  <id_info>
    <org_study_id>NC-003-(C-J-Pa-Z)</org_study_id>
    <nct_id>NCT01691534</nct_id>
  </id_info>
  <brief_title>Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z)</brief_title>
  <acronym>NC-003</acronym>
  <official_title>A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of the Following: TMC207 Plus PA-824 Plus Pyrazinamide Plus Clofazimine, TMC207 Plus PA-824 Plus Pyrazinamide, TMC207 Plus PA-824 Plus Clofazimine Alone, TMC207 Plus Pyrazinamide Plus Clofazimine, Pyrazinamide Alone, and Clofazimine Alone; in Adult Patients With Newly Diagnosed, Smear-Positive Pulmonary Tuberculosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Global Alliance for TB Drug Development</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Global Alliance for TB Drug Development</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral&#xD;
      administration of TMC207 plus PA-824 plus Pyrazinamide plus Clofazimine, TMC207 plus PA-824&#xD;
      plus Pyrazinamide, TMC207 plus PA-824 plus Clofazimine alone, TMC207 plus Pyrazinamide plus&#xD;
      Clofazimine, Pyrazinamide alone, Clofazimine alone, and standard first line TB treatment as&#xD;
      per South African TB Guidelines (Rifafour e-275) as determined by the rate of change of log&#xD;
      CFU per ml sputum over the time period Day 0-14 in participants with smear positive pulmonary&#xD;
      tuberculosis (TB). A control group will receive standard treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">April 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-14).</measure>
    <time_frame>14 consecutive days of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 0-2)</measure>
    <time_frame>Days 0-2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 7-14)</measure>
    <time_frame>Day 7-14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EBA Expressed as the Daily Percentage Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)</measure>
    <time_frame>Days 0-14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Day 0-2)</measure>
    <time_frame>Day 0-2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Days 7-14)</measure>
    <time_frame>Days 7-14</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">105</enrollment>
  <condition>Pulmonary Tuberculosis</condition>
  <arm_group>
    <arm_group_label>TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus PA-824 200mg Days 1-14 plus pyrazinamide 1500mg Days 1-14 plus clofazimine 300mg Days 1-3 and Clofazamine 100mg Days 4-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMC207, PA-824 and pyrazinamide (J-PA-Z)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus PA-824 200mg Days 1-14 plus pyrazinamide 1500mg Days 1-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMC207, PA-824 and clofazimine (J-PA-C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus PA-824 200mg Days 1-14 plus clofazimine 300mg Days 1-3 and clofazimine 100mg Days 4-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMC207, pyrazinamide and clofazimine (J-Z-C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus pyrazinamide 1500mg Days 1-14 plus clofazimine 300mg Days 1-3 and Clofazimine 100mg Days 4-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>pyrazinamide (Z)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pyrazinamide 1500mg Days 1-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>clofazimine (C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Clofazimine 300mg Days 1-3 and Clofazimine 100mg Days 4-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rifafour</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Rifafour e-275 mg dosed by weight</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMC207 (J)</intervention_name>
    <description>TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14</description>
    <arm_group_label>TMC207, PA-824 and clofazimine (J-PA-C)</arm_group_label>
    <arm_group_label>TMC207, PA-824 and pyrazinamide (J-PA-Z)</arm_group_label>
    <arm_group_label>TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)</arm_group_label>
    <arm_group_label>TMC207, pyrazinamide and clofazimine (J-Z-C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PA-824 (PA)</intervention_name>
    <description>PA-824 200mg Days 1-14</description>
    <arm_group_label>TMC207, PA-824 and clofazimine (J-PA-C)</arm_group_label>
    <arm_group_label>TMC207, PA-824 and pyrazinamide (J-PA-Z)</arm_group_label>
    <arm_group_label>TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pyrazinamide (Z)</intervention_name>
    <description>1500mg Days 1-14 Dosed by Weight</description>
    <arm_group_label>TMC207, PA-824 and pyrazinamide (J-PA-Z)</arm_group_label>
    <arm_group_label>TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)</arm_group_label>
    <arm_group_label>TMC207, pyrazinamide and clofazimine (J-Z-C)</arm_group_label>
    <arm_group_label>pyrazinamide (Z)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>clofazimine (C)</intervention_name>
    <description>clofazimine 300mg Days 1-3 and clofazimine 100mg Days 4-14</description>
    <arm_group_label>TMC207, PA-824 and clofazimine (J-PA-C)</arm_group_label>
    <arm_group_label>TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)</arm_group_label>
    <arm_group_label>TMC207, pyrazinamide and clofazimine (J-Z-C)</arm_group_label>
    <arm_group_label>clofazimine (C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifafour</intervention_name>
    <description>Rifafour e-275 mg dosed by weight</description>
    <arm_group_label>Rifafour</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Provide written, informed consent prior to all trial-related procedures including&#xD;
             HIV testing.&#xD;
&#xD;
             2. Male or female, aged between 18 and 65 years inclusive.&#xD;
&#xD;
             3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.&#xD;
&#xD;
             4. Newly diagnosed, previously untreated, sputum smear-positive pulmonary TB.&#xD;
&#xD;
             5. A chest X-ray picture which in the opinion of the Investigator is compatible with&#xD;
             TB.&#xD;
&#xD;
             6. Sputum positive GeneXpert or TB Smear from TB clinic or site initial diagnosis&#xD;
&#xD;
             7. Sputum positive on direct microscopy for acid-fast bacilli (at least 1+ on the&#xD;
             IUATLD/WHO scale).&#xD;
&#xD;
             8. Ability to produce an adequate volume of sputum as estimated from a spot assessment&#xD;
             (estimated 10 ml or more overnight production).&#xD;
&#xD;
             9. Be of non-childbearing potential or using an effective method of birth control as&#xD;
             defined as:&#xD;
&#xD;
        Non-childbearing potential:&#xD;
&#xD;
          1. Subject - Not heterosexually active or practice sexual abstinence or&#xD;
&#xD;
          2. Female subject/sexual bilateral oophorectomy, bilateral tubal ligation, and/or&#xD;
             hysterectomy or has been postmenopausal with a history of no menses for at least 12&#xD;
             consecutive months) or&#xD;
&#xD;
          3. Male subject/sexual partner - vasectomised or has had a bilateral orchidectomy&#xD;
             minimally three month prior to screening&#xD;
&#xD;
        Effective birth control methods:&#xD;
&#xD;
          1. Double barrier method which can include a male condom, diaphragms, cervical cap, or&#xD;
             female condom or&#xD;
&#xD;
          2. Barrier method combined with hormone based contraceptives or an intra-uterine device&#xD;
             for the female partner and are willing to continue practicing birth control methods&#xD;
             throughout treatment and for 12 weeks (male participants) or 6 months (female&#xD;
             participants) after the last dose of study medication or discontinuation from study&#xD;
             medication in case of premature discontinuation&#xD;
&#xD;
        (Note: Hormone-based contraception alone may not be reliable when taking IMP; therefore,&#xD;
        hormone-based contraceptives alone cannot be used by female participants to prevent&#xD;
        pregnancy).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. 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;
             (other than the indication being studied) including malaria.&#xD;
&#xD;
          2. Poor general condition where any delay in treatment cannot be tolerated per discretion&#xD;
             of the Investigator.&#xD;
&#xD;
          3. A history of previous TB.&#xD;
&#xD;
          4. Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB,&#xD;
             urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.&#xD;
&#xD;
          5. History of allergy to the IMP or related substances.&#xD;
&#xD;
          6. Isoniazid-resistant and/or Rifampicin-resistant bacteria detected with a sputum&#xD;
             specimen collected within the pre-treatment period and tested at the study laboratory.&#xD;
&#xD;
          7. 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 participant.&#xD;
&#xD;
          8. HIV infected participants:&#xD;
&#xD;
               1. having a CD4+ count &lt;200 cells/µL;&#xD;
&#xD;
               2. or having received antiretroviral therapy medication within the last 90 days;&#xD;
&#xD;
               3. or having received oral or intravenous antifungal medication within the last 90&#xD;
                  days;&#xD;
&#xD;
               4. or with an AIDS-defining opportunistic infection or malignancies (except&#xD;
                  pulmonary TB).&#xD;
&#xD;
          9. Having participated in other clinical studies with investigational agents within 8&#xD;
             weeks prior to trial start.&#xD;
&#xD;
         10. Significant cardiac arrhythmia requiring medication.&#xD;
&#xD;
         11. Participants with the following at screening. For ECGs, central cardiology overread&#xD;
             and the mean of triplicate reading must be used:&#xD;
&#xD;
               1. Marked prolongation of QT/QTc interval, e.g., confirmed demonstration of QTcF&#xD;
                  (Fridericia correction) or QTcB (Bazett correction) interval &gt;450 ms at&#xD;
                  screening;&#xD;
&#xD;
               2. History of additional risk factors for Torsade de Pointes, e.g., heart failure,&#xD;
                  hypokalemia, family history of Long QT Syndrome;&#xD;
&#xD;
               3. Use of concomitant medications that prolong the QT/QTc interval (see exclusion&#xD;
                  criterion 19 and disallowed medications;&#xD;
&#xD;
               4. Pathological Q waves (defined as &gt;40ms or depth &gt;0.4-0.5mV);&#xD;
&#xD;
               5. ECG evidence of ventricular pre-excitation;&#xD;
&#xD;
               6. ECG evidence of complete or incomplete left bundle branch block or right bundle&#xD;
                  branch block;&#xD;
&#xD;
               7. ECG evidence of second or third degree heart block;&#xD;
&#xD;
               8. Intraventricular conduction delay with QRS duration &gt;120ms;&#xD;
&#xD;
               9. Bradycardia as defined by sinus rate &lt;50bpm.&#xD;
&#xD;
         12. Females who are pregnant, breast-feeding, or planning to conceive a child within 6&#xD;
             months of cessation of treatment. Males planning to conceive a child within twelve&#xD;
             weeks of cessation of treatment.&#xD;
&#xD;
         13. Diabetes Mellitus requiring insulin.&#xD;
&#xD;
         14. History of lens opacity.&#xD;
&#xD;
         15. For males, any history of a clinically significant abnormality in the reproductive&#xD;
             system.&#xD;
&#xD;
             Specific Treatments&#xD;
&#xD;
         16. Previously received treatment with Clofazimine, TMC207 or PA-824.&#xD;
&#xD;
         17. Treatment received with any drug active against MTB within the 3 months prior to Visit&#xD;
             1 (e.g. isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin,&#xD;
             rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine,&#xD;
             pyrazinamide, thioacetazone, capreomycin, thioamides, metronidazole).&#xD;
&#xD;
         18. Any diseases or conditions in which the use of the standard TB drugs or any of their&#xD;
             components is contra-indicated, including but not limited to allergy to any TB drug,&#xD;
             their component or to the IMP.&#xD;
&#xD;
         19. Concomitant use of any drug known to prolong QTc interval (including amiodarone,&#xD;
             bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, cyclobenzaprine,&#xD;
             disopyramide dofetilide, domperidone, droperidol, erythromycin, halofantrine,&#xD;
             haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide,&#xD;
             procainamide, quinidine, sotalol, sparfloxacin, thioridazine).&#xD;
&#xD;
         20. Use of any drugs or substances within 30 days prior to dosing known to be strong&#xD;
             inhibitors or inducers of cytochrome P450 enzymes (such as quinidine, tyramine,&#xD;
             ketoconazole, testosterone, quinine, gestodene, metyrapone, phenelzine, doxorubicin,&#xD;
             troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline, cimetidine,&#xD;
             dextromethorphan). Exceptions may be made for participants that have received 3 days&#xD;
             or less of one of these drugs or substances, if there has been a wash-out period&#xD;
             before administration of IMP equivalent to at least 5 half-lives of that drug or&#xD;
             substance.&#xD;
&#xD;
         21. Use of any therapeutic agents known to alter any major organ function (e.g.,&#xD;
             barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.&#xD;
             Exceptions for opiate and pain killer use for cough or underlying disease may be made&#xD;
             at investigator discretion.&#xD;
&#xD;
             Based on Laboratory Abnormalities&#xD;
&#xD;
         22. Participants with the following toxicities at screening as defined by the enhanced&#xD;
             Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November&#xD;
             2007):&#xD;
&#xD;
               1. creatinine grade 2 or greater (&gt;1.5 times upper limit of normal [ULN]);&#xD;
&#xD;
               2. lipase grade 3 or greater (&gt;2.0 x ULN);&#xD;
&#xD;
               3. hemoglobin grade 4 (&lt;6.5 g/dL);&#xD;
&#xD;
               4. platelets grade 2 or greater (under 50x109 cells/L);&#xD;
&#xD;
               5. serum potassium grade 2 or greater (&lt;3.5 mEq/L);&#xD;
&#xD;
               6. aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN) to be excluded;&#xD;
&#xD;
               7. alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN) to be excluded;&#xD;
&#xD;
               8. alkaline phosphatase (ALP) grade 4 (&gt;8.0 x ULN) to be excluded, grade 3 (≥3.0 x&#xD;
                  ULN) must be discussed with the sponsor Medical Monitor;&#xD;
&#xD;
               9. total bilirubin grade 3 or greater (&gt;2.0 x ULN, or &gt;1.50 x ULN when accompanied&#xD;
                  by any increase in other liver function test) to be excluded, grade 2 (&gt;1.50 x&#xD;
                  ULN, or &gt;1.25 x ULN when accompanied by any increase in other liver function&#xD;
                  test) must be discussed with the sponsor Medical Monitor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andreas Diacon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karl Bremer Hospital, Cape Town South Africa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Tuberculosis Research Innovation, UCT Lung Institute</name>
      <address>
        <city>Cape Town</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Task Applied Science, Karl Bremer Hospita</name>
      <address>
        <city>Cape Town</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <link>
    <url>http://www.tballiance.org/home/home.php</url>
    <description>Sponsor home page</description>
  </link>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <results_first_submitted>October 19, 2016</results_first_submitted>
  <results_first_submitted_qc>October 19, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 13, 2016</results_first_posted>
  <last_update_submitted>October 19, 2016</last_update_submitted>
  <last_update_submitted_qc>October 19, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 13, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tuberculosis</keyword>
  <keyword>EBA</keyword>
  <keyword>PA824</keyword>
  <keyword>pretomanid</keyword>
  <keyword>TMC207</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Tuberculosis, Pulmonary</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pyrazinamide</mesh_term>
    <mesh_term>Clofazimine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="P2">
          <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
        </group>
        <group group_id="P3">
          <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="P4">
          <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="P5">
          <title>Pyrazinamide (Z)</title>
          <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
        </group>
        <group group_id="P6">
          <title>Clofazimine (C)</title>
          <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="P7">
          <title>Rifafour</title>
          <description>Rifafour on Days 1 to 14, dosed by weight</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
                <participants group_id="P5" count="15"/>
                <participants group_id="P6" count="15"/>
                <participants group_id="P7" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="15"/>
                <participants group_id="P6" count="14"/>
                <participants group_id="P7" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="B2">
          <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
        </group>
        <group group_id="B3">
          <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="B4">
          <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="B5">
          <title>Pyrazinamide (Z)</title>
          <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
        </group>
        <group group_id="B6">
          <title>Clofazimine (C)</title>
          <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="B7">
          <title>Rifafour</title>
          <description>Rifafour on Days 1 to 14, dosed by weight</description>
        </group>
        <group group_id="B8">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="15"/>
            <count group_id="B6" value="15"/>
            <count group_id="B7" value="15"/>
            <count group_id="B8" value="105"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.5" spread="8.74"/>
                    <measurement group_id="B2" value="33.4" spread="14.22"/>
                    <measurement group_id="B3" value="33.3" spread="11.15"/>
                    <measurement group_id="B4" value="30.9" spread="13.12"/>
                    <measurement group_id="B5" value="32.4" spread="11.44"/>
                    <measurement group_id="B6" value="28.4" spread="8.77"/>
                    <measurement group_id="B7" value="34.3" spread="10.25"/>
                    <measurement group_id="B8" value="32.6" spread="11.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="8"/>
                    <measurement group_id="B8" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="9"/>
                    <measurement group_id="B6" value="9"/>
                    <measurement group_id="B7" value="7"/>
                    <measurement group_id="B8" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="9"/>
                    <measurement group_id="B8" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mixed Ethnic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="9"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="168.6" spread="7.98"/>
                    <measurement group_id="B2" value="165.3" spread="8.64"/>
                    <measurement group_id="B3" value="166.8" spread="11.37"/>
                    <measurement group_id="B4" value="166.6" spread="11.86"/>
                    <measurement group_id="B5" value="165.1" spread="7.58"/>
                    <measurement group_id="B6" value="167.8" spread="9.05"/>
                    <measurement group_id="B7" value="164.3" spread="8.74"/>
                    <measurement group_id="B8" value="166.3" spread="9.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.4" spread="9.49"/>
                    <measurement group_id="B2" value="50.2" spread="7.36"/>
                    <measurement group_id="B3" value="57.4" spread="10.58"/>
                    <measurement group_id="B4" value="58.7" spread="9.21"/>
                    <measurement group_id="B5" value="52.4" spread="7.21"/>
                    <measurement group_id="B6" value="53.3" spread="9.41"/>
                    <measurement group_id="B7" value="56.1" spread="10.80"/>
                    <measurement group_id="B8" value="55.0" spread="9.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.9" spread="3.66"/>
                    <measurement group_id="B2" value="18.4" spread="1.98"/>
                    <measurement group_id="B3" value="21.0" spread="4.64"/>
                    <measurement group_id="B4" value="21.3" spread="3.34"/>
                    <measurement group_id="B5" value="19.2" spread="1.86"/>
                    <measurement group_id="B6" value="18.8" spread="2.15"/>
                    <measurement group_id="B7" value="20.8" spread="3.29"/>
                    <measurement group_id="B8" value="19.9" spread="3.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HIV Status</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="13"/>
                    <measurement group_id="B6" value="14"/>
                    <measurement group_id="B7" value="11"/>
                    <measurement group_id="B8" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Doubtful</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                    <measurement group_id="B8" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-14).</title>
        <time_frame>14 consecutive days of treatment</time_frame>
        <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
        <group_list>
          <group group_id="O1">
            <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O2">
            <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O3">
            <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O4">
            <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O5">
            <title>Pyrazinamide (Z)</title>
            <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O6">
            <title>Clofazimine (C)</title>
            <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O7">
            <title>Rifafour</title>
            <description>Rifafour on Days 1 to 14, dosed by weight</description>
          </group>
        </group_list>
        <measure>
          <title>Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-14).</title>
          <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
          <units>log10CFU/ml/day</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="13"/>
                <count group_id="O5" value="15"/>
                <count group_id="O6" value="14"/>
                <count group_id="O7" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.115" lower_limit="0.039" upper_limit="0.189"/>
                    <measurement group_id="O2" value="0.167" lower_limit="0.075" upper_limit="0.257"/>
                    <measurement group_id="O3" value="0.076" lower_limit="0.005" upper_limit="0.145"/>
                    <measurement group_id="O4" value="0.124" lower_limit="0.035" upper_limit="0.214"/>
                    <measurement group_id="O5" value="0.036" lower_limit="-0.026" upper_limit="0.099"/>
                    <measurement group_id="O6" value="-0.017" lower_limit="-0.085" upper_limit="0.053"/>
                    <measurement group_id="O7" value="0.151" lower_limit="0.071" upper_limit="0.232"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 0-2)</title>
        <time_frame>Days 0-2</time_frame>
        <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
        <group_list>
          <group group_id="O1">
            <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O2">
            <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O3">
            <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O4">
            <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O5">
            <title>Pyrazinamide (Z)</title>
            <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O6">
            <title>Clofazimine (C)</title>
            <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O7">
            <title>Rifafour</title>
            <description>Rifafour on Days 1 to 14, dosed by weight</description>
          </group>
        </group_list>
        <measure>
          <title>EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 0-2)</title>
          <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
          <units>log10CFU/ml/day</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="13"/>
                <count group_id="O5" value="15"/>
                <count group_id="O6" value="14"/>
                <count group_id="O7" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.161" lower_limit="0.042" upper_limit="0.279"/>
                    <measurement group_id="O2" value="0.196" lower_limit="0.061" upper_limit="0.330"/>
                    <measurement group_id="O3" value="0.062" lower_limit="-0.045" upper_limit="0.161"/>
                    <measurement group_id="O4" value="0.132" lower_limit="0.008" upper_limit="0.262"/>
                    <measurement group_id="O5" value="0.080" lower_limit="-0.028" upper_limit="0.209"/>
                    <measurement group_id="O6" value="0.018" lower_limit="-0.089" upper_limit="0.125"/>
                    <measurement group_id="O7" value="0.141" lower_limit="0.039" upper_limit="0.251"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 7-14)</title>
        <time_frame>Day 7-14</time_frame>
        <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
        <group_list>
          <group group_id="O1">
            <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O2">
            <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O3">
            <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O4">
            <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O5">
            <title>Pyrazinamide (Z)</title>
            <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O6">
            <title>Clofazimine (C)</title>
            <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O7">
            <title>Rifafour</title>
            <description>Rifafour on Days 1 to 14, dosed by weight</description>
          </group>
        </group_list>
        <measure>
          <title>EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 7-14)</title>
          <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
          <units>log10CFU/ml/day</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="13"/>
                <count group_id="O5" value="15"/>
                <count group_id="O6" value="14"/>
                <count group_id="O7" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.085" lower_limit="-0.013" upper_limit="0.175"/>
                    <measurement group_id="O2" value="0.146" lower_limit="0.033" upper_limit="0.248"/>
                    <measurement group_id="O3" value="0.085" lower_limit="-0.006" upper_limit="0.182"/>
                    <measurement group_id="O4" value="0.118" lower_limit="-0.017" upper_limit="0.250"/>
                    <measurement group_id="O5" value="0.022" lower_limit="-0.058" upper_limit="0.101"/>
                    <measurement group_id="O6" value="-0.038" lower_limit="-0.130" upper_limit="0.046"/>
                    <measurement group_id="O7" value="0.157" lower_limit="0.048" upper_limit="0.267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EBA Expressed as the Daily Percentage Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)</title>
        <time_frame>Days 0-14</time_frame>
        <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
        <group_list>
          <group group_id="O1">
            <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O2">
            <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O3">
            <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O4">
            <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O5">
            <title>Pyrazinamide (Z)</title>
            <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O6">
            <title>Clofazimine (C)</title>
            <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-1414</description>
          </group>
          <group group_id="O7">
            <title>Rifafour</title>
            <description>Rifafour on Days 1 to 14, dosed by weight</description>
          </group>
        </group_list>
        <measure>
          <title>EBA Expressed as the Daily Percentage Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)</title>
          <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
          <units>percentage of change in time/day</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="13"/>
                <count group_id="O5" value="15"/>
                <count group_id="O6" value="14"/>
                <count group_id="O7" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" lower_limit="4.2" upper_limit="8.6"/>
                    <measurement group_id="O2" value="7.0" lower_limit="5.1" upper_limit="9.4"/>
                    <measurement group_id="O3" value="4.3" lower_limit="2.9" upper_limit="5.7"/>
                    <measurement group_id="O4" value="4.9" lower_limit="3.3" upper_limit="6.8"/>
                    <measurement group_id="O5" value="2.0" lower_limit="0.8" upper_limit="3.4"/>
                    <measurement group_id="O6" value="-0.3" lower_limit="-1.5" upper_limit="1.0"/>
                    <measurement group_id="O7" value="6.3" lower_limit="4.8" upper_limit="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Day 0-2)</title>
        <time_frame>Day 0-2</time_frame>
        <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
        <group_list>
          <group group_id="O1">
            <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O2">
            <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O3">
            <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O4">
            <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O5">
            <title>Pyrazinamide (Z)</title>
            <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O6">
            <title>Clofazimine (C)</title>
            <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O7">
            <title>Rifafour</title>
            <description>Rifafour on Days 1 to 14, dosed by weight</description>
          </group>
        </group_list>
        <measure>
          <title>EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Day 0-2)</title>
          <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
          <units>percentage of change in time/day</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="13"/>
                <count group_id="O5" value="15"/>
                <count group_id="O6" value="14"/>
                <count group_id="O7" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6" lower_limit="8.0" upper_limit="13.3"/>
                    <measurement group_id="O2" value="13.2" lower_limit="9.0" upper_limit="17.9"/>
                    <measurement group_id="O3" value="6.0" lower_limit="4.2" upper_limit="7.8"/>
                    <measurement group_id="O4" value="9.1" lower_limit="6.5" upper_limit="12.2"/>
                    <measurement group_id="O5" value="4.7" lower_limit="2.4" upper_limit="7.5"/>
                    <measurement group_id="O6" value="2.1" lower_limit="-0.5" upper_limit="5.0"/>
                    <measurement group_id="O7" value="12.9" lower_limit="8.9" upper_limit="17.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Days 7-14)</title>
        <time_frame>Days 7-14</time_frame>
        <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
        <group_list>
          <group group_id="O1">
            <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O2">
            <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O3">
            <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O4">
            <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
            <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O5">
            <title>Pyrazinamide (Z)</title>
            <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
          </group>
          <group group_id="O6">
            <title>Clofazimine (C)</title>
            <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
          </group>
          <group group_id="O7">
            <title>Rifafour</title>
            <description>Rifafour on Days 1 to 14, dosed by weight</description>
          </group>
        </group_list>
        <measure>
          <title>EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Days 7-14)</title>
          <population>Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data</population>
          <units>percentage of change in time/day</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="13"/>
                <count group_id="O5" value="15"/>
                <count group_id="O6" value="14"/>
                <count group_id="O7" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" lower_limit="1.5" upper_limit="6.2"/>
                    <measurement group_id="O2" value="4.5" lower_limit="2.9" upper_limit="6.2"/>
                    <measurement group_id="O3" value="3.1" lower_limit="1.7" upper_limit="4.7"/>
                    <measurement group_id="O4" value="3.0" lower_limit="1.5" upper_limit="4.9"/>
                    <measurement group_id="O5" value="0.8" lower_limit="-0.7" upper_limit="2.3"/>
                    <measurement group_id="O6" value="-1.3" lower_limit="-2.9" upper_limit="0.4"/>
                    <measurement group_id="O7" value="4.4" lower_limit="2.9" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="E2">
          <title>TMC207, PA-824 and Pyrazinamide (J-PA-Z)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
        </group>
        <group group_id="E3">
          <title>TMC207, PA-824 and Clofazimine (J-PA-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
PA-824 (PA): 200 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="E4">
          <title>TMC207, Pyrazinamide and Clofazimine (J-Z-C)</title>
          <description>TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14&#xD;
pyrazinamide (Z): 1500 mg on Days 1 to 14&#xD;
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="E5">
          <title>Pyrazinamide (Z)</title>
          <description>pyrazinamide (Z): 1500 mg on Days 1 to 14</description>
        </group>
        <group group_id="E6">
          <title>Clofazimine (C)</title>
          <description>clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14</description>
        </group>
        <group group_id="E7">
          <title>Rifafour</title>
          <description>Rifafour on Days 1 to 14, dosed by weight</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="8" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrioventricular Block First Degree</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Bundle Branch Block Right</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Cerumen Impaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Lacrimation Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal Tenderness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Epigastric Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Salivary Gland Enlargement</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vessel Puncture Site Pain</sub_title>
                <description>and Administration site conditions</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oedema, peripheral</sub_title>
                <description>and Administration site conditions</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Tooth Abcess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oral Candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Tinea Versicolour</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vulvovaginal Candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Foreign Body</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Ligament Sprain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Procedural Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>QT prolonged</sub_title>
                <description>Electrocardiogram</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>ALT Increased</sub_title>
                <description>Laboratory toxicities</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>AST Increased</sub_title>
                <description>Laboratory toxicities</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <description>Laboratory toxicities</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <description>Laboratory toxicities</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <description>Laboratory toxicities</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood Creatine Phosphokinase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood Urea Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hepatic Enzyme Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pleuritic Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash Papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin Discolouration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash Pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin Hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Blood Pressure inadequately controlled</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator or any Sub-Investigator shall submit any oral or written publication or abstract concerning this study to the Sponsor not less than thirty (30) days prior to submission to any journal, other publication or meeting, for review and removal of confidential information.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Daniel E. Everitt, MD, Vice President and Senior Medical Officer</name_or_title>
      <organization>Global Alliance for TB Drug Development</organization>
      <phone>212-227-7540</phone>
      <email>Dan.Everitt@tballiance.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01691534
org study id: NC-003-(C-J-Pa-Z)
nct id: NCT01691534
lead sponsor: 
has dmc: No
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral
      administration of TMC207 plus PA-824 plus Pyrazinamide plus Clofazimine, TMC207 plus PA-824
      plus Pyrazinamide, TMC207 plus PA-824 plus Clofazimine alone, TMC207 plus Pyrazinamide plus
      Clofazimine, Pyrazinamide alone, Clofazimine alone, and standard first line TB treatment as
      per South African TB Guidelines (Rifafour e-275) as determined by the rate of change of log
      CFU per ml sputum over the time period Day 0-14 in participants with smear positive pulmonary
      tuberculosis (TB). A control group will receive standard treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-14).
time frame: 14 consecutive days of treatment
measure: EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 0-2)
time frame: Days 0-2
measure: EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 7-14)
time frame: Day 7-14
measure: EBA Expressed as the Daily Percentage Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)
time frame: Days 0-14
measure: EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Day 0-2)
time frame: Day 0-2
measure: EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Days 7-14)
time frame: Days 7-14
arm group label: TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)
arm group type: Experimental
description: TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus PA-824 200mg Days 1-14 plus pyrazinamide 1500mg Days 1-14 plus clofazimine 300mg Days 1-3 and Clofazamine 100mg Days 4-14
arm group label: TMC207, PA-824 and pyrazinamide (J-PA-Z)
arm group type: Experimental
description: TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus PA-824 200mg Days 1-14 plus pyrazinamide 1500mg Days 1-14
arm group label: TMC207, PA-824 and clofazimine (J-PA-C)
arm group type: Experimental
description: TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus PA-824 200mg Days 1-14 plus clofazimine 300mg Days 1-3 and clofazimine 100mg Days 4-14
arm group label: TMC207, pyrazinamide and clofazimine (J-Z-C)
arm group type: Experimental
description: TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14 plus pyrazinamide 1500mg Days 1-14 plus clofazimine 300mg Days 1-3 and Clofazimine 100mg Days 4-14
arm group label: pyrazinamide (Z)
arm group type: Experimental
description: pyrazinamide 1500mg Days 1-14
arm group label: clofazimine (C)
arm group type: Experimental
description: Clofazimine 300mg Days 1-3 and Clofazimine 100mg Days 4-14
arm group label: Rifafour
arm group type: Active Comparator
description: Rifafour e-275 mg dosed by weight
intervention type: Drug
intervention name: TMC207 (J)
description: TMC207 400 mg Day 1; 300mg Day 2; 200mg Days 3-14
arm group label: TMC207, PA-824 and clofazimine (J-PA-C)
arm group label: TMC207, PA-824 and pyrazinamide (J-PA-Z)
arm group label: TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)
arm group label: TMC207, pyrazinamide and clofazimine (J-Z-C)
intervention type: Drug
intervention name: PA-824 (PA)
description: PA-824 200mg Days 1-14
arm group label: TMC207, PA-824 and clofazimine (J-PA-C)
arm group label: TMC207, PA-824 and pyrazinamide (J-PA-Z)
arm group label: TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)
intervention type: Drug
intervention name: pyrazinamide (Z)
description: 1500mg Days 1-14 Dosed by Weight
arm group label: TMC207, PA-824 and pyrazinamide (J-PA-Z)
arm group label: TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)
arm group label: TMC207, pyrazinamide and clofazimine (J-Z-C)
arm group label: pyrazinamide (Z)
intervention type: Drug
intervention name: clofazimine (C)
description: clofazimine 300mg Days 1-3 and clofazimine 100mg Days 4-14
arm group label: TMC207, PA-824 and clofazimine (J-PA-C)
arm group label: TMC207, PA-824, pyrazinamide and clofazimine (J-PA-Z-C)
arm group label: TMC207, pyrazinamide and clofazimine (J-Z-C)
arm group label: clofazimine (C)
intervention type: Drug
intervention name: Rifafour
description: Rifafour e-275 mg dosed by weight
arm group label: Rifafour
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Andreas Diacon, MD
role: Principal Investigator
affiliation: Karl Bremer Hospital, Cape Town South Africa
facility: 
facility: 
country: South Africa
url: http://www.tballiance.org/home/home.php
description: Sponsor home page
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Tuberculosis, Pulmonary
mesh term: Pyrazinamide
mesh term: Clofazimine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 