<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/NCT01674218</url>
  </required_header>
  <id_info>
    <org_study_id>10-0058</org_study_id>
    <secondary_id>N01AI80024C</secondary_id>
    <nct_id>NCT01674218</nct_id>
  </id_info>
  <brief_title>Effect of PA-824 and of PA-824 Plus Moxifloxacin on the QTc Interval in Healthy Volunteers</brief_title>
  <official_title>Phase I, Double-Blind, Randomized, Single-Center, Five-Period Crossover Study to Assess the Effects of Single Oral Doses of 400 mg and 1000 mg of PA-824 and 400 mg of PA-824 Plus 400 mg of Moxifloxacin on QTc Interval Compared to Placebo, Using AVELOX™ (Moxifloxacin) as a Positive Control, in Healthy Male and Female Volunteers Aged 18 to 45 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <brief_summary>
    <textblock>
      This is a Phase I, single-center, double-blinded, randomized, placebo-controlled, five-period&#xD;
      cross-over clinical study of PA-824 to evaluate the effect of PA-824 and of PA-824 plus&#xD;
      moxifloxacin on cardiac repolarization (QT/QTc interval duration) in a total of 75 healthy&#xD;
      male and female participants, aged 18 to 45 years. Moxifloxacin will be used as an active&#xD;
      control. Participants will be blinded to the treatments they will receive. The study consists&#xD;
      of a screening period up to 26 days; enrollment, 1 day; five in-patient treatment periods&#xD;
      consisting of an admission day (except in the first treatment period, when the pre-dose day&#xD;
      is the baseline), dosing day and two post-dosing days; an out-patient period of at least&#xD;
      three days and not more than 10 days between treatment periods; and a final visit 7 - 14 days&#xD;
      after discharge from the last treatment period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, single-center, double-blinded, randomized, placebo-controlled, five-period&#xD;
      cross-over clinical study of PA-824 to evaluate the effect of PA-824 and of PA-824 plus&#xD;
      moxifloxacin on cardiac repolarization (QT/QTc interval duration) in healthy male and female&#xD;
      participants. Moxifloxacin will be used as an active control. Participants will be blinded to&#xD;
      the treatments they will receive. The study consists of a screening period up to 26 days;&#xD;
      enrollment, 1 day; five in-patient treatment periods consisting of an admission day (except&#xD;
      in the first treatment period, when the pre-dose day is the baseline), dosing day and two&#xD;
      post-dosing days; an out-patient period of at least three days and not more than 10 days&#xD;
      between treatment periods; and a final visit 7 - 14 days after discharge from the last&#xD;
      treatment period. During the study, the subjects will receive each one of the following five&#xD;
      treatments: Treatment A: PA-824 placebo and moxifloxacin placebo; Treatment B: PA-824 400 mg&#xD;
      plus moxifloxacin placebo; Treatment C: PA-824 1000 mg plus moxifloxacin placebo; Treatment&#xD;
      D: PA-824 placebo plus moxifloxacin 400 mg; Treatment E: PA-824 400 mg plus moxifloxacin 400&#xD;
      mg. The primary objective is to evaluate the effect of single-dose administration of PA-824&#xD;
      400 mg and 1000 mg versus placebo on the QTcI interval. A total of 75 randomized (in order to&#xD;
      have at least 60 evaluable) healthy male and female volunteers, aged 18 to 45 years will be&#xD;
      enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">December 2012</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of PA-824 on cardiac ventricular repolarization (CVR) as measured by QT interval corrected for heart rate using individual-specific formula (QTcI) during the first 24 hours following dosing of PA-824 in healthy volunteers as compared to placebo.</measure>
    <time_frame>24 hours after dosing of PA-824</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of PA-824 on CVR measured by QT interval corrected for heart rate by group-specific formula (QTcN), Fridericia (QTcF) and Bazett (QTcB) formulae during the first 24 hours following dosing in healthy volunteers compared to placebo.</measure>
    <time_frame>24 hours after dosing of PA-824</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of PA-824 plus moxifloxacin on CVR as measured by QT and QT corrected for heart rate (QTcI, QTcN, QTcF, and QTcB) during the first 24 hours following dosing of PA-824 in healthy volunteers as compared to placebo.</measure>
    <time_frame>24 hours after dosing of PA-824</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of Moxifloxacin on CVR as measured by QTcI, QTcN, QTcF, and QTcB, HR and non-QTc ECG intervals (HR, and PR, QRS, and RR intervals) during the first 24 hours following dosing of PA-824 in healthy volunteers as compared to placebo.</measure>
    <time_frame>24 hours after dosing of PA-824</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability evaluated by ophthalmology exam.</measure>
    <time_frame>Screening , Day -2 and Day 45</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of the QTcI, QTcN, QTcF, QTcB, PR, QRS, and RR intervals and heart rate matched to PK sampling times to allow determination of any PK / pharmacodynamic effect of PA-824 alone and in combination with moxifloxacin.</measure>
    <time_frame>Day 1 of each treatment period at 0 h (pre-dose) and 0.25, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72(±4) and 96(±4) hrs (post-dose).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability evaluated by standard 12-lead ECGs obtained pre-dose and 2, 4, 7 and 10 hrs post-dose on treatment days.</measure>
    <time_frame>ECGs: pre-dose, 2, 4, 7 &amp; 10 hrs post dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability evaluated by continuous AE monitoring throughout the study; physical exams, and laboratory evaluations</measure>
    <time_frame>Day 0 to Day 45</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum pharmacokinetics (PK) of 400 mg and 1000 mg of PA-824 and of 400 mg of PA-824 plus 400 mg of moxifloxacin for up to 5 days following dosing.</measure>
    <time_frame>Day 1 of each treatment period at 0 h (pre-dose) and 0.25, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72(±4) and 96(±4) hrs (post-dose).</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Treatment E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PA-824 400 mg plus moxifloxacin 400 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PA-824 placebo plus moxifloxacin 400 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PA-824 1000 mg plus moxifloxacin placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PA-824 400 mg plus moxifloxacin placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>PA-824 placebo and moxifloxacin placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <description>Moxifloxacin will be given orally to the following treatment groups, in combination with either PA-824 or PA-824 placebo: Treatment D: 400 mg + PA-824 placebo; Treatment E: 400 mg + PA-824 400 mg. Subjects will cross-over to the next Treatment Group after a 6-day washout period.</description>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_label>Treatment E</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PA-824</intervention_name>
    <description>PA-824 will be given orally to the following treatment groups, together with either moxifloxacin or moxifloxacin placebo: Treatment B: 400 mg + moxifloxacin placebo; Treatment C: 1000 mg + moxifloxacin placebo; Treatment E: 400 mg + moxifloxacin 400 mg. Subjects will cross-over to the next Treatment Group after a 6-day washout period.</description>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment E</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets to match Moxifloxacin or PA-824 will be given orally, in combination with either moxifloxacin or PA-824: Treatment A: PA-824 placebo + moxifloxacin placebo; Treatment B: PA-824 400 mg + moxifloxacin placebo; Treatment C: PA-824 1000 mg + moxifloxacin placebo Treatment D: PA-824 placebo + moxafloxacin 400 mg. Subjects will cross-over to the next Treatment Group after a 6-day washout period.</description>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject must be 18 to 45 years of age (inclusive).&#xD;
&#xD;
          -  Subject must be a healthy male or female volunteer as determined by medical history,&#xD;
             physical examination, 12-lead ECG and laboratory evaluations (hematology, clinical&#xD;
             chemistries and urinalysis tests) within study-defined ranges at Screening. (See&#xD;
             Appendix B for acceptable ranges of laboratory and vital signs assessments).&#xD;
&#xD;
          -  Body Mass Index (BMI) must be between 18 and 30 kg/m^2 inclusive.&#xD;
&#xD;
          -  Subject must be non-tobacco/nicotine using (3-month minimum).&#xD;
&#xD;
          -  Subject must be Tuberculin Skin Test/Purified Protein Derivative (TST/PPD) negative&#xD;
             (within the previous 1 year) at Screening. The TST/PPD may be omitted if the subject&#xD;
             presents written evidence of having a negative test during the previous 12 months.&#xD;
&#xD;
          -  Subject must be able to give voluntary written informed consent before any study&#xD;
             related procedure is performed.&#xD;
&#xD;
          -  If female, has no childbearing potential (as defined below) or agrees to avoid&#xD;
             becoming pregnant from the day of screening through one week after the last dose by&#xD;
             using one of the following acceptable methods of birth control in addition to the use&#xD;
             of a barrier method (condom) by the male partner (even if vasectomized):&#xD;
&#xD;
               1. Hormonal contraceptives; or&#xD;
&#xD;
               2. intrauterine contraceptive device; or&#xD;
&#xD;
               3. diaphragm in combination with contraceptive jelly, cream, or foam; or&#xD;
&#xD;
               4. spermicide; or&#xD;
&#xD;
               5. abstinence. Non-childbearing potential is defined as being post-menopausal for at&#xD;
                  least 2 years, status after bilateral tubal ligation for at least 1 year, status&#xD;
                  after bilateral oophorectomy or status after hysterectomy.&#xD;
&#xD;
        If male, agrees to avoid fathering a child from the day of screening to three months after&#xD;
        the last dose.&#xD;
&#xD;
          -  All female subjects must have a negative serum pregnancy test at Screening, Enrollment&#xD;
             (Day-2) and at check-in for each treatment period.&#xD;
&#xD;
          -  Subject agrees not to donate blood during the study and up to 14 days after the end of&#xD;
             the last treatment period.&#xD;
&#xD;
          -  Subject agrees to comply with all study requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of clinically significant acute illness (resolved within 4 weeks of&#xD;
             screening) or history of cardiac arrhythmias or unexplained syncope or presence of&#xD;
             cardiac, vascular gastrointestinal, renal, hepatic, neurologic, hematologic,&#xD;
             endocrine, oncologic, pulmonary, immunologic, or psychiatric disease or any other&#xD;
             condition which, in the opinion of the Site Principal Investigator (PI), would&#xD;
             jeopardize the safety of the subject or impact the validity of the study results.&#xD;
&#xD;
          -  Subject has had major surgery within 4 weeks of screening.&#xD;
&#xD;
          -  has an uncontrolled intercurrent illness (i.e., active infection) or fever (oral&#xD;
             temperature &gt;/=100 degrees Fahrenheit or &gt;/= 37.7 degrees Celsius) at screening.&#xD;
&#xD;
          -  History of lens opacity or evidence of lens opacity on screening ophthalmologic&#xD;
             examination or any other clinically significant ophthalmic dysfunction or disease.&#xD;
&#xD;
          -  Subject has been on an abnormal diet during the 4 weeks preceding screening. Abnormal&#xD;
             diet is defined as a diet in which the subject has a significant change in eating&#xD;
             habits (e.g., liquid diet only) and an unbalanced diet (e.g., protein only, high fat,&#xD;
             low carbohydrate, etc.).&#xD;
&#xD;
          -  Subject has engaged in strenuous physical activity or consumed alcohol, grapefruit,&#xD;
             and caffeine- or methylxanthine-containing beverages from 48 hours before reporting to&#xD;
             the clinic for enrollment until discharge from the clinical site in the last treatment&#xD;
             period.&#xD;
&#xD;
          -  Previous participation in any other study of PA-824.&#xD;
&#xD;
          -  History of seizures (other than febrile seizures during childhood) or known or&#xD;
             suspected Central Nervous System (CNS) disorders that may predispose to seizures.&#xD;
&#xD;
          -  History of photosensitivity or phototoxicity reactions after use of quinolones or&#xD;
             other drugs.&#xD;
&#xD;
          -  History of allergy or severe side-effects with nitroimidazoles (e.g., Flagyl and&#xD;
             related substances and azole antifungals or aromatase inhibitors).&#xD;
&#xD;
          -  History of allergy to moxifloxacin or any fluoroquinolone antibiotic.&#xD;
&#xD;
          -  History of tendinopathy associated with quinolones or other drugs, including&#xD;
             glucocorticoids, or a condition that predisposes to tendon rupture.&#xD;
&#xD;
          -  Subject has received an investigational drug in a clinical trial within 30 days prior&#xD;
             to screening.&#xD;
&#xD;
          -  Subject has used any over the counter (OTC) medication, including vitamins and herbal&#xD;
             supplements, antacids, cough and cold medications, within 7 days prior to Day 1 of&#xD;
             treatment with study drugs or during the study, unless in the opinion of the PI, the&#xD;
             substance would not likely impact on the conduct of this study.&#xD;
&#xD;
          -  Subject has used any prescription medication, except hormonal contraceptives, within&#xD;
             30 days prior to Day 1 of treatment with study drugs or during the study, unless in&#xD;
             the opinion of the PI, the substance would not likely impact the conduct of this&#xD;
             study.&#xD;
&#xD;
          -  Subject has any current medical condition requiring treatment with medication, either&#xD;
             prescription or OTC.&#xD;
&#xD;
          -  Subject has been treated with any known CYP450 enzyme altering drugs, such as azoles,&#xD;
             antifungals, barbiturates, phenothiazines, cimetidine, carbamazepine, etc., except&#xD;
             hormonal contraceptives, within 30 days prior to Day 1 of treatment with study drugs.&#xD;
&#xD;
          -  Subject has been treated with any drugs known to prolong the electrocardiographic QT&#xD;
             interval within 30 days prior to Day 1 of treatment with study drugs or has history of&#xD;
             excessive chronic caffeine (&gt; 6-8 oz cups of brewed coffee daily), or theophylline (&gt;&#xD;
             600 mg/day), or ephedrine (&gt;300 mg/day) use..&#xD;
&#xD;
          -  Subject has a positive blood screen for HIV, hepatitis B surface antigen (HBsAg), or&#xD;
             hepatitis C antibody.&#xD;
&#xD;
          -  Subject has a positive history for alcohol abuse or dependence and/or a positive urine&#xD;
             screen test for alcohol and drugs of abuse [amphetamines, barbiturates,&#xD;
             benzodiazepines, cocaine metabolites, marijuana, opiates, phencyclidine (PCP)] at&#xD;
             screening or at any check-in prior to receiving study drugs.&#xD;
&#xD;
          -  Subject has a baseline QTcF interval &gt;440 msec (males) or &gt;450 msec (females) or a&#xD;
             history of prolonged QTc interval or a family history of Long QT Syndrome or premature&#xD;
             cardiac death or sudden death without a preceding diagnosis of a condition that could&#xD;
             be causative of sudden death (such as known coronary artery disease or CHF or terminal&#xD;
             cancer).&#xD;
&#xD;
          -  Subject has any clinically significant ECG abnormality in the opinion of the site&#xD;
             principal investigator (PI) at Screening, Enrollment (Day-2), Baseline (Day-1), and at&#xD;
             any check-in day prior to receiving study drugs.&#xD;
&#xD;
          -  Subject with ECGs deemed by the PI to have T -wave morphology unfavorable for&#xD;
             consistently accurate QT measurement and presence of artifacts that cannot be readily&#xD;
             eliminated.&#xD;
&#xD;
          -  Subject has hypokalemia, hypomagnesemia, or hypocalcemia, or a history of eating&#xD;
             disorder.&#xD;
&#xD;
          -  Subject has serum creatinine, blood urea nitrogen (BUN) or transaminase measurements&#xD;
             above the upper limit of the normal range at screening.&#xD;
&#xD;
          -  Subject has lived with a person having active Tuberculosis (TB) or has traveled to an&#xD;
             area of endemic TB within the past 12 months prior to Screening.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Subject has donated blood within the past 30 days prior to Day 1 of treatment with&#xD;
             study drugs.&#xD;
&#xD;
          -  Subject is an employee of or family member of an employee of Quintiles, or DynPort&#xD;
             Vaccine Company LLC (DVC) or personnel participating in the conduct of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Quintiles Phase I Services - Overland Park</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211-1553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2013</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>November 13, 2014</last_update_submitted>
  <last_update_submitted_qc>November 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 14, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tuberculosis, safety, PA-824, QTc interval, moxifloxacin, healthy volunteers, crossover</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01674218
org study id: 10-0058
secondary id: N01AI80024C
nct id: NCT01674218
lead sponsor: 
This is a Phase I, single-center, double-blinded, randomized, placebo-controlled, five-period
      cross-over clinical study of PA-824 to evaluate the effect of PA-824 and of PA-824 plus
      moxifloxacin on cardiac repolarization (QT/QTc interval duration) in a total of 75 healthy
      male and female participants, aged 18 to 45 years. Moxifloxacin will be used as an active
      control. Participants will be blinded to the treatments they will receive. The study consists
      of a screening period up to 26 days; enrollment, 1 day; five in-patient treatment periods
      consisting of an admission day (except in the first treatment period, when the pre-dose day
      is the baseline), dosing day and two post-dosing days; an out-patient period of at least
      three days and not more than 10 days between treatment periods; and a final visit 7 - 14 days
      after discharge from the last treatment period.
This is a Phase I, single-center, double-blinded, randomized, placebo-controlled, five-period
      cross-over clinical study of PA-824 to evaluate the effect of PA-824 and of PA-824 plus
      moxifloxacin on cardiac repolarization (QT/QTc interval duration) in healthy male and female
      participants. Moxifloxacin will be used as an active control. Participants will be blinded to
      the treatments they will receive. The study consists of a screening period up to 26 days;
      enrollment, 1 day; five in-patient treatment periods consisting of an admission day (except
      in the first treatment period, when the pre-dose day is the baseline), dosing day and two
      post-dosing days; an out-patient period of at least three days and not more than 10 days
      between treatment periods; and a final visit 7 - 14 days after discharge from the last
      treatment period. During the study, the subjects will receive each one of the following five
      treatments: Treatment A: PA-824 placebo and moxifloxacin placebo; Treatment B: PA-824 400 mg
      plus moxifloxacin placebo; Treatment C: PA-824 1000 mg plus moxifloxacin placebo; Treatment
      D: PA-824 placebo plus moxifloxacin 400 mg; Treatment E: PA-824 400 mg plus moxifloxacin 400
      mg. The primary objective is to evaluate the effect of single-dose administration of PA-824
      400 mg and 1000 mg versus placebo on the QTcI interval. A total of 75 randomized (in order to
      have at least 60 evaluable) healthy male and female volunteers, aged 18 to 45 years will be
      enrolled.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Effect of PA-824 on cardiac ventricular repolarization (CVR) as measured by QT interval corrected for heart rate using individual-specific formula (QTcI) during the first 24 hours following dosing of PA-824 in healthy volunteers as compared to placebo.
time frame: 24 hours after dosing of PA-824
measure: Effect of PA-824 on CVR measured by QT interval corrected for heart rate by group-specific formula (QTcN), Fridericia (QTcF) and Bazett (QTcB) formulae during the first 24 hours following dosing in healthy volunteers compared to placebo.
time frame: 24 hours after dosing of PA-824
measure: Effect of PA-824 plus moxifloxacin on CVR as measured by QT and QT corrected for heart rate (QTcI, QTcN, QTcF, and QTcB) during the first 24 hours following dosing of PA-824 in healthy volunteers as compared to placebo.
time frame: 24 hours after dosing of PA-824
measure: The effect of Moxifloxacin on CVR as measured by QTcI, QTcN, QTcF, and QTcB, HR and non-QTc ECG intervals (HR, and PR, QRS, and RR intervals) during the first 24 hours following dosing of PA-824 in healthy volunteers as compared to placebo.
time frame: 24 hours after dosing of PA-824
measure: Safety and tolerability evaluated by ophthalmology exam.
time frame: Screening , Day -2 and Day 45
measure: Analysis of the QTcI, QTcN, QTcF, QTcB, PR, QRS, and RR intervals and heart rate matched to PK sampling times to allow determination of any PK / pharmacodynamic effect of PA-824 alone and in combination with moxifloxacin.
time frame: Day 1 of each treatment period at 0 h (pre-dose) and 0.25, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72(±4) and 96(±4) hrs (post-dose).
measure: Safety and tolerability evaluated by standard 12-lead ECGs obtained pre-dose and 2, 4, 7 and 10 hrs post-dose on treatment days.
time frame: ECGs: pre-dose, 2, 4, 7 & 10 hrs post dose.
measure: Safety and tolerability evaluated by continuous AE monitoring throughout the study; physical exams, and laboratory evaluations
time frame: Day 0 to Day 45
measure: Serum pharmacokinetics (PK) of 400 mg and 1000 mg of PA-824 and of 400 mg of PA-824 plus 400 mg of moxifloxacin for up to 5 days following dosing.
time frame: Day 1 of each treatment period at 0 h (pre-dose) and 0.25, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72(±4) and 96(±4) hrs (post-dose).
arm group label: Treatment E
arm group type: Experimental
description: PA-824 400 mg plus moxifloxacin 400 mg
arm group label: Treatment D
arm group type: Active Comparator
description: PA-824 placebo plus moxifloxacin 400 mg
arm group label: Treatment C
arm group type: Experimental
description: PA-824 1000 mg plus moxifloxacin placebo
arm group label: Treatment B
arm group type: Experimental
description: PA-824 400 mg plus moxifloxacin placebo
arm group label: Treatment A
arm group type: Placebo Comparator
description: PA-824 placebo and moxifloxacin placebo
intervention type: Drug
intervention name: Moxifloxacin
description: Moxifloxacin will be given orally to the following treatment groups, in combination with either PA-824 or PA-824 placebo: Treatment D: 400 mg + PA-824 placebo; Treatment E: 400 mg + PA-824 400 mg. Subjects will cross-over to the next Treatment Group after a 6-day washout period.
arm group label: Treatment D
arm group label: Treatment E
intervention type: Drug
intervention name: PA-824
description: PA-824 will be given orally to the following treatment groups, together with either moxifloxacin or moxifloxacin placebo: Treatment B: 400 mg + moxifloxacin placebo; Treatment C: 1000 mg + moxifloxacin placebo; Treatment E: 400 mg + moxifloxacin 400 mg. Subjects will cross-over to the next Treatment Group after a 6-day washout period.
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment E
intervention type: Other
intervention name: Placebo
description: Placebo tablets to match Moxifloxacin or PA-824 will be given orally, in combination with either moxifloxacin or PA-824: Treatment A: PA-824 placebo + moxifloxacin placebo; Treatment B: PA-824 400 mg + moxifloxacin placebo; Treatment C: PA-824 1000 mg + moxifloxacin placebo Treatment D: PA-824 placebo + moxafloxacin 400 mg. Subjects will cross-over to the next Treatment Group after a 6-day washout period.
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Moxifloxacin