Asthma
Conditions
Brief summary
This is a Phase IIb, multi-centre, randomised, double-blind, parallel-group, placebo-controlled study in children aged 5-11 years with persistent uncontrolled asthma. Subjects entering the run-in period will stop their current asthma medication and be given open label fluticasone propionate (FP) 100mcg twice daily via DISKUS/ACCUHALER and salbutamol/albuterol as required to use throughout the run-in and double-blind treatment period. At Visit 3 subjects meeting the randomization eligibility criteria will receive vilanterol (6.25mcg, 12.5mcg, or 25mcg,) or placebo via the Novel Dry Powder Inhaler (NDPI) once daily for 4 weeks in addition to open-label fluticasone propionate twice daily throughout the treatment period. Primary endpoints consist of change from baseline in clinic visit trough (pre-bronchodilator and pre-dose) PEF at the end of the 28-day treatment period in all subjects. Safety assessments include adverse events, oropharyngeal examinations, clinical chemistry, 12-lead ECG, and vital signs. Blood samples will be taken from all subjects for pharmacokinetic analysis to determine plasma concentrations of vilanterol at specific time intervals relative to the dose of study drug.
Interventions
all subjects recieve open-label Flovent twice daily duirng the run in and treatment period
DRUGPlacebo
Placebo inhalation powder during treatment period
DRUGVilanterol
subjects will recieve 4 weeks via NDPI during treament period
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, 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 stable asthma therapy of short acting beta-agonist (SABA) plus ICS (total daily dose FP 200mcg or equivalent)
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 Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-week Treatment Period | Baseline; Week 1 up to Week 4 | 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 each morning. The best of three measurements was recorded. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 4-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 Phase. The analysis was performed using an analysis of covariance (ANCOVA) model with covariates of Baseline, region, sex, age, and treatment. Only those participants contributing data per the daily eDiary were analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 4-week Treatment Period in Children Who Could Perform the Maneuver | Baseline; Week 4 | 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 in trough FEV1 at the end of the 4-week Treatment Period was defined using the pre-dose FEV1 measurement taken at the Week 4 clinic visit. Change from Baseline was calculated as the Week 4 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, 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. |
| Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 4-week Treatment Period | Baseline; Week 1 up to Week 4 | The number of inhalations of rescue albuterol/salbutamol inhalation 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 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. Participants who were rescue free for 24-hour periods during the 4-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline is calculated as the average value during the 4-week Treatment Period minus the value at Baseline. The Baseline value is defined as the value at Visit 3 (randomization). Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. |
| Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-week Treatment Period | Baseline; Week 1 up to Week 4 | 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. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 4-week Treatment Period (at Week 4) minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. |
| Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4) | Baseline; Week 4 | 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 is calculated as the value over the last 7 days of the Treatment Period minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. The 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. |
| Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 4) | Baseline; Week 4 | 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. Change from Baseline is calculated as the value of the averaged daily AM PEF over the 4-week Treatment Period (at Week 4) minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. |
| Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 4-week Treatment Period | Baseline; Week 1 up to Week 4 | 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 value at Visit 3 (randomization). Change from Baseline was calculated as the averaged value during the 4-week Treatment Period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. |
Countries
Argentina, Chile, Georgia, Germany, Japan, Mexico, Peru, Philippines, Poland, Puerto Rico, Slovakia, South Africa, Ukraine, United States
Participant flow
Recruitment details
1208 participants (par.) were screened; 760 entered the Run-in Phase, 463 were randomized, and 2 received study medication (SM) but weren't randomized/included in the Intent-to-Treat (ITT) Population (randomized to treatment and receiving \>=1 SM dose). 7 randomized par. didn't receive SM; hence, 456 par. comprised the ITT Population.
Pre-assignment details
Participants who met the eligibility criteria at screening (Visit 1) entered the Run-in Phase for completion of Baseline safety evaluations and measures of asthma status. Participants meeting all randomization criteria at Visit 3 were randomized to 1 of 4 treatment arms. The total duration of study participation was up to a maximum of 9 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo once daily (OD) in the evening from a dry powder inhaler for 4 weeks in addition to open-label fluticasone propionate (FP) 100 micrograms (µg) twice daily (BID). Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication. | 115 |
| VI 6.25 µg OD Participants received vilanterol (VI) 6.25 µg OD in the evening from a dry powder inhaler for 4 weeks in addition to open-label FP 100 µg BID. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication. | 114 |
| VI 12.5 µg OD Participants received VI 12.5 µg OD in the evening from a dry powder inhaler for 4 weeks in addition to open-label FP 100 µg BID. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication. | 113 |
| VI 25 µg OD Participants received VI 25 µg OD in the evening from a dry powder inhaler for 4 weeks in addition to open-label FP 100 µg BID. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication. | 114 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 18 | 15 | 12 | 17 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 2 | 0 | 2 |
| Overall Study | Protocol Violation | 3 | 1 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | VI 6.25 µg OD | VI 12.5 µg OD | VI 25 µg OD | Total |
|---|---|---|---|---|---|
| Age, Continuous | 8.0 Years STANDARD_DEVIATION 1.81 | 8.0 Years STANDARD_DEVIATION 1.95 | 7.9 Years STANDARD_DEVIATION 1.74 | 7.9 Years STANDARD_DEVIATION 1.72 | 7.9 Years STANDARD_DEVIATION 1.8 |
| Gender Female | 50 Participants | 43 Participants | 42 Participants | 45 Participants | 180 Participants |
| Gender Male | 65 Participants | 71 Participants | 71 Participants | 69 Participants | 276 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 18 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 16 Participants | 21 Participants | 17 Participants | 18 Participants | 72 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 20 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Mixed Race | 20 Participants | 19 Participants | 29 Participants | 25 Participants | 93 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 67 Participants | 62 Participants | 55 Participants | 61 Participants | 245 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 115 | 17 / 114 | 12 / 113 | 11 / 114 |
| serious Total, serious adverse events | 0 / 115 | 0 / 114 | 0 / 113 | 1 / 114 |
Outcome results
Primary
Change From Baseline in Daily Pre-dose Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-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 each morning. The best of three measurements was recorded. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 4-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 Phase. The analysis was performed using an analysis of covariance (ANCOVA) model with covariates of Baseline, region, sex, age, and treatment. Only those participants contributing data per the daily eDiary were analyzed.
Time frame: Baseline; Week 1 up to Week 4
Population: ITT Population: participants randomized to treatment who received \>=1 dose of study medication
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Pre-dose Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-week Treatment Period | 215.9 Liters per minute (L/min) | Standard Error 2.53 |
| VI 6.25 µg OD | Change From Baseline in Daily Pre-dose Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-week Treatment Period | 221.4 Liters per minute (L/min) | Standard Error 2.53 |
| VI 12.5 µg OD | Change From Baseline in Daily Pre-dose Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-week Treatment Period | 222.4 Liters per minute (L/min) | Standard Error 2.54 |
| VI 25 µg OD | Change From Baseline in Daily Pre-dose Evening (PM) Peak Expiratory Flow (PEF) From Participant Electronic Daily Diary Averaged Over the 4-week Treatment Period | 220.3 Liters per minute (L/min) | Standard Error 2.56 |
p-value: 0.22795% CI: [-2.7, 11.4]ANCOVA
p-value: 0.07395% CI: [-0.6, 13.5]ANCOVA
p-value: 0.12795% CI: [-1.6, 12.5]ANCOVA
Secondary
Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 4)
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. Change from Baseline is calculated as the value of the averaged daily AM PEF over the 4-week Treatment Period (at Week 4) minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.
Time frame: Baseline; Week 4
Population: ITT Population. Only those 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 4) | 7.4 L/min | Standard Error 3.45 |
| VI 6.25 µg OD | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 4) | 13.3 L/min | Standard Error 3.47 |
| VI 12.5 µg OD | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 4) | 17.0 L/min | Standard Error 3.48 |
| VI 25 µg OD | Change From Baseline in AM PEF Over the Last 7 Days of the Treatment Period (Week 4) | 14.4 L/min | Standard Error 3.51 |
95% CI: [-3.7, 15.6]
95% CI: [0, 19.3]
95% CI: [-2.7, 16.7]
Secondary
Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-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. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 4-week Treatment Period (at Week 4) minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.
Time frame: Baseline; Week 1 up to Week 4
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-week Treatment Period | 6.4 L/min | Standard Error 2.42 |
| VI 6.25 µg OD | Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-week Treatment Period | 12.0 L/min | Standard Error 2.43 |
| VI 12.5 µg OD | Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-week Treatment Period | 13.9 L/min | Standard Error 2.44 |
| VI 25 µg OD | Change From Baseline in Daily Morning (AM) PEF Averaged Over the 4-week Treatment Period | 13.7 L/min | Standard Error 2.46 |
95% CI: [-1.2, 12.3]
95% CI: [0.7, 14.2]
95% CI: [0.4, 14]
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 4-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 in trough FEV1 at the end of the 4-week Treatment Period was defined using the pre-dose FEV1 measurement taken at the Week 4 clinic visit. Change from Baseline was calculated as the Week 4 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, 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.
Time frame: Baseline; Week 4
Population: ITT Population. Only those 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 4-week Treatment Period in Children Who Could Perform the Maneuver | 0.223 Liters | Standard Error 0.0287 |
| VI 6.25 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 4-week Treatment Period in Children Who Could Perform the Maneuver | 0.166 Liters | Standard Error 0.0292 |
| VI 12.5 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 4-week Treatment Period in Children Who Could Perform the Maneuver | 0.240 Liters | Standard Error 0.0285 |
| VI 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 4-week Treatment Period in Children Who Could Perform the Maneuver | 0.193 Liters | Standard Error 0.0288 |
95% CI: [-0.138, 0.024]
95% CI: [-0.063, 0.096]
95% CI: [-0.11, 0.051]
Secondary
Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4)
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 is calculated as the value over the last 7 days of the Treatment Period minus the Baseline value. The Baseline value is defined as the value at Visit 3 (randomization). The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. The 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.
Time frame: Baseline; Week 4
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4) | 5.9 L/min | Standard Error 3.44 |
| VI 6.25 µg OD | Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4) | 9.4 L/min | Standard Error 3.44 |
| VI 12.5 µg OD | Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4) | 13.7 L/min | Standard Error 3.45 |
| VI 25 µg OD | Change From Baseline in Evening (PM) PEF Over the Last 7 Days of the Treatment Period (Week 4) | 11.1 L/min | Standard Error 3.48 |
95% CI: [-6.1, 13.1]
95% CI: [-1.8, 17.4]
95% CI: [-4.4, 14.9]
Secondary
Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 4-week Treatment Period
The number of inhalations of rescue albuterol/salbutamol inhalation 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 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. Participants who were rescue free for 24-hour periods during the 4-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline is calculated as the average value during the 4-week Treatment Period minus the value at Baseline. The Baseline value is defined as the value at Visit 3 (randomization). Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
Time frame: Baseline; Week 1 up to Week 4
Population: ITT population. Only those 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 4-week Treatment Period | 14.4 Percentage of rescue-free 24-hr periods | Standard Error 2.97 |
| VI 6.25 µg OD | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 4-week Treatment Period | 12.2 Percentage of rescue-free 24-hr periods | Standard Error 2.97 |
| VI 12.5 µg OD | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 4-week Treatment Period | 15.8 Percentage of rescue-free 24-hr periods | Standard Error 2.98 |
| VI 25 µg OD | Change From Baseline in the Percentage of Rescue-free 24-hour Periods During the 4-week Treatment Period | 2.98 Percentage of rescue-free 24-hr periods | Standard Error 3.01 |
95% CI: [-10.5, 6]
95% CI: [-6.9, 9.6]
95% CI: [0.4, 17]
Secondary
Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 4-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 value at Visit 3 (randomization). Change from Baseline was calculated as the averaged value during the 4-week Treatment Period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.
Time frame: Baseline; Week 1 up to Week 4
Population: ITT Population. Only those 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 4-week Treatment Period | 9.9 Percentage of symptom-free 24-hr periods | Standard Error 2.65 |
| VI 6.25 µg OD | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 4-week Treatment Period | 10.1 Percentage of symptom-free 24-hr periods | Standard Error 2.65 |
| VI 12.5 µg OD | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 4-week Treatment Period | 18.3 Percentage of symptom-free 24-hr periods | Standard Error 2.66 |
| VI 25 µg OD | Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the 4-week Treatment Period | 19.7 Percentage of symptom-free 24-hr periods | Standard Error 2.69 |
95% CI: [-7.2, 7.5]
95% CI: [1, 15.7]
95% CI: [2.3, 17.2]