Asthma
Conditions
Brief summary
This study will establish the safety as well as demonstrate benefit of the addition of a LABA to an ICS by utilizing an endpoint (time to first severe asthma exacerbation) that informs on both safety and efficacy.
Interventions
Combination inhaled corticosteroid and long-acting beta2-agonist
DRUGFluticasone furoate
Inhaled corticosteroid
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of asthma * Reversibility FEV1 of twelve percent or greater and two hundred milliliters and greater approximately ten to forty minutes following two to four inhalations of albuterol * FEV1 of fifty to ninety percent of predicted * Currently using inhaled corticosteroid therapy * History of one or more asthma exacerbations requiring treatment with oral/systemic corticosteroids or emergency department visit or in-patient hospitalization in previous year
Exclusion criteria
* History of life threatening asthma in previous 5 years (requiring intubation, and/or associated with hypercapnia, hypoxic seizure or respiratory arrest * Respiratory infection or oral candidiasis * \- Uncontrolled disease or clinical abnormality * Allergies * Taking another investigational medication or prohibited medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 1 or More Severe Asthma Exacerbations | Baseline to Follow-up (up to 76 weeks of treatment) | Asthma is a medical condition that causes narrowing of the small airways in the lungs. A severe asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Only events deemed by the adjudication committee to be severe asthma exacerbations were used in the analysis of severe asthma exacerbations. The time to the first severe asthma exacerbation was analyzed using a Cox proportional hazards regression model, adjusting for Baseline disease severity (Baseline forced expiratory volume in one second \[FEV1, maximum amount of air forcefully exhaled in one second\]), sex, age, and region. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Severe Asthma Exacerbations | Baseline to Follow-up (up to 76 weeks of treatment) | A severe asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. A participant may have had one or more exacerbations. |
| Change From Baseline in Evening Pre-dose Trough FEV1 at Week 36 | Baseline and Week 36 | Evening pre-dose trough (lowest value) forced expiratory volume in one second (FEV1) was measured using spirometry equipment that met or exceeded the minimal performance recommendations of the American Thoracic Society. FEV1 is a measure of the maximum amount of air forcefully exhaled in one second. Change from Baseline in evening pre-dose FEV1 was analyzed using an Analysis of Covariance (ANCOVA) model with effects due to Baseline FEV1, sex, age, region, and treatment. Change from Baseline was calculated as the Week 36 value minus the Baseline value. |
Countries
Argentina, Australia, Germany, Japan, Mexico, Philippines, Poland, Romania, Russia, Ukraine, United States
Participant flow
Pre-assignment details
Participants (par.) who met all entry criteria at Screening entered a 2-week Run-in Period for completion of Baseline safety evaluations and to obtain Baseline measures of asthma status. Participants who met continuation criteria at the end of the Run-in Period were randomized to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| FF 100 µg Participants received fluticasone furoate (FF) 100 microgram (µg) inhalation powder via a dry powder inhaler (DPI) once daily in the evening. Short-acting beta2-agonist inhalation aerosol (albuterol/salbutamol) was provided to be used as needed for symptomatic relief of asthma symptoms during the Treatment Period. | 1,010 |
| FF/VI 100/25 µg Participants received FF/vilanterol (VI) 100/25 µg inhalation powder via a DPI once daily in the evening. Short-acting beta2-agonist inhalation aerosol (albuterol/salbutamol) was provided to be used as needed for symptomatic relief of asthma symptoms during the Treatment Period. | 1,009 |
| Total | 2,019 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 2-week Run-in Period | Adverse Event | 1 | 0 | 0 |
| 2-week Run-in Period | Continuation Criteria Not Met | 92 | 0 | 0 |
| 2-week Run-in Period | Lost to Follow-up | 1 | 0 | 0 |
| 2-week Run-in Period | Physician Decision | 6 | 0 | 0 |
| 2-week Run-in Period | Protocol Violation | 1 | 0 | 0 |
| 2-week Run-in Period | Randomized in Error | 1 | 0 | 0 |
| 2-week Run-in Period | Study Closed/Terminated | 42 | 0 | 0 |
| 2-week Run-in Period | Withdrawal by Subject | 19 | 0 | 0 |
| Treatment Period | Adverse Event | 0 | 19 | 15 |
| Treatment Period | Lack of Efficacy | 0 | 22 | 13 |
| Treatment Period | Lost to Follow-up | 0 | 11 | 9 |
| Treatment Period | Physician Decision | 0 | 9 | 6 |
| Treatment Period | Protocol-Defined Stopping Criteria | 0 | 0 | 1 |
| Treatment Period | Protocol Violation | 0 | 26 | 17 |
| Treatment Period | Received Treatment in Error | 0 | 1 | 0 |
| Treatment Period | Study Closed/Terminated | 0 | 7 | 8 |
| Treatment Period | Withdrawal by Subject | 0 | 53 | 55 |
Baseline characteristics
| Characteristic | FF/VI 100/25 µg | Total | FF 100 µg |
|---|---|---|---|
| Age, Continuous | 41.1 Years STANDARD_DEVIATION 17.1 | 41.7 Years STANDARD_DEVIATION 16.96 | 42.3 Years STANDARD_DEVIATION 16.82 |
| Race/Ethnicity, Customized African American/African Heritage | 40 participants | 87 participants | 47 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 9 participants | 13 participants | 4 participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 32 participants | 62 participants | 30 participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 78 participants | 157 participants | 79 participants |
| Race/Ethnicity, Customized Mixed Race | 108 participants | 212 participants | 104 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 2 participants | 7 participants | 5 participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 738 participants | 1476 participants | 738 participants |
| Sex: Female, Male Female | 661 Participants | 1350 Participants | 689 Participants |
| Sex: Female, Male Male | 348 Participants | 669 Participants | 321 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 479 / 1,010 | 467 / 1,009 |
| serious Total, serious adverse events | 29 / 1,010 | 41 / 1,009 |
Outcome results
Primary
Number of Participants With 1 or More Severe Asthma Exacerbations
Asthma is a medical condition that causes narrowing of the small airways in the lungs. A severe asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Only events deemed by the adjudication committee to be severe asthma exacerbations were used in the analysis of severe asthma exacerbations. The time to the first severe asthma exacerbation was analyzed using a Cox proportional hazards regression model, adjusting for Baseline disease severity (Baseline forced expiratory volume in one second \[FEV1, maximum amount of air forcefully exhaled in one second\]), sex, age, and region.
Time frame: Baseline to Follow-up (up to 76 weeks of treatment)
Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF 100 µg | Number of Participants With 1 or More Severe Asthma Exacerbations | 186 participants |
| FF/VI 100/25 µg | Number of Participants With 1 or More Severe Asthma Exacerbations | 154 participants |
95% CI: [0.642, 0.985]
p-value: 0.03695% CI: [13.5, 18.2]Regression, Cox
p-value: 0.03695% CI: [10.7, 14.9]Regression, Cox
Secondary
Change From Baseline in Evening Pre-dose Trough FEV1 at Week 36
Evening pre-dose trough (lowest value) forced expiratory volume in one second (FEV1) was measured using spirometry equipment that met or exceeded the minimal performance recommendations of the American Thoracic Society. FEV1 is a measure of the maximum amount of air forcefully exhaled in one second. Change from Baseline in evening pre-dose FEV1 was analyzed using an Analysis of Covariance (ANCOVA) model with effects due to Baseline FEV1, sex, age, region, and treatment. Change from Baseline was calculated as the Week 36 value minus the Baseline value.
Time frame: Baseline and Week 36
Population: ITT Population. Only those participants available at the indicated time point (Week 36) were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF 100 µg | Change From Baseline in Evening Pre-dose Trough FEV1 at Week 36 | 0.265 Liters | Standard Deviation 0.014 |
| FF/VI 100/25 µg | Change From Baseline in Evening Pre-dose Trough FEV1 at Week 36 | 0.348 Liters | Standard Deviation 0.014 |
Secondary
Number of Severe Asthma Exacerbations
A severe asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. A participant may have had one or more exacerbations.
Time frame: Baseline to Follow-up (up to 76 weeks of treatment)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF 100 µg | Number of Severe Asthma Exacerbations | 271 Severe asthma exacerbations |
| FF/VI 100/25 µg | Number of Severe Asthma Exacerbations | 200 Severe asthma exacerbations |