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A randomised, double-blind, placebo-controlled (with rescue medication), multi-centre study to evaluate the efficacy and safety of inhaled fluticasone furoate in the treatment of persistent asthma in adults and adolescents not currently receiving inhaled corticosteroids
This will be a multi-centre, randomised, placebo controlled (with rescue medication), double-blind, parallel group study. Subjects meeting all the inclusion criteria and none of the exclusion criteria during Visit 1 (Screening Visit) will enter a two week Run-in Period. Subjects failing screening will not be eligible for re-screening. During the run-in and double-blind treatment periods subjects will maintain an electronic daily diary to record morning and evening peak expiratory flow (PEF), asthma symptom score and rescue albuterol/salbutamol use. At Visit 2 (end of run-in/Randomisation Visit), subjects meeting the eligibility criteria will be randomised to either inhaled Fluticasone Furoate 50 mcg or inhaled placebo. In addition all subjects will be supplied with albuterol/salbutamol inhalation aerosol to use as required to treat symptoms. Subjects will attend 4 on-treatment visits at Visits 3, 4, 5, and 6 (Weeks 2, 4, 8 and 12 respectively). Subjects will receive treatment for 84 days (12 weeks). A follow-up contact will be performed 1-week after completing study medication (Visit 7). Subjects will participate in the study for up to a maximum of 15 weeks (including screening, treatment and follow-up contact).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluticasone furoate 50mcg | Experimental | Inhalation powder delivered by Novel Dry Powder Inhaler |
|
| Placebo | Placebo Comparator | Inhalation powder delivered by Novel Dry Powder Inhaler |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluticasone furoate 50mcg | Drug | Inhalation powder delivered by Novel Dry Powder Inhaler |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Clinic Visit Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-week Treatment Period | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Evening clinic visit FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the Week 12 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were measured electronically by spirometry in the evening at the Baseline through Week 12 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing, pre-dose, post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing value. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Over the 12-week Treatment Period | The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. A 24-hour period was considered as missing if both day time and night time values were missing or if one of the day time or night time values were missing and the other value indicated no use of rescue medication. The Baseline value is the average of the values over the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Long Beach | California | 90808 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27881132 | Derived | O'Byrne PM, Jacques L, Goldfrad C, Kwon N, Perrio M, Yates LJ, Busse WW. Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma. Respir Res. 2016 Nov 24;17(1):157. doi: 10.1186/s12931-016-0473-x. | |
| 25108545 | Derived | O'Byrne PM, Woodcock A, Bleecker ER, Bateman ED, Lotvall J, Forth R, Medley H, Jacques L, Busse WW. Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial. Respir Res. 2014 Aug 11;15(1):88. doi: 10.1186/s12931-014-0088-z. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 115283 | Statistical Analysis Plan | View IPD |
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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Participants meeting eligibility criteria at the Screening visit entered a 2-week Run-in Period for Baseline safety evaluations and to obtain measures of asthma status. Participants were then randomized to a 12-week Treatment Period. A total of 449 participants were screened; 248 were randomized, and 242 received >=1 dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. |
| FG001 | FF 50 µg OD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | Inhalation powder delivered by Novel Dry Powder Inhaler |
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| From Baseline up to Week 12 |
| Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period | PEF is a measure of lung function and 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 and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 12 |
| Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period | PEF is a measure of lung function and 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 and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 12 |
| Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over 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 peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. A 24-hour period was considered as missing if both the day time and night time data were missing or if one was symptom-free but the other was missing. The Baseline value was the average of the values of the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 12 |
| Number of Participants Who Withdrew Due to a Lack of Efficacy During the 12-week Treatment Period | The reason for withdrawal was lack of efficacy if a participant was withdrawn due to: clinic FEV1 falling below the FEV1 stability limit; participant experiencing at least 4 days of AM or PM PEF falling below the PEF stability limit and/or at least 3 days of >=12 inhalations/day of albuterol/salbutamol usage during the 7 days immediately preceding any contact; or the occurrence of an asthma exacerbation, defined as the deterioration of asthma requiring the use of systemic (oral, parenteral, or depot) corticosteroids for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. The FEV1 stability limit was calculated as the best pre-salbutamol/albuterol FEV1 at Visit 2 * 80%. The PEF stability limit was calculated as the mean AM PEF from the available 7 consecutive days preceding Visit 2 * 80%. | From the first dose of the study medication until Week 12/Early Withdrawal |
| Los Angeles |
| California |
| 90025 |
| United States |
| GSK Investigational Site | Newport Beach | California | 92663 | United States |
| GSK Investigational Site | Albany | Georgia | 31707 | United States |
| GSK Investigational Site | Columbia | Missouri | 65203 | United States |
| GSK Investigational Site | Oklahoma City | Oklahoma | 73103 | United States |
| GSK Investigational Site | Orangeburg | South Carolina | 29118 | United States |
| GSK Investigational Site | Spartanburg | South Carolina | 29303 | United States |
| GSK Investigational Site | Corsicana | Texas | 75110 | United States |
| GSK Investigational Site | Waco | Texas | 76712 | United States |
| GSK Investigational Site | Zapopan | Jalisco | 45040 | Mexico |
| GSK Investigational Site | Morelia | Michoacán | 58070 | Mexico |
| GSK Investigational Site | Villahermosa | Tabasco | 86100 | Mexico |
| GSK Investigational Site | Lima | Lima Province | Lima 1 | Peru |
| GSK Investigational Site | Lima | Lima Province | Lima 27 | Peru |
| GSK Investigational Site | Lima | Lima Province | Peru |
| GSK Investigational Site | San Borja | Lima region | Lima 41 | Peru |
| GSK Investigational Site | San Miguel | Lima region | Lima 32 | Peru |
| GSK Investigational Site | Klin | 141600 | Russia |
| GSK Investigational Site | Moscow | 115446 | Russia |
| GSK Investigational Site | Saint Petersburg | 194356 | Russia |
| GSK Investigational Site | Saratov | 410028 | Russia |
| GSK Investigational Site | Voronezh | 394066 | Russia |
| GSK Investigational Site | Yaroslavl | 150003 | Russia |
| 24966061 | Derived | Svedsater H, Jacques L, Goldfrad C, Bleecker ER. Ease of use of the ELLIPTA dry powder inhaler: data from three randomised controlled trials in patients with asthma. NPJ Prim Care Respir Med. 2014 Jun 26;24:14019. doi: 10.1038/npjpcrm.2014.19. No abstract available. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 115283 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115283 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115283 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115283 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115283 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115283 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. |
| Safety Population |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. |
| BG001 | FF 50 µg OD | Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Gender | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline in Clinic Visit Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-week Treatment Period | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Evening clinic visit FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the Week 12 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were measured electronically by spirometry in the evening at the Baseline through Week 12 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing, pre-dose, post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing value. | Intent-to-Treat (ITT) Population: all participants (par.) randomized to treatment who received >=1 dose of study medication, except for the par. of one investigator (excluded after good clinical practice [GCP] issues identified during a site audit). Only those par. with non-missing covariates and a post-Baseline FEV1 measurement were analyzed. | Posted | Least Squares Mean | Standard Error | Liters | Baseline and Week 12 |
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| Secondary | Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Over the 12-week Treatment Period | The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. A 24-hour period was considered as missing if both day time and night time values were missing or if one of the day time or night time values were missing and the other value indicated no use of rescue medication. The Baseline value is the average of the values over the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Percentage of rescue-free 24-hr periods | From Baseline up to Week 12 |
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| Secondary | Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period | PEF is a measure of lung function and 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 and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Liters/minute (L/min) | From Baseline up to Week 12 |
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| Secondary | Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period | PEF is a measure of lung function and 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 and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | L/min | From Baseline up to Week 12 |
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| Secondary | Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over 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 peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. A 24-hour period was considered as missing if both the day time and night time data were missing or if one was symptom-free but the other was missing. The Baseline value was the average of the values of the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Percentage of symptom-free 24-hr periods | From Baseline up to Week 12 |
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| Secondary | Number of Participants Who Withdrew Due to a Lack of Efficacy During the 12-week Treatment Period | The reason for withdrawal was lack of efficacy if a participant was withdrawn due to: clinic FEV1 falling below the FEV1 stability limit; participant experiencing at least 4 days of AM or PM PEF falling below the PEF stability limit and/or at least 3 days of >=12 inhalations/day of albuterol/salbutamol usage during the 7 days immediately preceding any contact; or the occurrence of an asthma exacerbation, defined as the deterioration of asthma requiring the use of systemic (oral, parenteral, or depot) corticosteroids for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. The FEV1 stability limit was calculated as the best pre-salbutamol/albuterol FEV1 at Visit 2 * 80%. The PEF stability limit was calculated as the mean AM PEF from the available 7 consecutive days preceding Visit 2 * 80%. | ITT Population | Posted | Number | Participants | From the first dose of the study medication until Week 12/Early Withdrawal |
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On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported.
Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. | 1 | 121 | 27 | 121 | ||
| EG001 | FF 50 µg OD | Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. | 1 | 121 | 18 | 121 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis perforated | Infections and infestations | MedDRA | Systematic Assessment |
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| Multiple injuries | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C523187 | fluticasone furoate |
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| Male |
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| American Indian or Alaska Native |
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| Asian |
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| White |
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| African American/African Heritage & White |
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| American Indian or Alaska Native & White |
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Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed. |
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Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
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