Asthma
Conditions
Keywords
Pediatric, asthma, albuterol-HFA and Placebo
Brief summary
The primary objective of this study is to evaluate the chronic-dose and efficacy of Albuterol-HFA-MDI relative to placebo in pediatric asthmatics.
Interventions
DRUGAlbuterol
Albuterol HFA MDI 180 mcg four times a day (q.i.d) for a total daily albuterol dose of 720 mcg for 21 days.
DRUGPlacebo
Placebo HFA MDI four times a day (q.i.d) for 21 days.
DRUGProventil® HFA
Proventil® HFA (albuterol sulfate) Inhalation Aerosol (Key Pharmaceuticals) was used as rescue medication in this study. The rescue medication was over-labeled with instructions for emergency use in which subjects were instructed to self-administer up to two puffs every 20 minutes to a maximum of six puffs for any given episode while attempting to seek medical assistance.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male and female child aged 4-11 years, inclusive Asthma of a minimum of six months duration that has been stable for at least four weeks prior to screening.
Exclusion criteria
* Hospitalization for acute asthma exacerbation greater than two years in 12 months prior to screening and/or received ER treatment or hospitalization for asthma exacerbation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22 | 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing on Day 22 or last observation | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age. |
| Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22 | 30±5 and 5±2 minutes prior to dosing, and at 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing on Day 22 or last observation | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Baseline (Day 1 or Day 22: 35±5 and 10±2 minutes prior to dosing), Day 22 (5±2, 15±5, 30±5, 45±5, 60±10, 120±10, 240±10, and 360±10 minutes post-dosing or last observation) | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria. The area under-the-effect curves for percent-predicted FEV1 were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times. |
| Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Baseline (Day 1 or Day 22: 30±5 and 5±2 minutes prior to dosing Day 22: 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing or last observation | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. The area under-the-effect curves for PEF were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times. |
| Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) | Days 1 and 22: 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria. |
| Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Time to maximum FEV1 is defined as the number of minutes required for the baseline FEV1 to increase to the highest FEV1 post dose during the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day. |
| Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 | Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. Time to maximum PEF is defined as the number of minutes required for the baseline PEF to increase to the highest PEF post-dose for the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day. |
| Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a \>+15% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. |
| Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using test day baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. |
| Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a \>+15% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values. |
| Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a \>+12% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values. |
| Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Weeks 1, 2, 3 | Highest daily asthma symptom scores by study week. For this assessment, patients self-evaluate and record on the diary card the following asthma symptoms experienced during the day (i.e. last 12-14 hours): wheeze, shortness of breath, cough, tightness of chest. The worst of these symptoms were scored daily on a four-point scale: * 0 = No symptoms occurred * 1 = Symptom occurred but did not interfere with daily activity * 2 = Symptom occurred but was sometimes annoying or interfered with daily activity * 3 = Symptom present even at rest and was annoying or interfered with daily activity |
| The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Run-in (Days -21 to -1), Weeks 1, 2, 3 | Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night. |
| Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Weeks 1, 2, 3 | Participants measured their PEF as trained by taking as deep a breath as possible, placing their mouth firmly around the mouthpiece of the flow meter to form a tight seal, and exhaling as hard and as fast as possible. Subjects repeated the process twice at intervals of approximately 30 seconds, and then recorded the highest of the three PEF values on the diary card. |
| Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Weeks 1, 2, 3 | Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night and the number of puffs of rescue albuterol used during the night after going to bed. At the end of each day, the number of puffs of albuterol rescue medication used during the day were recorded. |
| Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing | The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a \>+12% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. |
| Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases | Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing | The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing on study days 1 and 22. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age. |
Countries
United States
Participant flow
Pre-assignment details
208 individual subjects were screened; ten subjects failed the initial screening but were later re-screened and successfully enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Albuterol Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. | 52 |
| Placebo Placebo HFA-MDI four times a day for 21 days. | 51 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Patient Request | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Albuterol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 8.3 Years STANDARD_DEVIATION 1.82 | 8.2 Years STANDARD_DEVIATION 2.09 | 8.2 Years STANDARD_DEVIATION 1.95 |
| Forced Expiratory Volume in One Second (FEV1) on Day 1 | 1.52 liters STANDARD_DEVIATION 0.38 | 1.49 liters STANDARD_DEVIATION 0.46 | 1.50 liters STANDARD_DEVIATION 0.42 |
| Race/Ethnicity, Customized Asian | 5 participants | 3 participants | 8 participants |
| Race/Ethnicity, Customized Black | 14 participants | 7 participants | 21 participants |
| Race/Ethnicity, Customized North American Indian or Alaska native | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Other | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized White | 30 participants | 39 participants | 69 participants |
| Region of Enrollment United States | 52 participants | 51 participants | 103 participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 39 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 52 | 5 / 51 |
| serious Total, serious adverse events | 0 / 52 | 0 / 51 |
Outcome results
Primary
Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.
Time frame: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing on Day 22 or last observation
Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22 | 12.849 percentage change from baseline | Standard Error 1.005 |
| Placebo | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22 | 9.353 percentage change from baseline | Standard Error 1.017 |
Comparison: Efficacy was declared if the test for either primary efficacy endpoint was significant at the 0.025 level.p-value: 0.013895% CI: [0.729, 6.262]ANCOVA
Primary
Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.
Time frame: 30±5 and 5±2 minutes prior to dosing, and at 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing on Day 22 or last observation
Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22 | 17.558 percentage change from baseline | Standard Error 1.878 |
| Placebo | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22 | 12.127 percentage change from baseline | Standard Error 1.907 |
Comparison: Efficacy was declared if the test for either primary efficacy endpoint was significant at the 0.025 level.p-value: 0.040395% CI: [0.244, 10.618]ANCOVA
Secondary
Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. The area under-the-effect curves for PEF were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times.
Time frame: Baseline (Day 1 or Day 22: 30±5 and 5±2 minutes prior to dosing Day 22: 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing or last observation
Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 22 Baseline (n=52, 51) | 120.82 Liters/Minute*Hours | Standard Error 17.486 |
| Albuterol | Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 1 Baseline (n=52, 51) | 139.42 Liters/Minute*Hours | Standard Error 25.782 |
| Placebo | Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 22 Baseline (n=52, 51) | 90.693 Liters/Minute*Hours | Standard Error 17.753 |
| Placebo | Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 1 Baseline (n=52, 51) | 96.842 Liters/Minute*Hours | Standard Error 26.117 |
Comparison: Day 22 Baselinep-value: 0.218695% CI: [-18.169, 78.417]ANCOVA
Comparison: Day 1 Baselinep-value: 0.237595% CI: [-28.541, 113.7]ANCOVA
Secondary
Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria. The area under-the-effect curves for percent-predicted FEV1 were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times.
Time frame: Baseline (Day 1 or Day 22: 35±5 and 10±2 minutes prior to dosing), Day 22 (5±2, 15±5, 30±5, 45±5, 60±10, 120±10, 240±10, and 360±10 minutes post-dosing or last observation)
Population: Intent-To-Treat (ITT) population with Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 22 Baseline (n=52, 51) | 31.046 Percent of Predicted FEV1 * Hours | Standard Error 3.531 |
| Albuterol | Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 1 Baseline (n=51, 51) | 25.060 Percent of Predicted FEV1 * Hours | Standard Error 6.748 |
| Placebo | Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 22 Baseline (n=52, 51) | 21.338 Percent of Predicted FEV1 * Hours | Standard Error 3.588 |
| Placebo | Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines | Day 1 Baseline (n=51, 51) | 24.167 Percent of Predicted FEV1 * Hours | Standard Error 6.773 |
Comparison: Day 22 Baselinep-value: 0.050795% CI: [-0.03, 19.445]ANCOVA
Comparison: Day 1 Baselinep-value: 0.92495% CI: [-17.634, 19.419]ANOVA
Secondary
Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using test day baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.
Time frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing
Population: Observed cases (i.e. available data only)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases | Day 1 (n=51, 51) | 12.621 percentage change from baseline | Standard Error 1.072 |
| Albuterol | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases | Day 22 (n=51, 47) | 12.601 percentage change from baseline | Standard Error 1.072 |
| Placebo | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases | Day 1 (n=51, 51) | 8.085 percentage change from baseline | Standard Error 1.075 |
| Placebo | Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases | Day 22 (n=51, 47) | 9.534 percentage change from baseline | Standard Error 1.119 |
Comparison: Day 1~A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to FEV1max%0-2 at Days 1 and 22, with observed case data.p-value: 0.003195% CI: [1.567, 7.505]Mixed Models Analysis
Comparison: Day 22~A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to FEV1max%0-2 at Days 1 and 22, with observed case data.p-value: 0.04795% CI: [0.041, 6.094]Mixed Models Analysis
Secondary
Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs). The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing on study days 1 and 22. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values. The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.
Time frame: Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing
Population: Observed cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases | Day 1 (n=52, 51) | 20.040 percentage change from baseline | Standard Error 1.982 |
| Albuterol | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases | Day 22 (n=51, 47) | 16.776 percentage change from baseline | Standard Error 1.997 |
| Placebo | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases | Day 1 (n=52, 51) | 12.468 percentage change from baseline | Standard Error 2.004 |
| Placebo | Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases | Day 22 (n=51, 47) | 12.994 percentage change from baseline | Standard Error 2.076 |
Comparison: Day 1~A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to PEFmax%0-2 at Days 1 and 22, with observed case data.p-value: 0.007495% CI: [2.077, 13.067]repeated measures ANOVA
Comparison: Day 22~A repeated measures mixed model, with terms for treatment, pooled center, study day, treatment by study day interaction, and baseline as a covariate, and subject as a random term, was used to make comparisons between placebo and active with respect to PEFmax%0-2 at Days 1 and 22, with observed case data.p-value: 0.184395% CI: [-1.832, 9.397]repeated measures ANOVA
Secondary
Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case)
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria.
Time frame: Days 1 and 22: 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing
Population: Observed cases (i.e. available data only)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) | Day 1 (n=51, 51) | 95.898 percentage of predicted FEV1 | Standard Error 1.451 |
| Albuterol | Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) | Day 22 (n=51, 47) | 94.650 percentage of predicted FEV1 | Standard Error 1.451 |
| Placebo | Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) | Day 1 (n=51, 51) | 89.374 percentage of predicted FEV1 | Standard Error 1.462 |
| Placebo | Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) | Day 22 (n=51, 47) | 90.652 percentage of predicted FEV1 | Standard Error 1.488 |
Comparison: Day 1p-value: 0.001795% CI: [2.524, 10.523]ANOVA
Comparison: Day 22p-value: 0.052195% CI: [-0.037, 8.032]ANOVA
Secondary
Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a \>+12% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.
Time frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=51, 51) | 33.3 percentage of participants |
| Albuterol | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 29.4 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=51, 51) | 13.7 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 14.9 percentage of participants |
Comparison: Day 1p-value: 0.0343Fisher Exact
Comparison: Day 22p-value: 0.0962Fisher Exact
Secondary
Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a \>+12% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values.
Time frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=52, 51) | 57.7 percentage of participants |
| Albuterol | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 56.9 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=52, 51) | 25.5 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 29.8 percentage of participants |
Comparison: Day 1p-value: 0.0013Fisher Exact
Comparison: Day 22p-value: 0.0085Fisher Exact
Secondary
Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a \>+15% increase in FEV1 within 30 minutes of dose. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.
Time frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=51, 51) | 17.6 percentage of participants |
| Albuterol | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 17.6 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=51, 51) | 9.8 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 6.4 percentage of participants |
Comparison: Day 1p-value: 0.3888Fisher Exact
Comparison: Day 22p-value: 0.1249Fisher Exact
Secondary
Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a \>+15% increase in PEF within 30 minutes of dose. The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values.
Time frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=52, 51) | 44.2 percentage of participants |
| Albuterol | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 41.2 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 1 (n=52, 51) | 19.6 percentage of participants |
| Placebo | Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 | Day 22 (n=51, 47) | 23.4 percentage of participants |
Comparison: Day 1p-value: 0.0109Fisher Exact
Comparison: Day 22p-value: 0.0845Fisher Exact
Secondary
The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication
Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.
Time frame: Run-in (Days -21 to -1), Weeks 1, 2, 3
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Week 1 (N=51, N=50) | 1.14 awakenings/week | Standard Deviation 3.25 |
| Albuterol | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Week 3 (N=49, N=48) | 0.65 awakenings/week | Standard Deviation 2.21 |
| Albuterol | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Week 2 (N=51, N=49) | 1.16 awakenings/week | Standard Deviation 3.82 |
| Albuterol | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Run-In (N=52, N=51) | 1.15 awakenings/week | Standard Deviation 2.97 |
| Placebo | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Week 1 (N=51, N=50) | 1.00 awakenings/week | Standard Deviation 2.84 |
| Placebo | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Run-In (N=52, N=51) | 1.06 awakenings/week | Standard Deviation 2.44 |
| Placebo | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Week 2 (N=51, N=49) | 0.73 awakenings/week | Standard Deviation 1.97 |
| Placebo | The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication | Week 3 (N=49, N=48) | 1.33 awakenings/week | Standard Deviation 3.13 |
Secondary
Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22
The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Time to maximum FEV1 is defined as the number of minutes required for the baseline FEV1 to increase to the highest FEV1 post dose during the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day.
Time frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing
Population: Intent-To-Treat (ITT) population; Last Observation Carried Forward (LOCF) used for Day 22
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albuterol | Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 | Day 1 (n=51, 51) | 43.95 minutes |
| Albuterol | Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 | Day 22 with LOCF (n=52, 51) | 41.54 minutes |
| Placebo | Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 | Day 1 (n=51, 51) | 45.25 minutes |
| Placebo | Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 | Day 22 with LOCF (n=52, 51) | 61.05 minutes |
Comparison: Day 1p-value: 0.064795% CI: [0.98, 2.23]Regression, Cox
Comparison: Day 22p-value: 0.000595% CI: [1.38, 3.15]Regression, Cox
Secondary
Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22
The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. Time to maximum PEF is defined as the number of minutes required for the baseline PEF to increase to the highest PEF post-dose for the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day.
Time frame: Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing
Population: ITT population; Last Observation Carried Forward (LOCF) used for Day 22
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albuterol | Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 | Day 1 (n=52, 51) | 41.50 minutes |
| Albuterol | Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 | Day 22 with LOCF (n=52, 51) | 34.5 minutes |
| Placebo | Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 | Day 1 (n=52, 51) | 35.00 minutes |
| Placebo | Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 | Day 22 with LOCF (n=52, 51) | 63.00 minutes |
Comparison: Day 1p-value: 0.505995% CI: [0.77, 1.69]Regression, Cox
Comparison: Day 22p-value: 0.033395% CI: [1.03, 2.27]Regression, Cox
Secondary
Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3
Highest daily asthma symptom scores by study week. For this assessment, patients self-evaluate and record on the diary card the following asthma symptoms experienced during the day (i.e. last 12-14 hours): wheeze, shortness of breath, cough, tightness of chest. The worst of these symptoms were scored daily on a four-point scale: * 0 = No symptoms occurred * 1 = Symptom occurred but did not interfere with daily activity * 2 = Symptom occurred but was sometimes annoying or interfered with daily activity * 3 = Symptom present even at rest and was annoying or interfered with daily activity
Time frame: Weeks 1, 2, 3
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Week 1 (N=50, N=50) | 0.370 units on a scale | Standard Error 0.07 |
| Albuterol | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Week 2 (N=50, N=49) | 0.376 units on a scale | Standard Error 0.07 |
| Albuterol | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Week 3 (N=47, N=48) | 0.336 units on a scale | Standard Error 0.072 |
| Placebo | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Week 1 (N=50, N=50) | 0.442 units on a scale | Standard Error 0.07 |
| Placebo | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Week 2 (N=50, N=49) | 0.547 units on a scale | Standard Error 0.071 |
| Placebo | Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 | Week 3 (N=47, N=48) | 0.474 units on a scale | Standard Error 0.071 |
Comparison: Week 1p-value: 0.467495% CI: [-0.265, 0.122]ANCOVA
Comparison: Week 2p-value: 0.08495% CI: [-0.365, 0.023]ANCOVA
Comparison: Week 3p-value: 0.169995% CI: [-0.335, 0.059]ANCOVA
Secondary
Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3
Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night and the number of puffs of rescue albuterol used during the night after going to bed. At the end of each day, the number of puffs of albuterol rescue medication used during the day were recorded.
Time frame: Weeks 1, 2, 3
Population: ITT population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Albuterol | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Week 1 (N=51, N=50) | 0.074 Number of puffs per day |
| Albuterol | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Week 2 (N=51, N=49) | 0.084 Number of puffs per day |
| Albuterol | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Week 3 (N=49, N=48) | 0.078 Number of puffs per day |
| Placebo | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Week 1 (N=51, N=50) | 0.075 Number of puffs per day |
| Placebo | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Week 2 (N=51, N=49) | 0.088 Number of puffs per day |
| Placebo | Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 | Week 3 (N=49, N=48) | 0.088 Number of puffs per day |
Comparison: Week 1~P-value, mean and confidence interval calculated from a 0 inflated mixed poisson regression model with fixed effect terms for treatment, week, treatment by week interaction, baseline as a covariate and a random term for subject. The null hypothesis is that the ratio equals 1. Estimated means are conditional upon the random effect, assume a random effect of 0 and a covariate value at the average.p-value: 0.984695% CI: [-0.121, 2.099]mixed poisson regression model
Comparison: Week 2~P-value, mean and confidence interval calculated from a 0 inflated mixed poisson regression model with fixed effect terms for treatment, week, treatment by week interaction, baseline as a covariate and a random term for subject. The null hypothesis is that the ratio equals 1. Estimated means are conditional upon the random effect, assume a random effect of 0 and a covariate value at the average.p-value: 0.944795% CI: [-0.116, 2.039]mixed poisson regression model
Comparison: Week 3~P-value, mean and confidence interval calculated from a 0 inflated mixed poisson regression model with fixed effect terms for treatment, week, treatment by week interaction, baseline as a covariate and a random term for subject. The null hypothesis is that the ratio equals 1. Estimated means are conditional upon the random effect, assume a random effect of 0 and a covariate value at the average.p-value: 0.832695% CI: [-0.111, 1.885]mixed poisson regression model
Secondary
Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning
Participants measured their PEF as trained by taking as deep a breath as possible, placing their mouth firmly around the mouthpiece of the flow meter to form a tight seal, and exhaling as hard and as fast as possible. Subjects repeated the process twice at intervals of approximately 30 seconds, and then recorded the highest of the three PEF values on the diary card.
Time frame: Weeks 1, 2, 3
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Week 1 (N=51, N=50) | 229.65 Liters/minute | Standard Error 4.8 |
| Albuterol | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Week 2 (N=51, N=49) | 229.90 Liters/minute | Standard Error 4.8 |
| Albuterol | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Week 3 (N=49, N=48) | 231.28 Liters/minute | Standard Error 4.82 |
| Placebo | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Week 1 (N=51, N=50) | 219.72 Liters/minute | Standard Error 4.854 |
| Placebo | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Week 2 (N=51, N=49) | 218.97 Liters/minute | Standard Error 4.87 |
| Placebo | Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning | Week 3 (N=49, N=48) | 221.73 Liters/minute | Standard Error 4.88 |
Comparison: Week 1p-value: 0.139195% CI: [-3.256, 23.108]ANCOVA
Comparison: Week 2p-value: 0.104395% CI: [-2.278, 24.124]ANCOVA
Comparison: Week 3p-value: 0.15795% CI: [-3.705, 22.798]ANCOVA