<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/NCT02257398</url>
  </required_header>
  <id_info>
    <org_study_id>115775</org_study_id>
    <nct_id>NCT02257398</nct_id>
  </id_info>
  <brief_title>Placebo and Moxifloxacin Controlled Cardiac Conduction Study of GSK2140944 in Healthy Volunteers</brief_title>
  <official_title>A Phase I, Randomized, Double-Blinded, Placebo- and Moxifloxacin-Controlled, 4-Period Crossover Study to Evaluate the Effect of GSK2140944 on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is Phase I, 4-period, randomized, active-and placebo-controlled, double-blind crossover,&#xD;
      single-dose study to evaluate the effects of a therapeutic (1000 milligram [mg]) and&#xD;
      supratherapeutic (1800 mg) dose of GSK2140944 with a positive control (moxifloxacin 400 mg)&#xD;
      and placebo on the corrected QT interval (QTc) as assessed by continuous 12-lead Holter&#xD;
      electrocardiograms (ECGs) in approximately 55 healthy volunteers.&#xD;
&#xD;
      All subjects will receive single doses of GSK2140944 1000 mg, GSK2140944 1800 mg,&#xD;
      moxifloxacin 400 mg, and placebo in a randomized sequence. A double-dummy approach will be&#xD;
      used to maintain blinding. Thus, on each dosing day, moxifloxacin or moxifloxacin placebo and&#xD;
      GSK2140944 or placebo will be administered.&#xD;
&#xD;
      Subjects will be screened within 30 days prior to entry to the clinic. Subjects will report&#xD;
      to the clinical unit on Day -2 of Period 1 and on Day -1 in subsequent periods. Subjects will&#xD;
      remain confined until check out procedures have been completed on Day 3 (5 days confinement&#xD;
      in Period 1 and 4 days in the following 3 periods). There will be a washout of at least 7&#xD;
      days between doses. The follow-up visit will occur 7-10 days after the final dose. Total&#xD;
      duration of the study (from screening to the follow-up visit) will be approximately 60 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2014</start_date>
  <completion_date type="Actual">March 2, 2015</completion_date>
  <primary_completion_date type="Actual">March 2, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in corrected QT interval, using the Fridericia formula (QTcF) for GSK2140944 (1000 mg and 1800 mg)</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>ECGs will be measured using a 24-hour continuous 12-lead Holter monitor. ECGs will be extracted up to 10 replicates at the following time points: at 3 time points pre-dose (45, 30, and 15 minutes prior to starting the infusion) and 0.25, 0.5, 1.0, 1.5, 2.0 (end of infusion), 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24 and 48 hours after dosing, for a total of 16 time points per treatment period</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG parameters for GSK2140944 (1000 mg and 1800 mg)</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>ECGs will be measured using a 24-hour continuous 12-lead Holter monitor at predefined timepoints. ECG parameters includes QT (QT interval), QT corrected according to the Bazett formula (QTcB), QT/RR pairs from the defined time points at which subjects are supinely resting (QTci), Individually corrected QT interval (QTcI), heart rate (HR), PR interval, and the complex of 3 of the graphical deflections seen on a typical ECG (QRS) interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Categorical outliers in ECG parameters for GSK2140944 (1000 mg and 1800 mg)</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>ECGs will be measured using a 24-hour continuous 12-lead Holter monitor at predefined time points. Categorical outliers ECG parameters includes QTc, HR, PR, and QRS interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG parameters for moxifloxacin</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>ECGs will be measured using a 24-hour continuous 12-lead Holter monitor at predefined time points. ECG parameters includes QTcF, QTcB, QTci, QTcI, QT, HR, PR, and QRS interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of pharmacokinetic (PK) parameters for GSK2140944 (1000 mg and 1800 mg)</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>PK parameters including area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]), area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration (AUC[0-t]), systemic clearance of parent drug (CL), maximum observed concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters for moxifloxacin</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>PK parameters including AUC(0-infinity), AUC(0-t), CL, apparent clearance of parent drug after oral dosing (CL/F), Cmax, λz, t1/2, tmax, Vss, Vz, apparent volume of distribution after oral dosing (Vz/F).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations and change in QTcF for GSK2140944 and moxifloxacin</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>The relationship between GSK2140944 plasma concentration following single IV administration and the baseline adjusted QTcF interval corrected for placebo will be explored</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount excreted (Ae) in urine of unchanged GSK2140944 (1000 mg and 1800 mg)</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>Urinary recovery of unchanged drug that is total amount of drug excreted in urine (Ae), calculated by adding all the fractions of drug collected over all the allotted time intervals</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of the dose (fe) excreted in urine</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>Fraction of the dose (fe) will be calculated as, percentage fe= (Ae/Dose) × 100</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance</measure>
    <time_frame>Up to 48 hours</time_frame>
    <description>Renal clearance of drug will be calculated as: Ae/ AUC(0-t)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of ECG</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>Single 12-lead safety ECGs will be obtained at predefined time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in vital sign measurements</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>Vital signs includes temperature, systolic and diastolic blood pressure and pulse rate and respiratory rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events (AEs)</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity grading of clinical laboratory test results</measure>
    <time_frame>Up to Day 48</time_frame>
    <description>Clinical laboratory parameters includes hematology, clinical chemistry, and urinalysis</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Infections, Respiratory Tract</condition>
  <arm_group>
    <arm_group_label>Sequence ABDC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be administered treatments in Sequence ABDC where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence BCAD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be administered treatments in Sequence BCAD where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence CDBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be administered treatments in Sequence CDBA where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence DACB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be administered treatments in Sequence DACB where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2140944</intervention_name>
    <description>GSK2140944 is available in dose strength 1000 mg and 1800 mg for single IV dose over 2 hours administration as a pale yellow to greyish yellow cake for reconstitution</description>
    <arm_group_label>Sequence ABDC</arm_group_label>
    <arm_group_label>Sequence BCAD</arm_group_label>
    <arm_group_label>Sequence CDBA</arm_group_label>
    <arm_group_label>Sequence DACB</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2140944 placebo</intervention_name>
    <description>GSK2140944 placebo is 0.9% sodium chloride available for single IV dose over 2 hours administration.</description>
    <arm_group_label>Sequence ABDC</arm_group_label>
    <arm_group_label>Sequence BCAD</arm_group_label>
    <arm_group_label>Sequence CDBA</arm_group_label>
    <arm_group_label>Sequence DACB</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <description>Moxifloxacin is available as pinkish red tablet with dose strength 400 mg for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water.</description>
    <arm_group_label>Sequence ABDC</arm_group_label>
    <arm_group_label>Sequence BCAD</arm_group_label>
    <arm_group_label>Sequence CDBA</arm_group_label>
    <arm_group_label>Sequence DACB</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin placebo</intervention_name>
    <description>Moxifloxacin placebo is available as white, film-coated tablet. containing nonactive material for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water.</description>
    <arm_group_label>Sequence ABDC</arm_group_label>
    <arm_group_label>Sequence BCAD</arm_group_label>
    <arm_group_label>Sequence CDBA</arm_group_label>
    <arm_group_label>Sequence DACB</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female between 18 and 55 years of age, inclusive, at the time of signing the&#xD;
             informed consent&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician, based on a medical&#xD;
             evaluation including medical history, physical examination, laboratory tests, and&#xD;
             cardiac monitoring. A subject with a clinical abnormality or laboratory parameters&#xD;
             outside the reference range for the population being studied may be included only if&#xD;
             the investigator feels and documents that the finding is unlikely to introduce&#xD;
             additional risk factors and will not interfere with the study procedures.&#xD;
&#xD;
          -  Body weight &gt;= 50 kilogram (kg) and body mass index within the range 19 to 31 kilogram&#xD;
             / square meter (kg/m^2) (inclusive).&#xD;
&#xD;
          -  A female subject is eligible to participate if she is not pregnant (as confirmed by a&#xD;
             negative serum beta-human chorionic gonadotrophin test), not lactating, and at least&#xD;
             one of the following conditions applies:&#xD;
&#xD;
          -  Nonreproductive potential defined as:&#xD;
&#xD;
          -  Premenopausal females with one of the following: Documented tubal ligation, documented&#xD;
             hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal&#xD;
             occlusion, hysterectomy, documented bilateral oophorectomy.&#xD;
&#xD;
          -  Postmenopausal defined as 12 months of spontaneous amenorrhea. To confirm&#xD;
             postmenopausal status, a blood sample for simultaneous follicle-stimulating hormone&#xD;
             (FSH) &gt;40 milli-international units per mililiter (mlU/mL) and estradiol &lt;40&#xD;
             picogram/milliliter (pg/mL) (&lt;147 picomole/liter [pmol/L]) is confirmatory. Females on&#xD;
             hormone replacement therapy (HRT) and whose menopausal status is in doubt will be&#xD;
             required to use one of the highly effective contraception methods if they wish to&#xD;
             continue their HRT during the study. Otherwise, they must discontinue HRT to allow&#xD;
             confirmation of postmenopausal status prior to study enrolment.&#xD;
&#xD;
          -  Reproductive potential and agrees to follow one of the options listed below in the GSK&#xD;
             Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of&#xD;
             Reproductive Potential (FRP) requirements from 30 days prior to the first dose of&#xD;
             study drug and until at least 7 days after the last dose of study drug and completion&#xD;
             of the follow-up visit.&#xD;
&#xD;
          -  This list does not apply to FRP with same sex partners, when this is their preferred&#xD;
             and usual lifestyle or for subjects who are and will continue to be abstinent from&#xD;
             penile-vaginal intercourse on a long-term and persistent basis.&#xD;
&#xD;
          -  Contraceptive subdermal implant that meets the standard operating procedure (SOP)&#xD;
             effectiveness criteria including a &lt;1% rate of failure per year, as stated in the&#xD;
             product label, intrauterine device or intrauterine system that meets the SOP&#xD;
             effectiveness criteria including a &lt;1% rate of failure per year, as stated in the&#xD;
             product label, oral contraceptive, either combined or progestogen alone, injectable&#xD;
             progestogen, contraceptive vaginal ring, percutaneous contraceptive patches, male&#xD;
             partner sterilization with documentation of azoospermia prior to the female subject's&#xD;
             entry into the study, and this male is the sole partner for that subject.&#xD;
&#xD;
          -  These allowed methods of contraception are only effective when used consistently,&#xD;
             correctly and in accordance with the product label. The investigator is responsible&#xD;
             for ensuring that subjects understand how to properly use these methods of&#xD;
             contraception.&#xD;
&#xD;
          -  Capable of giving signed informed consent as described in protocol, which includes&#xD;
             compliance with the requirements and restrictions listed in the consent form and in&#xD;
             the protocol&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and bilirubin &lt;1.5 × upper limit of normal range (ULN).&#xD;
             Isolated bilirubin &gt;1.5 × ULN is acceptable if bilirubin is fractionated and direct&#xD;
             bilirubin &lt;35%. One repeat test to confirm result is acceptable.&#xD;
&#xD;
          -  Serum potassium, calcium, and magnesium laboratory parameters within normal limits at&#xD;
             screening and check-in.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History/evidence of any arrhythmia (for example, second- or third-degree heart block,&#xD;
             atrial fibrillation, supraventricular tachycardia, symptomatic sinus bradycardia,&#xD;
             junctional rhythm) or clinically significant cardiac disease or procedure (mitral&#xD;
             valve regurgitation, heart murmur, angina/ischemia, congenital heart abnormalities,&#xD;
             coronary artery bypass grafting surgery, or percutaneous transluminal coronary&#xD;
             angioplasty). A history of additional risk factors for torsades de pointes (e.g.,&#xD;
             heart failure, hypokalemia, and family history of long QT syndrome).&#xD;
&#xD;
          -  Current or chronic history of liver disease or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  Any clinically significant CNS (e.g., seizures), cardiac, pulmonary, metabolic, renal,&#xD;
             hepatic, or GI conditions or history of such conditions that, in the opinion of the&#xD;
             investigator, may place the subject at an unacceptable risk as a participant in this&#xD;
             trial or may interfere with the absorption, distribution, metabolism, or excretion of&#xD;
             drugs.&#xD;
&#xD;
          -  History of photosensitivity to quinolones.&#xD;
&#xD;
          -  Use of systemic antibiotic within 30 days of screening.&#xD;
&#xD;
          -  Confirmed lifetime history of C. difficile diarrhea&#xD;
&#xD;
          -  History of spontaneous tendon rupture&#xD;
&#xD;
          -  History of smoking or use of nicotine containing products within 3 months of screening&#xD;
             or a positive urine cotinine indicative of smoking at screening.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as an&#xD;
             average weekly intake of &gt;14 drinks for males or &gt;7 drinks for females. One drink is&#xD;
             equivalent to 12 grams of alcohol: 12 fluid ounces (fl oz) (360 millilitre [mL]) of&#xD;
             beer, 5 fl oz (150 mL) of wine, or 1.5 fl oz (45 mL) of 80-proof distilled spirits.&#xD;
&#xD;
          -  History of sensitivity to any of the study drugs or components thereof or a history of&#xD;
             drug or other allergy that, in the opinion of the investigator or GSK medical monitor,&#xD;
             contraindicates the potential subject's participation.&#xD;
&#xD;
          -  History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical&#xD;
             research unit uses heparin to maintain IV cannula patency).&#xD;
&#xD;
          -  A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody&#xD;
             result within 3 months of screening or positive human immunodeficiency virus (HIV)&#xD;
             antibody.&#xD;
&#xD;
          -  A positive urine test for drugs of abuse at screening or at Day -1; positive urine&#xD;
             test for alcohol (or alcohol breath test) within 24 hours of any dose in the study.&#xD;
&#xD;
          -  Exclusion criteria for screening and baseline ECG (a single repeat test is allowed for&#xD;
             eligibility determination): Heart rate: &lt;40 and &gt;100 beats per minute (bpm) (For&#xD;
             males), &lt;45 and &gt;100 bpm (For Females); PR interval&lt;120 and &gt;220 millisecond (msec);&#xD;
             QRS duration&lt;70 and &gt;110 msec; QTcF interval&gt;450 msec.&#xD;
&#xD;
          -  Evidence of previous myocardial infarction (does not include ST-segment changes&#xD;
             associated with repolarization).&#xD;
&#xD;
          -  Any conduction abnormality (including but not specific to left or right complete&#xD;
             bundle branch block, atrioventricular block [second degree or higher],&#xD;
             Wolff-Parkinson-White syndrome), sinus pauses &gt;3 seconds, non-sustained or sustained&#xD;
             ventricular tachycardia (&gt;3 consecutive ventricular ectopic beats), or any significant&#xD;
             arrhythmia that, in the opinion of the investigator and GSK medical monitor, will&#xD;
             interfere with the safety of the individual subject.&#xD;
&#xD;
          -  An abnormal finding of clinical significance in the arrhythmia detection Holter&#xD;
             performed on Day -2, which in the view of the investigator would compromise subject&#xD;
             safety or interfere with study procedures or assessments will be excluded from the&#xD;
             study. Full disclosures will be reviewed in detail and the review maintained as part&#xD;
             of the subject's source documents. Analysis of the Holter recordings will consider the&#xD;
             following:&#xD;
&#xD;
          -  Heart rate (significant brady- or tachycardia, based on investigator's judgment)&#xD;
&#xD;
          -  Reports of symptomatic arrhythmia (except isolated extrasystoles)&#xD;
&#xD;
          -  Normal and aberrant beats&#xD;
&#xD;
          -  Number of supraventricular contractions, premature atrial contractions, premature&#xD;
             ventricular contractions, couplets, triplets, and ventricular tachycardias&#xD;
&#xD;
          -  Atrioventricular conduction defects&#xD;
&#xD;
          -  Atrial fibrillation and flutter&#xD;
&#xD;
          -  Participation in the study would result in a donation of blood or blood products in&#xD;
             excess of 500 mL within a 56-day period.&#xD;
&#xD;
          -  Participation in a clinical trial in which the subject has received an investigational&#xD;
             product within the following time period prior to the first dosing day in the current&#xD;
             study: 30 days, 5 half-lives, or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer).&#xD;
&#xD;
          -  Exposure to more than 4 new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>July 10, 2017</last_update_submitted>
  <last_update_submitted_qc>July 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TQTc</keyword>
  <keyword>Moxifloxacin</keyword>
  <keyword>GSK2140944</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Tract Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>Gepotidacin</mesh_term>
    <mesh_term>Norgestimate, ethinyl estradiol drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>115775</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT02257398
org study id: 115775
nct id: NCT02257398
lead sponsor: 
has dmc: No
This is Phase I, 4-period, randomized, active-and placebo-controlled, double-blind crossover,
      single-dose study to evaluate the effects of a therapeutic (1000 milligram [mg]) and
      supratherapeutic (1800 mg) dose of GSK2140944 with a positive control (moxifloxacin 400 mg)
      and placebo on the corrected QT interval (QTc) as assessed by continuous 12-lead Holter
      electrocardiograms (ECGs) in approximately 55 healthy volunteers.

      All subjects will receive single doses of GSK2140944 1000 mg, GSK2140944 1800 mg,
      moxifloxacin 400 mg, and placebo in a randomized sequence. A double-dummy approach will be
      used to maintain blinding. Thus, on each dosing day, moxifloxacin or moxifloxacin placebo and
      GSK2140944 or placebo will be administered.

      Subjects will be screened within 30 days prior to entry to the clinic. Subjects will report
      to the clinical unit on Day -2 of Period 1 and on Day -1 in subsequent periods. Subjects will
      remain confined until check out procedures have been completed on Day 3 (5 days confinement
      in Period 1 and 4 days in the following 3 periods). There will be a washout of at least 7
      days between doses. The follow-up visit will occur 7-10 days after the final dose. Total
      duration of the study (from screening to the follow-up visit) will be approximately 60 days.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in corrected QT interval, using the Fridericia formula (QTcF) for GSK2140944 (1000 mg and 1800 mg)
time frame: Up to 48 hours
description: ECGs will be measured using a 24-hour continuous 12-lead Holter monitor. ECGs will be extracted up to 10 replicates at the following time points: at 3 time points pre-dose (45, 30, and 15 minutes prior to starting the infusion) and 0.25, 0.5, 1.0, 1.5, 2.0 (end of infusion), 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24 and 48 hours after dosing, for a total of 16 time points per treatment period
measure: Change from baseline in ECG parameters for GSK2140944 (1000 mg and 1800 mg)
time frame: Up to 48 hours
description: ECGs will be measured using a 24-hour continuous 12-lead Holter monitor at predefined timepoints. ECG parameters includes QT (QT interval), QT corrected according to the Bazett formula (QTcB), QT/RR pairs from the defined time points at which subjects are supinely resting (QTci), Individually corrected QT interval (QTcI), heart rate (HR), PR interval, and the complex of 3 of the graphical deflections seen on a typical ECG (QRS) interval
measure: Categorical outliers in ECG parameters for GSK2140944 (1000 mg and 1800 mg)
time frame: Up to 48 hours
description: ECGs will be measured using a 24-hour continuous 12-lead Holter monitor at predefined time points. Categorical outliers ECG parameters includes QTc, HR, PR, and QRS interval
measure: Change from baseline in ECG parameters for moxifloxacin
time frame: Up to 48 hours
description: ECGs will be measured using a 24-hour continuous 12-lead Holter monitor at predefined time points. ECG parameters includes QTcF, QTcB, QTci, QTcI, QT, HR, PR, and QRS interval
measure: Composite of pharmacokinetic (PK) parameters for GSK2140944 (1000 mg and 1800 mg)
time frame: Up to 48 hours
description: PK parameters including area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]), area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration (AUC[0-t]), systemic clearance of parent drug (CL), maximum observed concentration (Cmax)
measure: Composite of PK parameters for moxifloxacin
time frame: Up to 48 hours
description: PK parameters including AUC(0-infinity), AUC(0-t), CL, apparent clearance of parent drug after oral dosing (CL/F), Cmax, λz, t1/2, tmax, Vss, Vz, apparent volume of distribution after oral dosing (Vz/F).
measure: Plasma concentrations and change in QTcF for GSK2140944 and moxifloxacin
time frame: Up to 48 hours
description: The relationship between GSK2140944 plasma concentration following single IV administration and the baseline adjusted QTcF interval corrected for placebo will be explored
measure: Amount excreted (Ae) in urine of unchanged GSK2140944 (1000 mg and 1800 mg)
time frame: Up to 48 hours
description: Urinary recovery of unchanged drug that is total amount of drug excreted in urine (Ae), calculated by adding all the fractions of drug collected over all the allotted time intervals
measure: Fraction of the dose (fe) excreted in urine
time frame: Up to 48 hours
description: Fraction of the dose (fe) will be calculated as, percentage fe= (Ae/Dose) × 100
measure: Renal clearance
time frame: Up to 48 hours
description: Renal clearance of drug will be calculated as: Ae/ AUC(0-t)
measure: Assessment of ECG
time frame: Up to Day 48
description: Single 12-lead safety ECGs will be obtained at predefined time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals
measure: Change from baseline in vital sign measurements
time frame: Up to Day 48
description: Vital signs includes temperature, systolic and diastolic blood pressure and pulse rate and respiratory rate
measure: Number of subjects with adverse events (AEs)
time frame: Up to Day 48
description: An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
measure: Toxicity grading of clinical laboratory test results
time frame: Up to Day 48
description: Clinical laboratory parameters includes hematology, clinical chemistry, and urinalysis
arm group label: Sequence ABDC
arm group type: Experimental
description: Subjects will be administered treatments in Sequence ABDC where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes
arm group label: Sequence BCAD
arm group type: Experimental
description: Subjects will be administered treatments in Sequence BCAD where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes
arm group label: Sequence CDBA
arm group type: Experimental
description: Subjects will be administered treatments in Sequence CDBA where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes
arm group label: Sequence DACB
arm group type: Experimental
description: Subjects will be administered treatments in Sequence DACB where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes
intervention type: Drug
intervention name: GSK2140944
description: GSK2140944 is available in dose strength 1000 mg and 1800 mg for single IV dose over 2 hours administration as a pale yellow to greyish yellow cake for reconstitution
arm group label: Sequence ABDC
arm group label: Sequence BCAD
arm group label: Sequence CDBA
arm group label: Sequence DACB
intervention type: Drug
intervention name: GSK2140944 placebo
description: GSK2140944 placebo is 0.9% sodium chloride available for single IV dose over 2 hours administration.
arm group label: Sequence ABDC
arm group label: Sequence BCAD
arm group label: Sequence CDBA
arm group label: Sequence DACB
intervention type: Drug
intervention name: Moxifloxacin
description: Moxifloxacin is available as pinkish red tablet with dose strength 400 mg for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water.
arm group label: Sequence ABDC
arm group label: Sequence BCAD
arm group label: Sequence CDBA
arm group label: Sequence DACB
intervention type: Drug
intervention name: Moxifloxacin placebo
description: Moxifloxacin placebo is available as white, film-coated tablet. containing nonactive material for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water.
arm group label: Sequence ABDC
arm group label: Sequence BCAD
arm group label: Sequence CDBA
arm group label: Sequence DACB
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Tract Infections
mesh term: Moxifloxacin
mesh term: Gepotidacin
mesh term: Norgestimate, ethinyl estradiol drug combination
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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