A Dose-ranging Study of Fluticasone Furoate (FF)

A Dose-ranging Study of Fluticasone Furoate (FF) Inhalation Powder in Children Aged 5-11 Years With Asthma

This is a Phase IIb, multi-centre, stratified, randomised, double-blind, double-dummy, parallel-group, placebo and active controlled study in children aged 5-11 years with persistent uncontrolled asthma. Subjects meeting all of the inclusion criteria and none of the exclusion criteria at the screening visit (Visit 1) will enter a four week run-in period during which time they will continue their current medications. Visit 2 will occur two weeks into the run-in period to allow a review of compliance with daily diary and run-in medication. At Visit 3 (end of run-in/randomization visit), subjects meeting the eligibility criteria who remain uncontrolled despite baseline therapy will be stratified based on pre screening inhaled corticosteroid (ICS) use. Once stratified, subjects will be randomised to the treatment phase of the study where they will receive one of five treatments for 12 weeks. Approx 1200 subjects ages 5 to 11 will be screened to achieve 575 randomized for a total of 115 randomized/evaluable subjects per treatment arm. Subjects will attend on-treatment visits at 2, 4, 8 and 12 weeks (Visits 4, 5, 6 and 7 respectively). A follow-up contact will be performed one week after completing study medication. All subjects must attempt spirometry measurements at Visits 1 and 3. For all subjects, a timed 24-hour urine collection for urinary cortisol and creatinine excretion will be performed prior to randomization at Visit 2 and within 7 days prior to Visit 7. All subjects must perform PEF daily between visits 1 and 7. The primary endpoint will be change from baseline in pre-dose (i.e. dosing trough) PM PEF from patient hand held electronic daily diary at Endpoint (Endpoint is defined as the mean over the last 7 days of treatment). Safety assessments include adverse events, oropharyngeal examinations, clinical chemistry, urinary cortisol, and vital signs.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: Fluticasone Furoate; Drug: Fluticasone Propionate

• Study Type: Interventional
• Enrollment (Actual): 597
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • GSK Investigational Site
  • Plovdiv, Bulgaria, 4003
    • GSK Investigational Site
  • Ruse, Bulgaria, 7000
    • GSK Investigational Site
  • Sofia, Bulgaria
    • GSK Investigational Site
• Georgia
  • Tbilisi, Georgia, 0159
    • GSK Investigational Site
  • Tbilisi, Georgia, 0160
    • GSK Investigational Site
  • Tbilisi, Georgia, 0186
    • GSK Investigational Site
  • Tbilisi, Georgia, 0119
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10785
    • GSK Investigational Site
  • Hamburg, Germany, 22415
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Mannheim, Baden-Wuerttemberg, Germany, 68163
      • GSK Investigational Site
  • Bayern
    • Berchtesgaden, Bayern, Germany, 83471
      • GSK Investigational Site
    • Rosenheim, Bayern, Germany, 83026
      • GSK Investigational Site
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60596
      • GSK Investigational Site
    • Neu isenburg, Hessen, Germany, 63263
      • GSK Investigational Site
    • Niedernhausen, Hessen, Germany, 65527
      • GSK Investigational Site
  • Niedersachsen
    • Goettingen, Niedersachsen, Germany, 37073
      • GSK Investigational Site
    • Wolfenbuettel, Niedersachsen, Germany, 38302
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • GSK Investigational Site
    • Hamm, Nordrhein-Westfalen, Germany, 59063
      • GSK Investigational Site
    • Kleve-Materborn, Nordrhein-Westfalen, Germany, 47533
      • GSK Investigational Site
    • Telgte, Nordrhein-Westfalen, Germany, 48291
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
  • Schleswig-Holstein
    • Geesthacht, Schleswig-Holstein, Germany, 21502
      • GSK Investigational Site
  • Thueringen
    • Neuhaus am Rennweg, Thueringen, Germany, 98724
      • GSK Investigational Site
• Japan
  • Chiba, Japan, 260-0001
    • GSK Investigational Site
  • Fukuoka, Japan, 811-1394
    • GSK Investigational Site
  • Hiroshima, Japan, 720-8520
    • GSK Investigational Site
  • Hokkaido, Japan, 006-0831
    • GSK Investigational Site
  • Hokkaido, Japan, 064-0821
    • GSK Investigational Site
  • Hyogo, Japan, 653-0021
    • GSK Investigational Site
  • Kagawa, Japan, 762-0031
    • GSK Investigational Site
  • Mie, Japan, 514-0125
    • GSK Investigational Site
  • Osaka, Japan, 583-8588
    • GSK Investigational Site
  • Tokyo, Japan, 154-0017
    • GSK Investigational Site
  • Tokyo, Japan, 157-0066
    • GSK Investigational Site
  • Tokyo, Japan, 158-0097
    • GSK Investigational Site
  • Wakayama, Japan, 646-8558
    • GSK Investigational Site
• Latvia
  • Daugavpils, Latvia, LV5403
    • GSK Investigational Site
  • Rezekne, Latvia, LV-4601
    • GSK Investigational Site
  • Riga, Latvia, LV 1003
    • GSK Investigational Site
  • Riga, Latvia, LV 1004
    • GSK Investigational Site
  • Riga, Latvia, LV1011
    • GSK Investigational Site
• Mexico
  • Ciudad de México, Mexico, 06720
    • GSK Investigational Site
  • Mexico, Mexico, 04530
    • GSK Investigational Site
  • Mexico City, Mexico, 07760
    • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • GSK Investigational Site
    • Zapopan, Jalisco, Mexico, 45040
      • GSK Investigational Site
  • Michoacán
    • Morelia, Michoacán, Mexico, 58070
      • GSK Investigational Site
  • Tabasco
    • Villahermosa, Tabasco, Mexico, 86100
      • GSK Investigational Site
• Peru
  • Lima, Peru, Lima 11
    • GSK Investigational Site
  • Lima, Peru, Lima 27
    • GSK Investigational Site
  • Lima, Peru, Lima 29
    • GSK Investigational Site
  • Lima
    • Lima 18, Lima, Peru
      • GSK Investigational Site
    • Lima 27, Lima, Peru, Lima 27
      • GSK Investigational Site
    • San Borja, Lima, Peru, Lima 41
      • GSK Investigational Site
    • San Miguel, Lima, Peru, Lima 32
      • GSK Investigational Site
• Philippines
  • Manila, Philippines, 1000
    • GSK Investigational Site
  • Manila, Philippines, 1003
    • GSK Investigational Site
  • Quezon City, Philippines, 1113
    • GSK Investigational Site
• Poland
  • Bialystok, Poland, 15-430
    • GSK Investigational Site
  • Bialystok, Poland, 15-183
    • GSK Investigational Site
  • Bydgoszcz, Poland, 85-046
    • GSK Investigational Site
  • Debica, Poland, 39-200
    • GSK Investigational Site
  • Kielce, Poland, 25-017
    • GSK Investigational Site
  • Lodz, Poland, 93-513
    • GSK Investigational Site
  • Lublin, Poland, 20-093
    • GSK Investigational Site
  • Lublin, Poland, 20-552
    • GSK Investigational Site
  • Lublin, Poland, 20-089
    • GSK Investigational Site
  • Poznan, Poland, 60-693
    • GSK Investigational Site
  • Tarnow, Poland, 33-100
    • GSK Investigational Site
• Puerto Rico
  • Hato Rey, Puerto Rico, 00917
    • GSK Investigational Site
• Russian Federation
  • Blagoveshchensk, Russian Federation, 675000
    • GSK Investigational Site
  • Moscow, Russian Federation, 119991
    • GSK Investigational Site
  • Murmansk, Russian Federation, 183031
    • GSK Investigational Site
  • Novokuznetsk, Russian Federation, 654063
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630091
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 194356
    • GSK Investigational Site
  • Voronezh, Russian Federation, 394036
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150003
    • GSK Investigational Site
• South Africa
  • CapeTown, South Africa, 7764
    • GSK Investigational Site
  • Middelburg, South Africa, 1501
    • GSK Investigational Site
  • Western Province
    • Panorama, Western Province, South Africa, 7500
      • GSK Investigational Site
• Sweden
  • Göteborg, Sweden, SE-416 85
    • GSK Investigational Site
  • Kungsbacka, Sweden, SE-434 30
    • GSK Investigational Site
  • Stockholm, Sweden, SE-118 83
    • GSK Investigational Site
  • Stockholm, Sweden, SE171 76
    • GSK Investigational Site
  • Uppsala, Sweden, SE-752 26
    • GSK Investigational Site
  • Visby, Sweden, SE-621 84
    • GSK Investigational Site
  • Örebro, Sweden, SE-701 85
    • GSK Investigational Site
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • GSK Investigational Site
  • Ivano-Frankivsk, Ukraine, 76018
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61093
    • GSK Investigational Site
  • Kherson, Ukraine, 73000
    • GSK Investigational Site
  • Kyiv, Ukraine, 03680
    • GSK Investigational Site
  • Kyiv, Ukraine, 04050
    • GSK Investigational Site
  • Luhansk, Ukraine, 91000
    • GSK Investigational Site
  • Simferopol, Ukraine, 95034
    • GSK Investigational Site
  • Vinnytsia, Ukraine, 21021
    • GSK Investigational Site
  • Yevpatoriia, Ukraine, 97408
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69063
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69076
    • GSK Investigational Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • GSK Investigational Site
  • California
    • Costa Mesa, California, United States, 92626
      • GSK Investigational Site
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
    • Long Beach, California, United States, 90808
      • GSK Investigational Site
    • Newport Beach, California, United States, 92663
      • GSK Investigational Site
    • Orange, California, United States, 92868
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • GSK Investigational Site
    • Cocoa, Florida, United States, 32927
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • GSK Investigational Site
  • Idaho
    • Eagle, Idaho, United States, 83616
      • GSK Investigational Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • GSK Investigational Site
    • Shiloh, Illinois, United States, 62269
      • GSK Investigational Site
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • GSK Investigational Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • GSK Investigational Site
  • Michigan
    • Stevensville, Michigan, United States, 49127
      • GSK Investigational Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • GSK Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65203
      • GSK Investigational Site
    • Rolla, Missouri, United States, 65401
      • GSK Investigational Site
  • New York
    • Corning, New York, United States, 14830
      • GSK Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
    • Portland, Oregon, United States, 97202
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • GSK Investigational Site
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78750
      • GSK Investigational Site
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site
    • El Paso, Texas, United States, 79925
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78258
      • GSK Investigational Site
    • Waco, Texas, United States, 76712
      • GSK Investigational Site
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent from at least one parent/ legal guardian to take part in the study.:
• Diagnosis of asthma
• pre-bronchodilator PEF between ≥50% to ≤90% of their best post-bronchodilator value
• Receiving therapy of short acting beta-agonist (SABA) alone, LTM, or ICS (total daily dose <FP 200mcg or equivalent)Exclusion :

Exclusion Criteria:

• history of life-threatening asthma
• history of asthma exacerbation for asthma within 6 months prior to screening.
• Culture-documented or suspected bacterial or viral infection
• significant abnormality or medical condition
• Present use of any tobacco products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Fluticasone Furoate 100mcg inhalation powder once daily in the evening ICS powder	Drug: Fluticasone Furoate; current asthma medicine
Active Comparator: Arm 2; Fluticasone Furoate 50mcg inhalation powder once daily in the evening ICS powder	Drug: Fluticasone Furoate; current asthma medicine
Active Comparator: Arm 3; Fluticasone Furoate 25mcg inhalation powder once daily in the evening ics powder	Drug: Fluticasone Furoate; current asthma medicine
Active Comparator: Arm 4; Fluticasone Propionate 100mcg inhalation powder twice daily ICS powder	Drug: Fluticasone Propionate; Fluticasone propionate
Placebo Comparator: Arm 5; Placebo inhalation powder once daily in the evening Placebo powder	Drug: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Pre-dose Morning (AM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 12-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three measurements was recorded. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. The Baseline PEF value is defined as the average of the last 7 days of the Run-in Period. Statistical analysis was performed using an analysis of covariance (ANCOVA) model with covariates of Baseline AM PEF, actual pre-screening inhaled corticosteroid (ICS) use, region, sex, age, and treatment. Particpants analyzed included those who have PEF data for at least 2 non-missing days in the Baseline week prior to randomisation and at least 2 non-missing days after randomisation.	Baseline; Week 1 up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Evening Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-week Treatment Period in Children Who Could Perform the Maneuver	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as a pre-dose FEV1 measurement taken at a clinic visit while still on treatment. Change from Baseline was calculated as the Week 12 trough FEV1 value minus the Baseline value. The Baseline FEV1 value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline trough FEV1, region, actual pre-screening ICS use, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing measurements. Only those participants available at the specified time points were analyzed.	Baseline, Week 12
Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period	The number of inhalations of rescue albuterol/salbutamol aerosol (medication used to relieve symptoms immediately) used during the day and night) was recorded by the participants in a daily diary. A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. The Baseline rescue-free value was defined as the percentage of rescue-free 24-hr periods from the last 7 days of the Run-in Period. Change from Baseline was calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, actual pre-screening ICS use, age, and treatment.	Baseline; Week 1 up to Week 12
Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 12-week Treatment Period (at Week 12) minus the Baseline value. The Baseline PEF value is defined as the average of the last 7 days of the Run-in Period. Statistical analysis was performed using ANCOVA model with covariates of Baseline, actual pre-screening ICS use, region, sex, age, and treatment. Particpants analyzed included those who have PEF data for at least 2 non-missing days in the Baseline week prior to randomisation and at least 2 non-missing days after randomisation.	Baseline; Week 1 up to Week 12
Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12)	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline in PM PEF was calculated as the value over the last 7 days of the Treatment Period minus the Baseline value. The Baseline PEF value is defined as the average of the last 7 days of the Run-in Period. Statistical analysis was performed using ANCOVA model with covariates of Baseline, actual pre-screening ICS use, region, sex, age, and treatment. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurements.	Baseline; Week 12
Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12)	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline in AM PEF was calculated as the value over the last 7 days of the Treatment Period minus the Baseline value. The Baseline PEF value is defined as the average of the last 7 days of the Run-in Period. Statistical analysis was performed using ANCOVA model with covariates of Baseline, pre-screening ICS use, region, sex, age, and treatment. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurements.	Baseline; Week 12
Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period	Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the PEF measurement. A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline symptom-free value is defined as the percentage of symptom free 24-hr periods in the last 7 days of the run-in period. Change from Baseline was calculated as the averaged value during the 12-week Treatment Period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, actual pre-screening ICS use, age, and treatment group.	Baseline; Week 1 up to Week 12
Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period	The number of participants whose primary reason for withdrawal from the study was due to lack of efficacy is presented together with p-values for the treatment comparisons.	Up to Week 12

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Oliver AJ, Covar RA, Goldfrad CH, Klein RM, Pedersen SE, Sorkness CA, Tomkins SA, Villaran C, Grigg J. Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma. J Pediatr. 2016 Nov;178:246-253.e2. doi: 10.1016/j.jpeds.2016.08.010. Epub 2016 Sep 9.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2012
• Primary Completion (Actual): September 24, 2014
• Study Completion (Actual): September 24, 2014

Study Registration Dates

• First Submitted: March 15, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 26, 2012

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 106855

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan 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 Data/Documents

1. Individual Participant Data Set
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 106855
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register