<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/NCT01669070</url>
  </required_header>
  <id_info>
    <org_study_id>115441</org_study_id>
    <nct_id>NCT01669070</nct_id>
  </id_info>
  <brief_title>A Four-way Crossover, Single and Repeat Dose Study to Determine the Dose Proportionality and Absolute Bioavailability of Fluticasone Furoate Inhalation Powder Administered by Novel Dry Powder Inhaler (NDPI)</brief_title>
  <official_title>An Open Label, Part-randomised, Four-way Crossover, Single and Repeat Dose Study to Determine the Dose Proportionality and Absolute Bioavailability of Fluticasone Furoate (FF) When Administered as FF Inhalation Powder From the Novel Dry Powder Inhaler in Healthy 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>
      The purpose of this study is to demonstrate dose proportionality of the FF (50 microgram&#xD;
      (mcg), 100 mcg or 200 mcg), when administered as a single and repeat dose from the NDPI&#xD;
      containing FF formulated with lactose. In addition, the aim of this study is to determine the&#xD;
      absolute bioavailability of the FF single strip product using the high strength product&#xD;
      administered as a single dose with multiple inhalations and using 250 mcg intravenous (IV)&#xD;
      FF.&#xD;
&#xD;
      This is a, part-randomized, open-label, 4 way crossover study (4 periods) in healthy adult&#xD;
      subjects. During each period, subjects will receive FF in the morning and serial&#xD;
      pharmacokinetic (PK) sampling (for up to 10 days for the inhaled treatment and up to 3 days&#xD;
      for the IV treatment) and safety assessments will be performed. Each period will be separated&#xD;
      by a washout period of at least 7 days and a follow-up telephone call will occur 7 -14 days&#xD;
      after the last dose of study drug. The total duration of the study will be approximately&#xD;
      13-14 weeks for each subject.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 15, 2012</start_date>
  <completion_date type="Actual">November 16, 2012</completion_date>
  <primary_completion_date type="Actual">November 16, 2012</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>FF pharmacokinetics; parameters: (AUC(0-infinity)) , (AUC(0-24)) and (Cmax)</measure>
    <time_frame>54 days</time_frame>
    <description>FF pharmacokinetics; 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 zero (pre-dose) to 24 h (AUC (0-24)) and maximum observed concentration (Cmax). Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma FF PK parameters: t1/2, tmax, MRT for all treatments</measure>
    <time_frame>54 days</time_frame>
    <description>Following plasma FF PK parameters will be evaluated: terminal phase half life (t1/2), time of occurrence of Cmax (tmax), mean residence time (MRT) for all treatments Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma FF PK parameters: V and CL for IV treatment</measure>
    <time_frame>3 days (Study Day 52 to Study Day 54)</time_frame>
    <description>Following plasma FF PK parameters will be evaluated: volume of distribution (V) and plasma clearance (CL) for intravenous administration Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean absorption time (MAT) for inhaled treatments</measure>
    <time_frame>44 days</time_frame>
    <description>Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of FF</measure>
    <time_frame>68 days</time_frame>
    <description>To assess the safety and tolerability of FF administered as single and repeat dose adverse events will be studied.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>FF 50 mcg powder inhalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive a single dose of 300 mcg FF (6 inhalations of 50 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 50 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FF 100 mcg powder inhalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive a single dose of 600 mcg FF (6 inhalations of 100 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 100 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FF 200 mcg powder inhalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive a single dose of 1200 mcg FF (6 inhalations of 200 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 200 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FF 250 mcg IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive a single dose of 250 mcg FF, administered as an IV infusion over 20 minutes on Day 1 of the respective period per randomization sequence.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF, 50 mcg</intervention_name>
    <description>Novel dry powder inhaler</description>
    <arm_group_label>FF 50 mcg powder inhalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF, 100 mcg</intervention_name>
    <description>Novel dry powder inhaler</description>
    <arm_group_label>FF 100 mcg powder inhalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF, 200 mcg</intervention_name>
    <description>Novel dry powder inhaler</description>
    <arm_group_label>FF 200 mcg powder inhalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF, 250 mcg</intervention_name>
    <description>Intravenous</description>
    <arm_group_label>FF 250 mcg IV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male or female subjects between 18 and 65 years of age and body mass index&#xD;
             (BMI) within the range 18.5 to 29.0 kilogram/meter squared.&#xD;
&#xD;
          -  Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and bilirubin &lt; or&#xD;
             =1.5x upper limit of normal (ULN).&#xD;
&#xD;
          -  Female subjects of child bearing potential are eligible to enter if they are not&#xD;
             pregnant and willing to use protocol-specified methods of contraception to prevent&#xD;
             pregnancy during the study.&#xD;
&#xD;
          -  Average QT duration corrected for heart rate by Fridericia's formula (QTcF) &lt;450&#xD;
             millisecond.&#xD;
&#xD;
          -  Forced Expiratory Volume in 1 Second (FEV1) &gt; or = 85% predicted at screening.&#xD;
&#xD;
          -  Current non-smokers&#xD;
&#xD;
          -  Able to satisfactorily use the NDPI.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects must not have a systolic blood pressure above 145 milimeter(mm) of&#xD;
             mercury(Hg) or a diastolic pressure above 85 mmHg at the screening visit.&#xD;
&#xD;
          -  History of breathing problems in adult life confirmed by normal lung function&#xD;
             parameters (≥85% predicted).&#xD;
&#xD;
          -  Donation of more than 500 mL blood within a 56 day period.&#xD;
&#xD;
          -  Subjects who have suffered a lower respiratory tract infection within 4 weeks of the&#xD;
             screening visit.&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary&#xD;
             abnormalities.&#xD;
&#xD;
          -  The subject treated for or diagnosed with depression within six months of screening or&#xD;
             has a history of significant psychiatric illness.&#xD;
&#xD;
          -  The subject has a positive: drug/alcohol, Hepatitis, HIV screen.&#xD;
&#xD;
          -  Abuse of alcohol.&#xD;
&#xD;
          -  Subject having positive cotinine and urine alcohol test.&#xD;
&#xD;
          -  Participated in &gt;3 clinical trials in the previous 10 months (if male), or &gt;2 clinical&#xD;
             trials in the previous 10 months (if female), or the subject has participated in a&#xD;
             study (including follow up) within 60 days prior to the first dosing day in the&#xD;
             current study.&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Taken systemic, oral or depot corticosteroids less than 12 weeks or inhaled,&#xD;
             intranasal or topical steroids less than 4 weeks before the screening visit.&#xD;
&#xD;
          -  Use of prescription or non-prescription drugs.&#xD;
&#xD;
          -  History of severe milk protein allergy, sensitivity to any of the study medications,&#xD;
             including immediate or delayed hypersensitivity to any intranasal, inhaled or systemic&#xD;
             corticosteroid therapy.&#xD;
&#xD;
          -  Pregnant or lactating females.&#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>65 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>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</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 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>
  <keyword>bioavailability</keyword>
  <keyword>Fluticasone Furoate</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>dose proportionality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
  </condition_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>115441</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>115441</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>115441</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>115441</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>115441</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>115441</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>115441</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_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/NCT01669070
org study id: 115441
nct id: NCT01669070
lead sponsor: 
has dmc: No
The purpose of this study is to demonstrate dose proportionality of the FF (50 microgram
      (mcg), 100 mcg or 200 mcg), when administered as a single and repeat dose from the NDPI
      containing FF formulated with lactose. In addition, the aim of this study is to determine the
      absolute bioavailability of the FF single strip product using the high strength product
      administered as a single dose with multiple inhalations and using 250 mcg intravenous (IV)
      FF.

      This is a, part-randomized, open-label, 4 way crossover study (4 periods) in healthy adult
      subjects. During each period, subjects will receive FF in the morning and serial
      pharmacokinetic (PK) sampling (for up to 10 days for the inhaled treatment and up to 3 days
      for the IV treatment) and safety assessments will be performed. Each period will be separated
      by a washout period of at least 7 days and a follow-up telephone call will occur 7 -14 days
      after the last dose of study drug. The total duration of the study will be approximately
      13-14 weeks for each subject.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: FF pharmacokinetics; parameters: (AUC(0-infinity)) , (AUC(0-24)) and (Cmax)
time frame: 54 days
description: FF pharmacokinetics; 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 zero (pre-dose) to 24 h (AUC (0-24)) and maximum observed concentration (Cmax). Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.
measure: Plasma FF PK parameters: t1/2, tmax, MRT for all treatments
time frame: 54 days
description: Following plasma FF PK parameters will be evaluated: terminal phase half life (t1/2), time of occurrence of Cmax (tmax), mean residence time (MRT) for all treatments Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.
measure: Plasma FF PK parameters: V and CL for IV treatment
time frame: 3 days (Study Day 52 to Study Day 54)
description: Following plasma FF PK parameters will be evaluated: volume of distribution (V) and plasma clearance (CL) for intravenous administration Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.
measure: Mean absorption time (MAT) for inhaled treatments
time frame: 44 days
description: Blood samples for PK analysis of FF will be collected and analysis will be performed. Concentrations of FF will be determined in plasma samples using the currently approved analytical methodology.
measure: Safety of FF
time frame: 68 days
description: To assess the safety and tolerability of FF administered as single and repeat dose adverse events will be studied.
arm group label: FF 50 mcg powder inhalation
arm group type: Experimental
description: Each subject will receive a single dose of 300 mcg FF (6 inhalations of 50 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 50 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI.
arm group label: FF 100 mcg powder inhalation
arm group type: Experimental
description: Each subject will receive a single dose of 600 mcg FF (6 inhalations of 100 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 100 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI.
arm group label: FF 200 mcg powder inhalation
arm group type: Experimental
description: Each subject will receive a single dose of 1200 mcg FF (6 inhalations of 200 mcg FF) on Day 1 of the respective period per randomization sequence, followed by 200 mcg FF once daily for 7 days, on Days 3-9 inclusive, administered from the NDPI.
arm group label: FF 250 mcg IV
arm group type: Experimental
description: Each subject will receive a single dose of 250 mcg FF, administered as an IV infusion over 20 minutes on Day 1 of the respective period per randomization sequence.
intervention type: Drug
intervention name: FF, 50 mcg
description: Novel dry powder inhaler
arm group label: FF 50 mcg powder inhalation
intervention type: Drug
intervention name: FF, 100 mcg
description: Novel dry powder inhaler
arm group label: FF 100 mcg powder inhalation
intervention type: Drug
intervention name: FF, 200 mcg
description: Novel dry powder inhaler
arm group label: FF 200 mcg powder inhalation
intervention type: Drug
intervention name: FF, 250 mcg
description: Intravenous
arm group label: FF 250 mcg IV
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: Netherlands
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: Respiratory Aspiration
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: 