<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/NCT01711463</url>
  </required_header>
  <id_info>
    <org_study_id>115199</org_study_id>
    <nct_id>NCT01711463</nct_id>
  </id_info>
  <brief_title>Relovair PD PK in Chinese Healthy Subjects</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Four-way Crossover Study to Evaluate and Compare the Pharmacodynamics and Pharmacokinetics of Fluticasone Furoate /Vilanterol in Different Dose Combination (50/25mcg, 100/25mcg and 200/25mcg) After Single and Repeat Dose Administration From a Novel Dry Powder Device in Healthy Chinese Subjects</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>
      In this study, fluticasone furoate (FF) and vilanterol (VI) in different dose combinations&#xD;
      (50/25mcg, 100/25mcg and 200/25mcg) will be administered from a single dry powder device to&#xD;
      evaluate the PD, PK, safety and tolerability of the combination in healthy Chinese subjects.&#xD;
      The information gathered will be used as a support of the clinical development program of the&#xD;
      fixed dose combination of FF/VI inhalation powder in Chinese population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single centre, double-blind, placebo-controlled, four-way cross over, randomized,&#xD;
      single and repeat dose study. A total of 16 healthy subjects aged 18-45 years will be&#xD;
      randomised with the aim of achieving at least 10 evaluable subjects to each treatment period.&#xD;
      The primary objective is to evaluate the systemic steroid PD effects (serum cortisol 24 hour&#xD;
      weighted mean on Day 7) of FF and systemic ß-adrenergic PD effects (ECG maximum QTcF 0-4h and&#xD;
      whole blood potassium 0-4h in Day 1 and Day 7) of VI; the secondary objectives are aimed to&#xD;
      evaluate the PK, safety and tolerability of FF/VI inhalation powder after a single and repeat&#xD;
      dose administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 5, 2012</start_date>
  <completion_date type="Actual">June 4, 2013</completion_date>
  <primary_completion_date type="Actual">June 4, 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>Systemic steroid PD effects</measure>
    <time_frame>Day 7</time_frame>
    <description>Serum cortisol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systemic ß-adrenergic PD effects</measure>
    <time_frame>Day 1 and Day 7</time_frame>
    <description>Maximum QTcF 0-4h and whole blood potassium</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations and derived PK parameters for FF/VI</measure>
    <time_frame>Pre-dose, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 4h post dose on Day 1 and pre-dose, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h and 24h post dose on Day 7 and 8.</time_frame>
    <description>Single dose: Cmax, tmax, t1/2, AUC(0-t) (AUC from zero to the last quantifiable timepoint) and AUC(0-t') (AUC from zero to the last common quantifiable timepoint in the dose group). Repeat dose: FF: Cmax, tmax, t1/2, AUC(0-t) and AUC(0-t'), Ro and RCmax, Css_min and AUCss , Css_av, DF; VI: Cmax, tmax, t1/2, AUC(0-t) and AUC(0-t')</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital signs</measure>
    <time_frame>Screening Visit, Day 1, Day 7 and Follow-up Visit</time_frame>
    <description>blood pressure and heart rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-lead ECG</measure>
    <time_frame>Screening Visit, Day 1, Day 7 and Follow-up Visit</time_frame>
    <description>12-lead ECG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory tests</measure>
    <time_frame>Screening Visit, Day 8 of treatment period 4 or early withdrawal Visit and/or follow-up Visit</time_frame>
    <description>Clinical chemistry, hematology and urinalysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>From the start of dosing with investigational product and until the follow-up visit.</time_frame>
    <description>adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>FF/VI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50/25 mcg, 100/25 mcg or 200/25 mcg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>matching placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone Furoate/Vilanterol</intervention_name>
    <description>50/25 or 100/25 or 200/25 mcg inhaled once daily for 7 days in each treatment period.</description>
    <arm_group_label>FF/VI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo inhaled once daily for 7 days in each treatment period.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  AST, ALT, alkaline phosphatase and bilirubin &lt;= 1.5xULN (isolated bilirubin &gt;1.5xULN&#xD;
             is acceptable if bilirubin is fractionated and direct bilirubin &lt;35%).&#xD;
&#xD;
          -  Healthy male or female between 18 and 45 years of age inclusive.&#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 GSK Medical Monitor agree that the finding is unlikely to&#xD;
             introduce additional risk factors and will not interfere with the study procedures.&#xD;
             Subjects with blood pressure values outside the normal range [systolic (90-139 mmHg)&#xD;
             and diastolic (50-89 mmHg)] and subjects with ECG findings suggestive of a previous MI&#xD;
             should always be excluded from enrollment.&#xD;
&#xD;
          -  A female subject is eligible to participate if she is of:&#xD;
&#xD;
        Non-childbearing potential defined as pre-menopausal females with a documented tubal&#xD;
        ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea&#xD;
        [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)&#xD;
        &gt; 40 MlU/ml and estradiol &lt; 40 pg/ml (&lt;147 pmol/L) is confirmatory].&#xD;
&#xD;
        Child-bearing potential and agrees to use one of the contraception methods listed in&#xD;
        Section 8.1 for an appropriate period of time (as determined by the product label or&#xD;
        investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy&#xD;
        at that point. Female subjects must agree to use contraception until completion of the&#xD;
        follow-up visit.&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use one of&#xD;
             the contraception methods listed in Section 8.1. This criterion must be followed from&#xD;
             the time of the first dose of study medication until completion of the follow-up&#xD;
             visit.&#xD;
&#xD;
          -  Body weight &gt;= 50 kg and BMI within the range 19 - 24 kg/m2 (inclusive).&#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:&#xD;
&#xD;
        Ventricular rate &gt;= 45 beats per minute; PR interval &lt;=210msec; No pathological Q waves;&#xD;
        QRS interval to be &gt;= 60msec and &lt;=120msec; The waveforms must enable the QT interval to be&#xD;
        clearly defined; QTc interval must be &lt; 450msec (QTcF; machine or manual reading) based on&#xD;
        a single ECG value, or an average from three ECGs obtained over a brief recording period.&#xD;
&#xD;
          -  Subjects who are current non-smokers, who have not used any tobacco products in the 12&#xD;
             month period preceding the screening visit, and have a pack history of &lt;=5 pack years.&#xD;
&#xD;
          -  Subjects who are able to use the inhalation device satisfactorily.&#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;
          -  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 or on admission to the Unit.&#xD;
&#xD;
          -  A positive urinary cotinine test at screening or on admission to the Unit.&#xD;
&#xD;
          -  A positive test for HIV antibody.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as: an&#xD;
             average weekly intake of greater than 21 units or an average daily intake of greater&#xD;
             than 3 units (males) or defined as an average weekly intake of greater than 14 units&#xD;
             or an average daily intake of greater than 2 units (females). One unit is equivalent&#xD;
             to a 285mL glass of full strength beer or 425mL schooner of light beer or 1 (30mL)&#xD;
             measure of spirits or 1 glass (100mL) of wine (NHMRC Guidelines [NHMRC, 2001]).&#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;
          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary&#xD;
             supplements (including St John's Wort) within 7 days (or 14 days if the drug is a&#xD;
             potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first&#xD;
             dose of study medication, unless in the opinion of the Investigator and GSK Medical&#xD;
             Monitor the medication will not interfere with the study procedures or compromise&#xD;
             subject safety.&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, or components (magnesium&#xD;
             stearate and lactose etc.) or a history of drug or other allergy that, in the opinion&#xD;
             of the investigator or GSK Medical Monitor, contraindicates their participation.&#xD;
&#xD;
          -  History of milk protein allergy.&#xD;
&#xD;
          -  History of any adverse reaction including immediate or delayed hypersensitivity to any&#xD;
             ICS, β2-agonist or sympathomimetic drug.&#xD;
&#xD;
          -  Blood donation or sampled as a study subject within three months preceding the first&#xD;
             dose of study drug and blood donation during the entire study.&#xD;
&#xD;
          -  Pregnant females as determined by positive urine pregnancy test at screening or prior&#xD;
             to dosing.&#xD;
&#xD;
          -  Lactating females.&#xD;
&#xD;
          -  Subjects who have suffered an upper or lower respiratory tract infection within 4&#xD;
             weeks of the screening visit.&#xD;
&#xD;
          -  The subject has taken oral corticosteroids less than 8 weeks before the screening&#xD;
             visit.&#xD;
&#xD;
          -  The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before&#xD;
             the screening visit.&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol.&#xD;
&#xD;
          -  Subject is mentally or legally incapacitated.&#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>Beijing</city>
        <zip>100032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</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>July 2017</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>July 24, 2017</last_update_submitted>
  <last_update_submitted_qc>July 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacodynamics</keyword>
  <keyword>Fluticasone furoate (FF)</keyword>
  <keyword>novel dry powder device</keyword>
  <keyword>Safety and tolerability</keyword>
  <keyword>vilanterol(VI)</keyword>
  <keyword>Healthy Chinese subjects</keyword>
  <keyword>Pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</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>115199</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>115199</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>115199</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>115199</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>115199</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>115199</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>115199</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_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/NCT01711463
org study id: 115199
nct id: NCT01711463
lead sponsor: 
has dmc: No
In this study, fluticasone furoate (FF) and vilanterol (VI) in different dose combinations
      (50/25mcg, 100/25mcg and 200/25mcg) will be administered from a single dry powder device to
      evaluate the PD, PK, safety and tolerability of the combination in healthy Chinese subjects.
      The information gathered will be used as a support of the clinical development program of the
      fixed dose combination of FF/VI inhalation powder in Chinese population.
This is a single centre, double-blind, placebo-controlled, four-way cross over, randomized,
      single and repeat dose study. A total of 16 healthy subjects aged 18-45 years will be
      randomised with the aim of achieving at least 10 evaluable subjects to each treatment period.
      The primary objective is to evaluate the systemic steroid PD effects (serum cortisol 24 hour
      weighted mean on Day 7) of FF and systemic ß-adrenergic PD effects (ECG maximum QTcF 0-4h and
      whole blood potassium 0-4h in Day 1 and Day 7) of VI; the secondary objectives are aimed to
      evaluate the PK, safety and tolerability of FF/VI inhalation powder after a single and repeat
      dose administration.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Systemic steroid PD effects
time frame: Day 7
description: Serum cortisol
measure: Systemic ß-adrenergic PD effects
time frame: Day 1 and Day 7
description: Maximum QTcF 0-4h and whole blood potassium
measure: Plasma concentrations and derived PK parameters for FF/VI
time frame: Pre-dose, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 4h post dose on Day 1 and pre-dose, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h and 24h post dose on Day 7 and 8.
description: Single dose: Cmax, tmax, t1/2, AUC(0-t) (AUC from zero to the last quantifiable timepoint) and AUC(0-t') (AUC from zero to the last common quantifiable timepoint in the dose group). Repeat dose: FF: Cmax, tmax, t1/2, AUC(0-t) and AUC(0-t'), Ro and RCmax, Css_min and AUCss , Css_av, DF; VI: Cmax, tmax, t1/2, AUC(0-t) and AUC(0-t')
measure: Vital signs
time frame: Screening Visit, Day 1, Day 7 and Follow-up Visit
description: blood pressure and heart rate
measure: 12-lead ECG
time frame: Screening Visit, Day 1, Day 7 and Follow-up Visit
description: 12-lead ECG
measure: Laboratory tests
time frame: Screening Visit, Day 8 of treatment period 4 or early withdrawal Visit and/or follow-up Visit
description: Clinical chemistry, hematology and urinalysis
measure: Adverse events
time frame: From the start of dosing with investigational product and until the follow-up visit.
description: adverse events
arm group label: FF/VI
arm group type: Experimental
description: 50/25 mcg, 100/25 mcg or 200/25 mcg
arm group label: Placebo
arm group type: Placebo Comparator
description: matching placebo
intervention type: Drug
intervention name: Fluticasone Furoate/Vilanterol
description: 50/25 or 100/25 or 200/25 mcg inhaled once daily for 7 days in each treatment period.
arm group label: FF/VI
intervention type: Drug
intervention name: Placebo
description: Placebo inhaled once daily for 7 days in each treatment period.
arm group label: Placebo
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: China
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: Fluticasone
mesh term: Xhance
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: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 