<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/NCT01669083</url>
  </required_header>
  <id_info>
    <org_study_id>116741</org_study_id>
    <nct_id>NCT01669083</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Pharmacokinetics, Safety and Tolerability of GSK557296 in Healthy Women Volunteers After Single and Repeat Dosing</brief_title>
  <official_title>A Phase I Non-Randomized Multi Cohort, Open Label, Bridging Study to Evaluate the Pharmacokinetics, Safety and Tolerability of GSK557296 in Healthy Women Volunteers After Single and Repeat Dosing</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>
      GSK557296 is being studied in women for the indication of enhanced embryo and or blastocyst&#xD;
      implantation in women undergoing IVF treatment. This study will be the first dosing&#xD;
      experience with this compound in women. It is important to characterize the pharmacokinetics&#xD;
      of GSK557296 in women to determine the most appropriate doses and dosing regimens for future&#xD;
      clinical studies. Understanding the pharmacokinetics of GSK557296 in women will also enable&#xD;
      more accurate characterization of any exposure-response relationship in future studies.&#xD;
&#xD;
      Two previous studies with GSK557296 were conducted in men with oral doses ranging from 10&#xD;
      milligram (mg) to 200 mg. GSK557296 is being studied in women for the indication of enhanced&#xD;
      embryo and or blastocyst implantation in women undergoing IVF treatment. This is a bridging&#xD;
      study to characterize the pharmacokinetics of GSK557296 in women to determine the most&#xD;
      appropriate doses and dosing regimens for future clinical studies.&#xD;
&#xD;
      This is a non-randomized, open label, adaptive design study in healthy female volunteers. A&#xD;
      maximum total of 48 subjects, will participate in different cohorts. Subjects in Cohort 1&#xD;
      will receive 10 mg single dose followed by repeat dose. A one week break will occur to allow&#xD;
      for analysis of the PK data, prior to starting the second Cohort. Subjects in Cohort 2 will&#xD;
      receive 150 mg single dose followed by repeat dose. Cohort 3 and Cohort 4 were adaptive based&#xD;
      on the requirement of additional doses to be studies after PK data will be analyzed from each&#xD;
      of the first 2 cohorts.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 16, 2012</start_date>
  <completion_date type="Actual">March 9, 2013</completion_date>
  <primary_completion_date type="Actual">March 9, 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of PK parameters of 20 mg GSK557296 following single and repeat oral dosing</measure>
    <time_frame>7 days</time_frame>
    <description>From the plasma concentration-time data, the following PK parameters will be determined: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2). AUC(0-infinity) or AUC(0-τ) and Cmax following single and repeat doses may be used for assessment of dose proportionality.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite of PK parameters of 150 mg GSK557296 following single and repeat oral dosing</measure>
    <time_frame>14 days</time_frame>
    <description>From the plasma concentration-time data, the following PK parameters will be determined: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2). AUC(0- infinity) or AUC(0-τ) and Cmax following single and repeat doses may be used for assessment of dose proportionality.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK557296 following single and repeat dosing</measure>
    <time_frame>up to 49 days</time_frame>
    <description>Safety and tolerability parameters assessments include adverse events, clinical laboratory, ECG, vital signs, and concurrent medication</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Embryo Transfer</condition>
  <arm_group>
    <arm_group_label>Cohort 1: GSK557296 10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK557296 10 mg single dose on Day 1 followed by repeat dosing (4 times a day) on Days 2-6</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: GSK557296 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK557296 150 mg as a single dose on Day 1 followed by repeat nominal dosing of the same dose (either 2, 3 or 4 times a day based on half-life demonstrated in treatment A) on Days 9-13</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This study had an adaptive design and additional cohorts may be added depending on the PK profiles of Cohort 1 and Cohort 2. Subjects in this optional Cohort 3 will receive GSK557296 (dose to be determined) as a single dose on Day 1 followed by repeat nominal dosing of the same dose (either 2, 3 or 4 times a day based on half-life demonstrated in Cohort 1 and Cohort 2) on Days 2-6</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This study had an adaptive design and additional cohorts may be added depending on the PK profiles of Cohort 1 and Cohort 1. Subjects in this optional Cohort 4 will receive GSK557296 (dose to be determined) by PK of prior doses, 10-150 mg single dose on Day 1 followed by repeat dosing (either 2, 3 or 4 times a day dependent on half-life demonstrated in prior groups) on Days 2-6</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK557296 10 mg</intervention_name>
    <description>10 mg single oral dose. Each subject will receive 2 tablets of 5 mg GSK557296 four times a day (QID).</description>
    <arm_group_label>Cohort 1: GSK557296 10 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK557296 150 mg</intervention_name>
    <description>150 mg single oral dose. Each subject will receive multiple tablets of 25 mg GSK557296 either 2, 3 or 4 times a day.</description>
    <arm_group_label>Cohort 2: GSK557296 150 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK557296 dose 3</intervention_name>
    <description>Dose to be determined as a single dose tablet based on half-life demonstrated in Cohort 1 and Cohort 2.</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK557296 dose 4</intervention_name>
    <description>Dose to be determined by PK of prior doses, based on half-life demonstrated in prior cohorts.</description>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin &lt;=1.5xupper limit&#xD;
             of normal (ULN)&#xD;
&#xD;
          -  Single or QTcF &lt; 450 millisecond (msec); or QTc &lt; 480 msec in subjects with Bundle&#xD;
             Branch Block&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician&#xD;
&#xD;
          -  Female between 18 and 45 years of age inclusive, at the time of signing the informed&#xD;
             consent&#xD;
&#xD;
          -  A female subject is eligible to participate if she is of Child-bearing potential and&#xD;
             is abstinent or agrees to use contraception methods to sufficiently minimize the risk&#xD;
             of pregnancy during the study.&#xD;
&#xD;
          -  Body weight &gt;= 50 kilogram (kg) and Body Mass Index (BMI) within the range 19 to 29.9&#xD;
             kg per meter^2 (inclusive)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result at screening or within 3 months of screening&#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 or alcohol screen&#xD;
&#xD;
          -  A positive test for HIV antibody&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study&#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), exposure to more than four new chemical&#xD;
             entities within 12 months prior to the first dosing day Unable to refrain from the use&#xD;
             of prescription or non-prescription drugs, with the exception of Oral contraceptives,&#xD;
             within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study&#xD;
             medication history of sensitivity to any of the study medications, or components&#xD;
             thereof or a history of drug or other allergy that, in the opinion of the investigator&#xD;
             or GSK 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 milliliter (mL) within a 56 day period&#xD;
&#xD;
          -  Pregnant females&#xD;
&#xD;
          -  Lactating females&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol&#xD;
&#xD;
          -  Subject is mentally or legally incapacitated&#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 pomelos, exotic citrus fruits, grapefruit hybrids or fruit&#xD;
             juices from 7 days prior to the first dose of study medication&#xD;
      </textblock>
    </criteria>
    <gender>Female</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>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>June 6, 2017</last_update_submitted>
  <last_update_submitted_qc>June 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oxytocin Antagonist</keyword>
  <keyword>Embryo/Blastocyst Implantation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diketopiperazines</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>116741</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>116741</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>116741</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>116741</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>116741</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>116741</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>116741</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_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/NCT01669083
org study id: 116741
nct id: NCT01669083
lead sponsor: 
has dmc: No
GSK557296 is being studied in women for the indication of enhanced embryo and or blastocyst
      implantation in women undergoing IVF treatment. This study will be the first dosing
      experience with this compound in women. It is important to characterize the pharmacokinetics
      of GSK557296 in women to determine the most appropriate doses and dosing regimens for future
      clinical studies. Understanding the pharmacokinetics of GSK557296 in women will also enable
      more accurate characterization of any exposure-response relationship in future studies.

      Two previous studies with GSK557296 were conducted in men with oral doses ranging from 10
      milligram (mg) to 200 mg. GSK557296 is being studied in women for the indication of enhanced
      embryo and or blastocyst implantation in women undergoing IVF treatment. This is a bridging
      study to characterize the pharmacokinetics of GSK557296 in women to determine the most
      appropriate doses and dosing regimens for future clinical studies.

      This is a non-randomized, open label, adaptive design study in healthy female volunteers. A
      maximum total of 48 subjects, will participate in different cohorts. Subjects in Cohort 1
      will receive 10 mg single dose followed by repeat dose. A one week break will occur to allow
      for analysis of the PK data, prior to starting the second Cohort. Subjects in Cohort 2 will
      receive 150 mg single dose followed by repeat dose. Cohort 3 and Cohort 4 were adaptive based
      on the requirement of additional doses to be studies after PK data will be analyzed from each
      of the first 2 cohorts.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Composite of PK parameters of 20 mg GSK557296 following single and repeat oral dosing
time frame: 7 days
description: From the plasma concentration-time data, the following PK parameters will be determined: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2). AUC(0-infinity) or AUC(0-τ) and Cmax following single and repeat doses may be used for assessment of dose proportionality.
measure: Composite of PK parameters of 150 mg GSK557296 following single and repeat oral dosing
time frame: 14 days
description: From the plasma concentration-time data, the following PK parameters will be determined: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-infinity)], and apparent terminal phase half-life (t1/2). AUC(0- infinity) or AUC(0-τ) and Cmax following single and repeat doses may be used for assessment of dose proportionality.
measure: Safety and tolerability of GSK557296 following single and repeat dosing
time frame: up to 49 days
description: Safety and tolerability parameters assessments include adverse events, clinical laboratory, ECG, vital signs, and concurrent medication
arm group label: Cohort 1: GSK557296 10 mg
arm group type: Experimental
description: GSK557296 10 mg single dose on Day 1 followed by repeat dosing (4 times a day) on Days 2-6
arm group label: Cohort 2: GSK557296 150 mg
arm group type: Experimental
description: GSK557296 150 mg as a single dose on Day 1 followed by repeat nominal dosing of the same dose (either 2, 3 or 4 times a day based on half-life demonstrated in treatment A) on Days 9-13
arm group label: Cohort 3
arm group type: Experimental
description: This study had an adaptive design and additional cohorts may be added depending on the PK profiles of Cohort 1 and Cohort 2. Subjects in this optional Cohort 3 will receive GSK557296 (dose to be determined) as a single dose on Day 1 followed by repeat nominal dosing of the same dose (either 2, 3 or 4 times a day based on half-life demonstrated in Cohort 1 and Cohort 2) on Days 2-6
arm group label: Cohort 4
arm group type: Experimental
description: This study had an adaptive design and additional cohorts may be added depending on the PK profiles of Cohort 1 and Cohort 1. Subjects in this optional Cohort 4 will receive GSK557296 (dose to be determined) by PK of prior doses, 10-150 mg single dose on Day 1 followed by repeat dosing (either 2, 3 or 4 times a day dependent on half-life demonstrated in prior groups) on Days 2-6
intervention type: Drug
intervention name: GSK557296 10 mg
description: 10 mg single oral dose. Each subject will receive 2 tablets of 5 mg GSK557296 four times a day (QID).
arm group label: Cohort 1: GSK557296 10 mg
intervention type: Drug
intervention name: GSK557296 150 mg
description: 150 mg single oral dose. Each subject will receive multiple tablets of 25 mg GSK557296 either 2, 3 or 4 times a day.
arm group label: Cohort 2: GSK557296 150 mg
intervention type: Drug
intervention name: GSK557296 dose 3
description: Dose to be determined as a single dose tablet based on half-life demonstrated in Cohort 1 and Cohort 2.
arm group label: Cohort 3
intervention type: Drug
intervention name: GSK557296 dose 4
description: Dose to be determined by PK of prior doses, based on half-life demonstrated in prior cohorts.
arm group label: Cohort 4
criteria: 
gender: Female
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: Diketopiperazines
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.
study doc: 
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