A Dose-ranging Study of Fluticasone Furoate (FF)

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01563029
• Other study ID #: 106855
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2012
• Last updated: June 25, 2015
• Start date: March 2012
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 597
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 11 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone Furoate
current asthma medicine
• Fluticasone Propionate
Fluticasone propionate
• Placebo
placebo

Locations

Country	Name	City	State
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Ruse
Bulgaria	GSK Investigational Site	Sofia
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Germany	GSK Investigational Site	Berchtesgaden	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamm	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kleve-Materborn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Neu isenburg	Hessen
Germany	GSK Investigational Site	Neuhaus am Rennweg	Thueringen
Germany	GSK Investigational Site	Niedernhausen	Hessen
Germany	GSK Investigational Site	Rosenheim	Bayern
Germany	GSK Investigational Site	Telgte	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wolfenbuettel	Niedersachsen
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Wakayama
Latvia	GSK Investigational Site	Daugavpils
Latvia	GSK Investigational Site	Rezekne
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Mexico	GSK Investigational Site	Ciudad de México
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Morelia	Michoacán
Mexico	GSK Investigational Site	Villahermosa	Tabasco
Mexico	GSK Investigational Site	Zapopan	Jalisco
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima 18	Lima
Peru	GSK Investigational Site	Lima 27	Lima
Peru	GSK Investigational Site	San Borja	Lima
Peru	GSK Investigational Site	San Miguel	Lima
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Quezon City
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Tarnow
Puerto Rico	GSK Investigational Site	Hato Rey
Russian Federation	GSK Investigational Site	Blagoveshchensk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Murmansk
Russian Federation	GSK Investigational Site	Novokuznetsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Yaroslavl
South Africa	GSK Investigational Site	CapeTown
South Africa	GSK Investigational Site	Middelburg
South Africa	GSK Investigational Site	Panorama	Western Province
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Kungsbacka
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Uppsala
Sweden	GSK Investigational Site	Visby
Ukraine	GSK Investigational Site	Chernivtsi
Ukraine	GSK Investigational Site	Ivano-Frankivsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kherson
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Luhansk
Ukraine	GSK Investigational Site	Simferopol
Ukraine	GSK Investigational Site	Vinnytsia
Ukraine	GSK Investigational Site	Yevpatoriia
Ukraine	GSK Investigational Site	Zaporizhia
Ukraine	GSK Investigational Site	Zaporizhia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cocoa	Florida
United States	GSK Investigational Site	Columbia	Missouri
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Corning	New York
United States	GSK Investigational Site	Costa Mesa	California
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Eagle	Idaho
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Normal	Illinois
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Owensboro	Kentucky
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Plymouth	Minnesota
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rolla	Missouri
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Shiloh	Illinois
United States	GSK Investigational Site	South Burlington	Vermont
United States	GSK Investigational Site	Stevensville	Michigan
United States	GSK Investigational Site	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Bulgaria,  Georgia,  Germany,  Japan,  Latvia,  Mexico,  Peru,  Philippines,  Poland,  Puerto Rico,  Russian Federation,  South Africa,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No