<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/NCT01725685</url>
  </required_header>
  <id_info>
    <org_study_id>116524</org_study_id>
    <nct_id>NCT01725685</nct_id>
  </id_info>
  <brief_title>To Investigate the Pharmacokinetics and Safety of Fluticasone Furoate (FF)/ Umeclidinium (UMEC) Combination Compared With FF and UMEC Monotherapies in Adult Healthy Volunteers Using a Dry Powder Inhaler (DPI)</brief_title>
  <official_title>A Randomized, Double Blind, Single-dose, Three-period, Crossover Study to Investigate Pharmacokinetic, Safety and Tolerability of Fluticasone Furoate With Umeclidinium When Administered in Combination and as Monotherapies in Adult Healthy Volunteer Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a randomized, double-blind, single-dose, three-period balanced crossover study&#xD;
      in adult healthy subjects. Each of the 18 subjects will be randomized to receive a treatment&#xD;
      sequence consisting of each of the three treatments (FF 400 microgram (mcg), UMEC 500 mcg and&#xD;
      FF 400 mcg/UMEC 500 mcg), in three consecutive periods, with a wash-out period of 7 to 10&#xD;
      days between the periods.&#xD;
&#xD;
      The study will include a Screening period (28 days prior to first dose), Treatment period (3&#xD;
      single dose periods separated by two 7 to 10 days washout periods) and Follow-up period (7 to&#xD;
      14 days post last dose).&#xD;
&#xD;
      The pharmacokinetic (PK) and safety assessments will be performed during the study at fixed&#xD;
      timepoints.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 8, 2012</start_date>
  <completion_date type="Actual">January 2, 2013</completion_date>
  <primary_completion_date type="Actual">January 2, 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>Maximum observed plasma concentration (Cmax) in plasma for FF and UMEC</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 minutes [mins], 15 mins, 30 mins, 45 mins, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The PK parameter Cmax will be calculated for FF/UMEC in combination and as monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC(0-t)), where t is time of last measurable concentration in plasma for FF and UMEC</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The PK parameter AUC(0-t) will be calculated for will be calculated for FF/UMEC in combination and as monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-inf)] in plasma for FF and UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The PK parameter AUC(0-inf) will be calculated for will be calculated for FF/UMEC in combination and as monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of maximum observed concentration (tmax) in plasma for FF and UMEC</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of last measurable concentration (tlast) in plasma for FF and UMEC</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma elimination half life (t½) in plasma for FF and UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination rate constant (Lambda z) in plasma for FF and UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent clearance (CL/F) in plasma for FF and UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution (V/F) in plasma for FF and UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative amount excreted drug in urine (Ae) for UMEC</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2(0-24 h)</time_frame>
    <description>The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of dose excreted (% Fe) in urine for UMEC</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2 (0-24 h)</time_frame>
    <description>The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine half life (urine t½) for UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2 (0-24 h)</time_frame>
    <description>The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal clearance (CLr) in urine for UMEC, if data permits</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 6-8 h, 8-12 h, 12-16 h) and Day 2(16-24 h)</time_frame>
    <description>The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve from time zero (pre-dose) to the time at which AUC is calculable for all subjects (AUC(0-t')), where t' is the time at which AUC is calculable for all the subjects</measure>
    <time_frame>Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)</time_frame>
    <description>The PK parameter AUC(0-t') will be calculated for will be calculated for FF/UMEC in combination and as monotherapies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Safety data assessed as number of adverse events (AE) in each treatment group</measure>
    <time_frame>Period 1 Day 1 dose to Follow up visit</time_frame>
    <description>Safety and tolerability will be assessed by recording of AEs for subjects receiving FF/UMEC in combination compared with FF and UMEC monotherapies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical laboratory measurements for each treatment group</measure>
    <time_frame>Period 1, 2 and 3: Baseline (Day -1) and Day 2</time_frame>
    <description>Safety and tolerability will be assessed by measuring the clinical laboratory parameters which include hematology, clinical chemistry, routine urinalysis and additional parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systolic and diastolic blood pressure for each treatment group</measure>
    <time_frame>Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit</time_frame>
    <description>Safety and tolerability will be assessed by measuring vital signs which include systolic and diastolic blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate for each treatment group</measure>
    <time_frame>Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit</time_frame>
    <description>Safety and tolerability will be assessed by measuring vital signs which include heart rate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-lead electrocardiogram (ECG) for each treatment group</measure>
    <time_frame>Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit</time_frame>
    <description>Safety and tolerability will be assessed by measuring ECG using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Treatment A - FF 400 microgram (mcg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be randomized to single dose of FF 400 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B - UMEC 500 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be randomized to single dose of UMEC 125 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C - FF/UMEC 400/500 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be randomized to single dose of FF/UMEC 100/125 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF 400 mcg</intervention_name>
    <description>FF will be available as 100 mcg strength administered as 4 inhalations from a DPI</description>
    <arm_group_label>Treatment A - FF 400 microgram (mcg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>UMEC 500 mcg</intervention_name>
    <description>UMEC will be available as 125 mcg strength administered as 4 inhalations from a DPI</description>
    <arm_group_label>Treatment B - UMEC 500 mcg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF/UMEC 400/500 mcg</intervention_name>
    <description>FF/UMEC will be available as 100/125 mcg strength administered as 4 inhalations from a DPI</description>
    <arm_group_label>Treatment C - FF/UMEC 400/500 mcg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#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.&#xD;
&#xD;
          -  A subject with a clinical abnormality or laboratory parameters outside the reference&#xD;
             range for the population being studied may be included only if the Investigator and&#xD;
             the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to&#xD;
             introduce additional risk factors and will not interfere with the study procedures.&#xD;
&#xD;
          -  Male or female between 18 and 65 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;
             is abstinent or agrees to use the contraception methods listed in Protocol for an&#xD;
             appropriate period of time (as determined by the product label or investigator) prior&#xD;
             to the start of dosing to sufficiently minimize the risk of pregnancy at that point.&#xD;
             Female subjects must agree to use contraception until the follow up visit (i.e. until&#xD;
             after the follow up visit is complete; Non-childbearing potential defined as&#xD;
             pre-menopausal females with a documented tubal ligation or hysterectomy; or&#xD;
             postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a&#xD;
             blood sample with simultaneous follicle stimulating hormone (FSH) &gt; 40 million&#xD;
             international units (MlU)/milliliter (ml) and estradiol &lt;40 picograms (pg)/ml (&lt;147&#xD;
             pmol/L) is confirmatory] Females on hormone replacement therapy (HRT) and whose&#xD;
             menopausal status is in doubt will be required to use the contraception methods listed&#xD;
             in Protocol if they wish to continue their HRT during the study. Otherwise, they must&#xD;
             discontinue HRT to allow confirmation of postmenopausal status prior to study&#xD;
             enrollment. For most forms of HRT, at least 2 to 4 weeks should elapse between the&#xD;
             cessation of therapy and the blood draw; this interval depends on the type and dosage&#xD;
             of HRT. Following confirmation of their post-menopausal status, they can resume use of&#xD;
             HRT during the study without use of a contraceptive method.&#xD;
&#xD;
          -  Women who are confirmed postmenopausal or permanently sterilized (e.g. tubal&#xD;
             occlusion, tubal ligation, hysterectomy, bilateral salpingectomy).&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use one of&#xD;
             the contraception methods listed in Protocol. This criterion must be followed from the&#xD;
             time of the first dose of study medication until the follow up visit.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin &lt;=1.5xupper limit&#xD;
             of normal (ULN) (isolated bilirubin &gt;1.5xULN is acceptable if bilirubin is&#xD;
             fractionated and direct bilirubin &lt;35%).&#xD;
&#xD;
          -  Average QT duration corrected for heart rate by Fridericia's formula (QTcF) &lt; 450&#xD;
             miliseconds (msec).&#xD;
&#xD;
          -  Body mass index (BMI) within the range 19 to 33 kilogram (kg)/meter square (m2)&#xD;
             (inclusive).&#xD;
&#xD;
          -  Subjects who are current non-smokers who have not used any tobacco products in the&#xD;
             6-month period preceding the screening visit and have a pack history of ≤10 pack&#xD;
             years.[number of pack years = (number of cigarettes per day /20) x number of years&#xD;
             smoked]&#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&#xD;
             abnormalities.&#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 mililitre [mL]) 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;
          -  Unable to refrain from the use of prescription or non-prescription drugs, including&#xD;
             vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or&#xD;
             14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is&#xD;
             longer) prior to the first dose of study medication, unless in the opinion of the&#xD;
             Investigator and GSK Medical Monitor the medication will not interfere with the study&#xD;
             procedures or compromise subject safety.&#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 or urine hCG test at screening or&#xD;
             prior to dosing.&#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;
          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.&#xD;
&#xD;
          -  History of respiratory disease (i.e. history of asthmatic symptoms) in the last 10&#xD;
             years.&#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 pummelos, exotic citrus fruits, grapefruit hybrids or fruit&#xD;
             juices from 7 days prior to the first dose of study medication.&#xD;
&#xD;
          -  Known or suspected sensitivity to the constituents of the DPI or a history of severe&#xD;
             milk protein allergy.&#xD;
&#xD;
          -  A supine mean heart rate outside the range 40 to 90 beats per minute (bpm) at&#xD;
             screening.&#xD;
&#xD;
          -  Diseases preventing use of anticholinergics: Diagnosis of narrow-angle glaucoma, or&#xD;
             bladder neck obstruction that in the opinion of the study investigator or GSK medical&#xD;
             monitor would pose a safety risk with use of an inhaled anticholinergic.&#xD;
&#xD;
          -  Other concurrent diseases/abnormalities: A subject must not have any clinically&#xD;
             significant, uncontrolled condition or disease state that, in the opinion of the&#xD;
             investigator, would put the safety of the patient at risk through study participation&#xD;
             if the condition/disease exacerbated during the study. The investigator is encouraged&#xD;
             to contact the study medical monitor if further clarification is required.&#xD;
&#xD;
          -  Affiliation with the investigators site&#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>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>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 14, 2012</study_first_posted>
  <last_update_submitted>June 7, 2017</last_update_submitted>
  <last_update_submitted_qc>June 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>healthy volunteers</keyword>
  <keyword>Umeclidinium</keyword>
  <keyword>tolerability</keyword>
  <keyword>Safety</keyword>
  <keyword>Fluticasone Furoate</keyword>
  <keyword>Pharmacokinetics</keyword>
  <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>116524</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>116524</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>116524</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>116524</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>116524</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>116524</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>116524</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/NCT01725685
org study id: 116524
nct id: NCT01725685
lead sponsor: 
collaborator: 
has dmc: No
This will be a randomized, double-blind, single-dose, three-period balanced crossover study
      in adult healthy subjects. Each of the 18 subjects will be randomized to receive a treatment
      sequence consisting of each of the three treatments (FF 400 microgram (mcg), UMEC 500 mcg and
      FF 400 mcg/UMEC 500 mcg), in three consecutive periods, with a wash-out period of 7 to 10
      days between the periods.

      The study will include a Screening period (28 days prior to first dose), Treatment period (3
      single dose periods separated by two 7 to 10 days washout periods) and Follow-up period (7 to
      14 days post last dose).

      The pharmacokinetic (PK) and safety assessments will be performed during the study at fixed
      timepoints.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Maximum observed plasma concentration (Cmax) in plasma for FF and UMEC
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 minutes [mins], 15 mins, 30 mins, 45 mins, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The PK parameter Cmax will be calculated for FF/UMEC in combination and as monotherapies
measure: Area under the concentration-time curve (AUC(0-t)), where t is time of last measurable concentration in plasma for FF and UMEC
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The PK parameter AUC(0-t) will be calculated for will be calculated for FF/UMEC in combination and as monotherapies
measure: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-inf)] in plasma for FF and UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The PK parameter AUC(0-inf) will be calculated for will be calculated for FF/UMEC in combination and as monotherapies
measure: Time of maximum observed concentration (tmax) in plasma for FF and UMEC
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies
measure: Time of last measurable concentration (tlast) in plasma for FF and UMEC
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies
measure: Plasma elimination half life (t½) in plasma for FF and UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies
measure: Elimination rate constant (Lambda z) in plasma for FF and UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies
measure: Apparent clearance (CL/F) in plasma for FF and UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies
measure: Apparent volume of distribution (V/F) in plasma for FF and UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The FF and UMEC PK parameter in plasma will be calculated to compare the PK of FF/UMEC in combination with FF and UMEC monotherapies
measure: Cumulative amount excreted drug in urine (Ae) for UMEC
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2(0-24 h)
description: The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy
measure: Percent of dose excreted (% Fe) in urine for UMEC
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2 (0-24 h)
description: The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy
measure: Urine half life (urine t½) for UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 0-8 h, 0-12 h, 0-16 h) and Day 2 (0-24 h)
description: The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy
measure: Renal clearance (CLr) in urine for UMEC, if data permits
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 0-6 h, 6-8 h, 8-12 h, 12-16 h) and Day 2(16-24 h)
description: The UMEC PK parameter in urine will be calculated to compare the PK of UMEC when co-administered with FF; with UMEC as a monotherapy
measure: Area under the concentration-time curve from time zero (pre-dose) to the time at which AUC is calculable for all subjects (AUC(0-t')), where t' is the time at which AUC is calculable for all the subjects
time frame: Period 1, 2 and 3: Day 1 (pre-dose, 5 mins, 15 mins, 30 mins, 45 mins, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h) and Day 2 (24 h)
description: The PK parameter AUC(0-t') will be calculated for will be calculated for FF/UMEC in combination and as monotherapies
measure: Clinical Safety data assessed as number of adverse events (AE) in each treatment group
time frame: Period 1 Day 1 dose to Follow up visit
description: Safety and tolerability will be assessed by recording of AEs for subjects receiving FF/UMEC in combination compared with FF and UMEC monotherapies.
measure: Clinical laboratory measurements for each treatment group
time frame: Period 1, 2 and 3: Baseline (Day -1) and Day 2
description: Safety and tolerability will be assessed by measuring the clinical laboratory parameters which include hematology, clinical chemistry, routine urinalysis and additional parameters.
measure: Systolic and diastolic blood pressure for each treatment group
time frame: Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit
description: Safety and tolerability will be assessed by measuring vital signs which include systolic and diastolic blood pressure.
measure: Heart rate for each treatment group
time frame: Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit
description: Safety and tolerability will be assessed by measuring vital signs which include heart rate.
measure: 12-lead electrocardiogram (ECG) for each treatment group
time frame: Baseline (Day 1 pre-dose) and Day 2 of each treatment period; and Follow-up Visit
description: Safety and tolerability will be assessed by measuring ECG using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals.
arm group label: Treatment A - FF 400 microgram (mcg)
arm group type: Experimental
description: Subjects will be randomized to single dose of FF 400 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.
arm group label: Treatment B - UMEC 500 mcg
arm group type: Experimental
description: Subjects will be randomized to single dose of UMEC 125 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.
arm group label: Treatment C - FF/UMEC 400/500 mcg
arm group type: Experimental
description: Subjects will be randomized to single dose of FF/UMEC 100/125 mcg in either of the three treatment period, which is separated by a wash-out period of 7 to 10 days.
intervention type: Drug
intervention name: FF 400 mcg
description: FF will be available as 100 mcg strength administered as 4 inhalations from a DPI
arm group label: Treatment A - FF 400 microgram (mcg)
intervention type: Drug
intervention name: UMEC 500 mcg
description: UMEC will be available as 125 mcg strength administered as 4 inhalations from a DPI
arm group label: Treatment B - UMEC 500 mcg
intervention type: Drug
intervention name: FF/UMEC 400/500 mcg
description: FF/UMEC will be available as 100/125 mcg strength administered as 4 inhalations from a DPI
arm group label: Treatment C - FF/UMEC 400/500 mcg
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: 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
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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