<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/NCT01702376</url>
  </required_header>
  <id_info>
    <org_study_id>113789</org_study_id>
    <nct_id>NCT01702376</nct_id>
  </id_info>
  <brief_title>This Study Will Investigate the Effect of Single Oral Doses of Retosiban on Cardiac Repolarization, With Moxifloxacin as a Positive Control in Healthy Volunteers.</brief_title>
  <official_title>A Randomized, Placebo-Controlled, Double-Blind, Four-way Crossover Study to Assess the Effect of Single Oral Doses of Retosiban on Cardiac Repolarization, With Moxifloxacin as a Positive Control 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 will be a randomized, placebo-controlled, single, oral dose, four-way Williams crossover&#xD;
      study design in healthy male and female subjects. The study consists of screening (28 days),&#xD;
      treatment (1 day/dosing session) and follow-up (7 to 14 days) period and the total duration&#xD;
      of study participation for each subject will be approximately 9 weeks. Each subject will&#xD;
      participate in 4 dosing sessions separated by a minimum 7-day washout period. All subjects&#xD;
      will receive single doses of retosiban 100 mg, (treatment A) retosiban 800 mg (Treatment B),&#xD;
      moxifloxacin 400 mg (Treatment C) and placebo (Treatment D) in one of the four treatment&#xD;
      sequences (ABDC, BCAD, CDBA, DACB) following a Williams design Twelve-lead ECGs and&#xD;
      continuous Holter monitoring, clinical laboratory safety tests, vital sign measurements,&#xD;
      physical examinations, adverse event reports, and pharmacokinetic samples will be collected&#xD;
      throughout the study. In each study period, cardiac conduction will be measured using a&#xD;
      24-hour continuous 12-lead Holter monitor from the morning of Day 1 (dosing) until the&#xD;
      morning of Day 2.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 3, 2012</start_date>
  <completion_date type="Actual">January 14, 2013</completion_date>
  <primary_completion_date type="Actual">January 14, 2013</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 QT duration corrected for heart rate by Fridericia's formula (QTcF) interval at each timepoint for retosiban as compared with time-matched placebo</measure>
    <time_frame>Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session.</time_frame>
    <description>Single 12-lead electrocardiograms (ECG)s will be obtained at each timepoint during the study using an ECG machine that automatically calculates corrected QT interval (QTc) interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF, QT duration corrected for heart rate by Bazett's formula (QTcB), and QT interval corrected for heart rate (QTci) /QTciL interval at each timepoint for 100 mg and 800 mg retosiban as compared with time-matched placebo</measure>
    <time_frame>Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session.</time_frame>
    <description>Single 12-lead ECGs will be obtained for subjects receiving 100 mg and 800 mg retosiban at each timepoint during the study using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF, QTcB, and QTci/QTciL interval at each timepoint for moxifloxacin as compared with time-matched placebo</measure>
    <time_frame>Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session.</time_frame>
    <description>Single 12-lead ECGs will be obtained for subjects receiving moxifloxacin at each timepoint during the study using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations of retosiban and GSK2847065</measure>
    <time_frame>Day 1 (pre-dose), 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose and Day 2 per dosing session.</time_frame>
    <description>Pharmacokinetic data will include plasma concentration of retosiban and GSK2847065</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax) for retosiban and GSK2847065</measure>
    <time_frame>Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session</time_frame>
    <description>Pharmacokinetic data will include Cmax of retosiban and GSK2847065</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum concentration (tmax) for retosiban and GSK2847065</measure>
    <time_frame>Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session</time_frame>
    <description>Pharmacokinetic data will include tmax of retosiban and GSK2847065</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve over the dosing interval (AUC(0-τ)) for retosiban and GSK2847065</measure>
    <time_frame>Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session</time_frame>
    <description>Pharmacokinetic data will include AUC0-τ of retosiban and GSK2847065</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal change from baseline for QTcF and QTcB</measure>
    <time_frame>Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session</time_frame>
    <description>Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Maximal Change from baseline = maximum 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate at each timepoint</measure>
    <time_frame>Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session</time_frame>
    <description>Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. Change from baseline for other cardiac electrophysiological will be calculated as: other cardiac electrophysiological parameters at each timepoint minus baseline value</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of retosiban as assessed by change from baseline in 12-lead ECGs</measure>
    <time_frame>Day 1 (pre-dose, 1 hr, 8 hr, 12 hr post-dose), Day 2 and Day 7</time_frame>
    <description>Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of retosiban as assessed by change from baseline in systolic and diastolic blood pressure</measure>
    <time_frame>Day 1 (pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose), Day 2 and Day 7</time_frame>
    <description>Vital sign measurements will be done in supine position and will include systolic and diastolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of retosiban as assessed by change from baseline in pulse rate</measure>
    <time_frame>Day 1 (pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose), Day 2 and Day 7</time_frame>
    <description>Vital sign measurements will be done in supine position and will include pulse rate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of retosiban as assessed number of adverse events</measure>
    <time_frame>9 weeks</time_frame>
    <description>Safety and tolerability parameters will include recording of AEs, throughout the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of retosiban as assessed by change from baseline in clinical laboratory tests</measure>
    <time_frame>Day -1 and Day 2 and Day 7</time_frame>
    <description>Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Obstetric Labour, Premature</condition>
  <arm_group>
    <arm_group_label>Retosiban 100 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will be randomized to single dose of retosiban 100 mg in one of the four treatment sequences.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Retosiban 800 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will be randomized to single dose of retosiban 800 mg in one of the four treatment sequences</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each subject will be randomized to single dose of matching placebo in one of the four treatment sequences</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxifloxacin 400 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Each subject will be randomized to single dose of moxifloxacin 400 mg in one of the four treatment sequences</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Retosiban 100 mg</intervention_name>
    <description>Subjects will be administered with single dose of one moxifloxacin placebo tablet, one 100 mg tablet of retosiban and 7 retosiban matched placebo tablets</description>
    <arm_group_label>Retosiban 100 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Retosiban 800 mg</intervention_name>
    <description>Subjects will be administered with single dose of one moxifloxacin placebo tablet and eight 100 mg tablets of retosiban</description>
    <arm_group_label>Retosiban 800 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will be administered with one moxifloxacin placebo tablet and eight retosiban matched placebo tablets</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin 400 mg</intervention_name>
    <description>Subjects will be administered with one 400 mg moxifloxacin tablet and eight retosiban matched placebo tablets</description>
    <arm_group_label>Moxifloxacin 400 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  - Male or female between 18 and 45 years of age inclusive, at the time of signing the&#xD;
             informed consent&#xD;
&#xD;
          -  A female subject is eligible to participate if she is of: child-bearing potential and&#xD;
             agrees to use the contraception methods from time of consent until until 48 hours post&#xD;
             last dose; Non-childbearing potential defined as pre-menopausal females with a&#xD;
             documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of&#xD;
             spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose&#xD;
             menopausal status is in doubt will be required to use the contraception methods if&#xD;
             they wish to continue their HRT during the study. Otherwise, they must discontinue HRT&#xD;
             to allow confirmation of post-menopausal status prior to study enrollment. For most&#xD;
             forms of HRT, at least 2 to 4 weeks should elapse between the cessation of therapy and&#xD;
             the blood draw; this interval depends on the type and dosage of HRT. Following&#xD;
             confirmation of their post-menopausal status, they can resume use of HRT during the&#xD;
             study without use of a contraceptive method.&#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 and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding&#xD;
             is unlikely to introduce additional risk factors and will not interfere with the study&#xD;
             procedures.&#xD;
&#xD;
          -  Body weight (greater than or equal to) &gt;=50 kg and body mass index (BMI) within the&#xD;
             range 19 to 29.9 kg/m^2&#xD;
&#xD;
          -  Capable of giving written informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the consent form&#xD;
&#xD;
          -  No significant abnormality on 12-lead ECG at screening, including the following&#xD;
             specific requirements: ventricular rate &gt;=40 beats per minute, PR interval less than&#xD;
             or equal to (&lt;=) 210 miliseconds (msec), Q waves less than (&lt;)30 msec, QRS interval to&#xD;
             be &gt;=60 msec and &lt;120 msec; the waveforms must enable the QT interval to be clearly&#xD;
             defined; QTcB or QTcF interval must be &lt;450 msec&#xD;
&#xD;
          -  ALT, alkaline phosphatase and bilirubin &lt;=1.5xULN (isolated bilirubin greater than (&gt;)&#xD;
             1.5x upper limit of normal (ULN) is acceptable if bilirubin is fractionated and direct&#xD;
             bilirubin &lt;35%)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result within 3 months of screening.&#xD;
&#xD;
          -  A supine blood pressure that is persistently higher than 140/90 millimeters of mercury&#xD;
             (mmHg).&#xD;
&#xD;
          -  A supine mean heart rate outside the range 40 to 90 beats per minute (bpm).&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  A positive test for Human Immunodeficiency Virus (HIV) antibody.&#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 g of alcohol: 12 ounces (360 ml [milliliters]) of beer, 5 ounces (150&#xD;
             ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.&#xD;
&#xD;
          -  The subject has participated in a clinical trial and 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 four new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, or components thereof or a&#xD;
             history of drug or other allergy that, in the opinion of the investigator or GSK&#xD;
             Medical Monitor, contraindicates their participation.&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 ml within a 56 day period.&#xD;
&#xD;
          -  Pregnant females as determined by positive serum human chorionic gonadotropin (hCG)&#xD;
             test at screening or prior to dosing. Lactating females.&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol.&#xD;
&#xD;
          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or&#xD;
             nicotine-containing products within 6 months prior to screening.&#xD;
&#xD;
          -  Unable to refrain from consumption of red wine, seville oranges, grapefruit or&#xD;
             grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit&#xD;
             juices from 7 days prior to the first dose of study medication.&#xD;
&#xD;
          -  History or presence of any medically significant disease, or any disorder that would&#xD;
             introduce additional risk or interfere with the study procedures or outcome. In&#xD;
             particular, a family history of QT prolongation, of early or sudden cardiac death or&#xD;
             of early cardiovascular disease.&#xD;
&#xD;
          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary&#xD;
             supplements from 14 days before screening until the follow-up visit unless in the&#xD;
             opinion of the Investigator and sponsor the medication will not interfere with the&#xD;
             study or compromise subject safety.&#xD;
&#xD;
          -  Serum calcium, magnesium or potassium levels outside the reference range&#xD;
&#xD;
          -  History of sensitivity to quinolone antibiotics 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 their participation.&#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>
  <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>Baltimore</city>
        <state>Maryland</state>
        <zip>21225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.clinicalstudydatarequest.com</url>
    <description>Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.</description>
  </link>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <last_update_submitted>June 9, 2017</last_update_submitted>
  <last_update_submitted_qc>June 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obstetric Labor, Premature</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</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>113789</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>113789</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>113789</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>113789</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_doc>
      <doc_id>113789</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>113789</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>113789</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_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/NCT01702376
org study id: 113789
nct id: NCT01702376
lead sponsor: 
has dmc: No
This will be a randomized, placebo-controlled, single, oral dose, four-way Williams crossover
      study design in healthy male and female subjects. The study consists of screening (28 days),
      treatment (1 day/dosing session) and follow-up (7 to 14 days) period and the total duration
      of study participation for each subject will be approximately 9 weeks. Each subject will
      participate in 4 dosing sessions separated by a minimum 7-day washout period. All subjects
      will receive single doses of retosiban 100 mg, (treatment A) retosiban 800 mg (Treatment B),
      moxifloxacin 400 mg (Treatment C) and placebo (Treatment D) in one of the four treatment
      sequences (ABDC, BCAD, CDBA, DACB) following a Williams design Twelve-lead ECGs and
      continuous Holter monitoring, clinical laboratory safety tests, vital sign measurements,
      physical examinations, adverse event reports, and pharmacokinetic samples will be collected
      throughout the study. In each study period, cardiac conduction will be measured using a
      24-hour continuous 12-lead Holter monitor from the morning of Day 1 (dosing) until the
      morning of Day 2.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in QT duration corrected for heart rate by Fridericia's formula (QTcF) interval at each timepoint for retosiban as compared with time-matched placebo
time frame: Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session.
description: Single 12-lead electrocardiograms (ECG)s will be obtained at each timepoint during the study using an ECG machine that automatically calculates corrected QT interval (QTc) interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading.
measure: Change from baseline in QTcF, QT duration corrected for heart rate by Bazett's formula (QTcB), and QT interval corrected for heart rate (QTci) /QTciL interval at each timepoint for 100 mg and 800 mg retosiban as compared with time-matched placebo
time frame: Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session.
description: Single 12-lead ECGs will be obtained for subjects receiving 100 mg and 800 mg retosiban at each timepoint during the study using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading
measure: Change from baseline in QTcF, QTcB, and QTci/QTciL interval at each timepoint for moxifloxacin as compared with time-matched placebo
time frame: Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session.
description: Single 12-lead ECGs will be obtained for subjects receiving moxifloxacin at each timepoint during the study using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading.
measure: Plasma concentrations of retosiban and GSK2847065
time frame: Day 1 (pre-dose), 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose and Day 2 per dosing session.
description: Pharmacokinetic data will include plasma concentration of retosiban and GSK2847065
measure: Maximum observed concentration (Cmax) for retosiban and GSK2847065
time frame: Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session
description: Pharmacokinetic data will include Cmax of retosiban and GSK2847065
measure: Time to maximum concentration (tmax) for retosiban and GSK2847065
time frame: Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session
description: Pharmacokinetic data will include tmax of retosiban and GSK2847065
measure: Area under the concentration-time curve over the dosing interval (AUC(0-τ)) for retosiban and GSK2847065
time frame: Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session
description: Pharmacokinetic data will include AUC0-τ of retosiban and GSK2847065
measure: Maximal change from baseline for QTcF and QTcB
time frame: Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session
description: Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Maximal Change from baseline = maximum 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading
measure: Change from baseline for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate at each timepoint
time frame: Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session
description: Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. Change from baseline for other cardiac electrophysiological will be calculated as: other cardiac electrophysiological parameters at each timepoint minus baseline value
measure: Safety and tolerability of retosiban as assessed by change from baseline in 12-lead ECGs
time frame: Day 1 (pre-dose, 1 hr, 8 hr, 12 hr post-dose), Day 2 and Day 7
description: Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals
measure: Safety and tolerability of retosiban as assessed by change from baseline in systolic and diastolic blood pressure
time frame: Day 1 (pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose), Day 2 and Day 7
description: Vital sign measurements will be done in supine position and will include systolic and diastolic blood pressure
measure: Safety and tolerability of retosiban as assessed by change from baseline in pulse rate
time frame: Day 1 (pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose), Day 2 and Day 7
description: Vital sign measurements will be done in supine position and will include pulse rate.
measure: Safety and tolerability of retosiban as assessed number of adverse events
time frame: 9 weeks
description: Safety and tolerability parameters will include recording of AEs, throughout the study
measure: Safety and tolerability of retosiban as assessed by change from baseline in clinical laboratory tests
time frame: Day -1 and Day 2 and Day 7
description: Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
arm group label: Retosiban 100 mg
arm group type: Experimental
description: Each subject will be randomized to single dose of retosiban 100 mg in one of the four treatment sequences.
arm group label: Retosiban 800 mg
arm group type: Experimental
description: Each subject will be randomized to single dose of retosiban 800 mg in one of the four treatment sequences
arm group label: Placebo
arm group type: Placebo Comparator
description: Each subject will be randomized to single dose of matching placebo in one of the four treatment sequences
arm group label: Moxifloxacin 400 mg
arm group type: Active Comparator
description: Each subject will be randomized to single dose of moxifloxacin 400 mg in one of the four treatment sequences
intervention type: Drug
intervention name: Retosiban 100 mg
description: Subjects will be administered with single dose of one moxifloxacin placebo tablet, one 100 mg tablet of retosiban and 7 retosiban matched placebo tablets
arm group label: Retosiban 100 mg
intervention type: Drug
intervention name: Retosiban 800 mg
description: Subjects will be administered with single dose of one moxifloxacin placebo tablet and eight 100 mg tablets of retosiban
arm group label: Retosiban 800 mg
intervention type: Drug
intervention name: Placebo
description: Subjects will be administered with one moxifloxacin placebo tablet and eight retosiban matched placebo tablets
arm group label: Placebo
intervention type: Drug
intervention name: Moxifloxacin 400 mg
description: Subjects will be administered with one 400 mg moxifloxacin tablet and eight retosiban matched placebo tablets
arm group label: Moxifloxacin 400 mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United States
url: https://www.clinicalstudydatarequest.com
description: Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
responsible party type: Sponsor
mesh term: Obstetric Labor, Premature
mesh term: Moxifloxacin
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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