Asthma
Conditions
Brief 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.
Interventions
DRUGFluticasone Propionate
Fluticasone propionate
DRUGPlacebo
placebo
DRUGFluticasone Furoate
current asthma medicine
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline; Week 1 up to 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period | Baseline; Week 1 up to Week 12 | 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. |
| Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period | Baseline; Week 1 up to 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 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. |
| Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12) | Baseline; 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. |
| 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 | Baseline, Week 12 | 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. |
| Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period | Baseline; Week 1 up to Week 12 | 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. |
| Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period | Up to Week 12 | 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. |
| Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12) | Baseline; 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. |
Countries
Bulgaria, Georgia, Germany, Japan, Latvia, Mexico, Peru, Philippines, Poland, Puerto Rico, Russia, South Africa, Sweden, Ukraine, United States
Participant flow
Recruitment details
1540 participants were screened, 596 participants were randomized, and 593 participants comprise the Intent to Treat Population which include all participants who received at least one dose of study treatment. Participants were stratified at randomization according to their prior inhaled corticosteroid (ICS) use.
Pre-assignment details
Participants who met the eligibility criteria at screening (Visit 1) entered a 4-week Run-in Period during which they continued their existing medications. Participants who met the randomization criteria (remained uncontrolled despite baseline therapy) at Visit 3 were randomized to 1 of 5 treatment arms for 12 weeks followed by a 1-week follow-up.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo once daily (OD) in the evening via a dry powder inhaler (DPI) and placebo twice daily (BID), once in the morning and once in the evening via a separate DPI for 12 weeks. Participants were also provided albuterol/salbutamol inhalation aerosol via metered dose inhaler (MDI) to be used as rescue medication as determined by the investigator. | 119 |
| FF 25 µg OD Participants received fluticasone furoate (FF) 25 micrograms (µg) OD in the evening via a DPI and placebo BID, once in the morning and once in the evening via a separate DPI for 12 weeks. Participants were also provided albuterol/salbutamol inhalation aerosol via metered dose inhaler (MDI) to be used as rescue medication as determined by the investigator. | 118 |
| FF 50 µg OD Participants received FF 50 µg OD in the evening via a DPI and placebo BID, once in the morning and once in the evening via a separate DPI for 12 weeks. Participants were also provided albuterol/salbutamol inhalation aerosol via metered dose inhaler (MDI) to be used as rescue medication as determined by the investigator. | 120 |
| FF 100 µg OD Participants received FF 100 µg OD in the evening via a DPI and placebo BID, once in the morning and once in the evening via a separate DPI for 12 weeks. Participants were also provided albuterol/salbutamol inhalation aerosol via metered dose inhaler (MDI) to be used as rescue medication as determined by the investigator. | 118 |
| FP 100 µg BID Participants received fluticasone propionate (FP) 100 µg BID, once in the morning and once in the evening via a DPI and placebo OD in the evening via a separate DPI for 12 weeks. Participants were also provided albuterol/salbutamol inhalation aerosol via metered dose inhaler (MDI) to be used as rescue medication as determined by the investigator. | 118 |
| Total | 593 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 2 | 1 |
| Overall Study | Lack of Efficacy | 42 | 16 | 23 | 21 | 19 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 1 | 1 |
| Overall Study | Physician Decision | 3 | 5 | 2 | 4 | 2 |
| Overall Study | Protocol defined stopping criteria | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 3 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 3 | 4 | 3 |
Baseline characteristics
| Characteristic | Placebo | FF 25 µg OD | FF 50 µg OD | FF 100 µg OD | FP 100 µg BID | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 8.0 Years STANDARD_DEVIATION 1.91 | 7.9 Years STANDARD_DEVIATION 2.08 | 8.4 Years STANDARD_DEVIATION 1.62 | 7.8 Years STANDARD_DEVIATION 2.04 | 7.9 Years STANDARD_DEVIATION 1.87 | 8.0 Years STANDARD_DEVIATION 1.92 |
| Race/Ethnicity, Customized African American/African Heritage | 4 Participants | 4 Participants | 7 Participants | 8 Participants | 7 Participants | 30 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 24 Participants | 17 Participants | 16 Participants | 17 Participants | 21 Participants | 95 Participants |
| Race/Ethnicity, Customized Asian -Central/South Asian Heritage | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 7 Participants | 7 Participants | 5 Participants | 2 Participants | 7 Participants | 28 Participants |
| Race/Ethnicity, Customized Mixed Race | 35 Participants | 33 Participants | 40 Participants | 39 Participants | 40 Participants | 187 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 47 Participants | 55 Participants | 51 Participants | 51 Participants | 43 Participants | 247 Participants |
| Sex: Female, Male Female | 49 Participants | 41 Participants | 46 Participants | 48 Participants | 39 Participants | 223 Participants |
| Sex: Female, Male Male | 70 Participants | 77 Participants | 74 Participants | 70 Participants | 79 Participants | 370 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 119 | 27 / 118 | 20 / 120 | 29 / 118 | 24 / 118 |
| serious Total, serious adverse events | 0 / 119 | 0 / 118 | 1 / 120 | 1 / 118 | 0 / 118 |
Outcome results
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.
Time frame: Baseline; Week 1 up to Week 12
Population: ITT Population: participants randomized to treatment who received at least 1 dose of study medication. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | 3.3 Liters per minute (L/min) | Standard Deviation 2.63 |
| FF 25 µg OD | 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 | 21.9 Liters per minute (L/min) | Standard Deviation 2.66 |
| FF 50 µg OD | 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 | 22.8 Liters per minute (L/min) | Standard Deviation 2.65 |
| FF 100 µg OD | 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 | 15.8 Liters per minute (L/min) | Standard Deviation 2.64 |
| FP 100 µg BID | 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 | 17.3 Liters per minute (L/min) | Standard Deviation 2.64 |
| Average of FF 50 µg OD and FF 100 µg OD | 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 | 19.3 Liters per minute (L/min) | Standard Deviation 1.86 |
p-value: <0.00195% CI: [9.6, 22.4]ANCOVA
p-value: <0.00195% CI: [5.1, 19.8]ANCOVA
p-value: <0.00195% CI: [12.1, 26.9]ANCOVA
p-value: <0.00195% CI: [11.3, 26]ANCOVA
p-value: <0.00195% CI: [6.7, 21.4]ANCOVA
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.
Time frame: Baseline; Week 12
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 2.7 L/min | Standard Error 3.81 |
| FF 25 µg OD | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 23.3 L/min | Standard Error 3.85 |
| FF 50 µg OD | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 20.6 L/min | Standard Error 3.83 |
| FF 100 µg OD | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 14.2 L/min | Standard Error 3.82 |
| FP 100 µg BID | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 19.3 L/min | Standard Error 3.82 |
p-value: <0.00195% CI: [10, 31.3]ANCOVA
p-value: 0.00195% CI: [7.2, 28.6]ANCOVA
p-value: 0.03395% CI: [0.9, 22.1]ANCOVA
p-value: 0.00295% CI: [6, 27.3]ANCOVA
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.
Time frame: Baseline; Week 1 up to Week 12
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period | 5.1 liters per minute (L/min) | Standard Error 2.76 |
| FF 25 µg OD | Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period | 16.3 liters per minute (L/min) | Standard Error 2.81 |
| FF 50 µg OD | Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period | 18.5 liters per minute (L/min) | Standard Error 2.77 |
| FF 100 µg OD | Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period | 13.5 liters per minute (L/min) | Standard Error 2.78 |
| FP 100 µg BID | Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period | 13.1 liters per minute (L/min) | Standard Error 2.77 |
p-value: 0.00595% CI: [3.4, 19]ANCOVA
p-value: <0.00195% CI: [5.7, 21.1]ANCOVA
p-value: <0.03395% CI: [0.7, 16.1]ANCOVA
p-value: 0.04295% CI: [0.3, 15.7]ANCOVA
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.
Time frame: Baseline, Week 12
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | 0.128 Liters | Standard Error 0.0264 |
| FF 25 µg OD | 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 | 0.254 Liters | Standard Error 0.0272 |
| FF 50 µg OD | 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 | 0.150 Liters | Standard Error 0.0252 |
| FF 100 µg OD | 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 | 0.162 Liters | Standard Error 0.0272 |
| FP 100 µg BID | 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 | 0.192 Liters | Standard Error 0.0262 |
p-value: <0.00195% CI: [0.051, 0.201]ANCOVA
p-value: 0.55195% CI: [-0.05, 0.094]ANCOVA
p-value: 0.37995% CI: [-0.041, 0.108]ANCOVA
p-value: 0.08995% CI: [-0.01, 0.137]ANCOVA
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.
Time frame: Baseline; Week 12
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 5.0 L/min | Standard Error 3.75 |
| FF 25 µg OD | Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 16.2 L/min | Standard Error 3.8 |
| FF 50 µg OD | Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 18.2 L/min | Standard Error 3.77 |
| FF 100 µg OD | Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 11.0 L/min | Standard Error 3.76 |
| FP 100 µg BID | Change From Baseline in PM PEF Over the Last 7 Days of the Treatment Period (Week 12) | 11.3 L/min | Standard Error 3.75 |
p-value: 0.03795% CI: [0.7, 21.7]ANCOVA
p-value: 0.01495% CI: [2.6, 23.6]ANCOVA
p-value: 0.26695% CI: [-4.5, 16.3]ANCOVA
p-value: 0.24295% CI: [-4.2, 16.6]ANCOVA
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.
Time frame: Baseline; Week 1 up to Week 12
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period | 16.5 Percentage of rescue-free 24-hr periods | Standard Error 3.01 |
| FF 25 µg OD | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period | 24.9 Percentage of rescue-free 24-hr periods | Standard Error 3.03 |
| FF 50 µg OD | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period | 26.3 Percentage of rescue-free 24-hr periods | Standard Error 3.03 |
| FF 100 µg OD | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period | 28.7 Percentage of rescue-free 24-hr periods | Standard Error 3.02 |
| FP 100 µg BID | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 12-week Treatment Period | 22.7 Percentage of rescue-free 24-hr periods | Standard Error 3.01 |
p-value: 0.0595% CI: [0, 16.9]ANCOVA
p-value: 0.02395% CI: [1.3, 18.2]ANCOVA
p-value: 0.00495% CI: [3.8, 20.5]ANCOVA
p-value: 0.14395% CI: [-2.1, 14.6]ANCOVA
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.
Time frame: Baseline; Week 1 up to Week 12
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period | 19.0 Percentage of symptom-free 24-hr periods | Standard Error 2.9 |
| FF 25 µg OD | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period | 21.0 Percentage of symptom-free 24-hr periods | Standard Error 2.92 |
| FF 50 µg OD | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period | 24.7 Percentage of symptom-free 24-hr periods | Standard Error 2.9 |
| FF 100 µg OD | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period | 22.9 Percentage of symptom-free 24-hr periods | Standard Error 2.91 |
| FP 100 µg BID | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 12-week Treatment Period | 22.0 Percentage of symptom-free 24-hr periods | Standard Error 2.91 |
p-value: 0.61995% CI: [-6.1, 10.2]ANCOVA
p-value: 0.16195% CI: [-2.3, 13.9]ANCOVA
p-value: 0.3495% CI: [-4.1, 12]ANCOVA
p-value: 0.45995% CI: [-5, 11.1]ANCOVA
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.
Time frame: Up to Week 12
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period | 42 Participants |
| FF 25 µg OD | Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period | 16 Participants |
| FF 50 µg OD | Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period | 23 Participants |
| FF 100 µg OD | Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period | 21 Participants |
| FP 100 µg BID | Number of Withdrawals Due to Lack of Efficacy Throughout the 12-week Treatment Period | 19 Participants |
p-value: <0.001Fisher Exact
p-value: 0.006Fisher Exact
p-value: 0.003Fisher Exact
p-value: <0.001Fisher Exact