Bronchial Asthma
Conditions
Keywords
Asthma, Symbicort
Brief summary
The purpose of the this study is to evaluate the efficacy and safety of 2 actuations Symbicort®pMDI® 40/2.25 μg twice daily compared with1 inhalation Symbicort Turbuhaler® 80/4.5 μg twice daily and 1 inhalation Pulmicort®Turbuhaler® 100 μg twice daily for 6 weeks.
Interventions
Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily
DRUGSymbicort pMDI
Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily
Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Asthma clinically diagnosed since at least 6 months. * Lung function values measured ≥ 50% and ≤ 90% of predicted normal. * Patients with reversible airway obstruction Daily use of inhaled steroids (any brand) for \>3 months.
Exclusion criteria
* Use of oral, rectal or parenteral steroids within 30 days prior to start of study. * Respiratory infection affecting the asthma, as judged by the investigator, within 30 days prior to start of randomised treatment. * Any significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study or the patient's ability to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morning Peak Expiratory Flow (PEF) | Baseline to 6 weeks | Change in the Morning PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Symptom Score, Night | Baseline to 6 weeks | Change in the Asthma Symptom Score (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. |
| Asthma Symptom Score, Day | Baseline to 6 weeks | Change in the Asthma Symptom Score (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. |
| Asthma Symptom Score, Total | Baseline to 6 weeks | Change in the Asthma Symptom Score (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. |
| Percentage of Nights With Awakenings Due to Asthma | Baseline and 6 weeks | Change in the Percentage of Nights With Awakenings Due to Asthma from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. The participants answered Yes or No whether she/he woke up during the night due to asthma. |
| Use of Rescue Medication, Night | Baseline to 6 weeks | Change in the Use of Rescue Medication (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed |
| Evening Peak Expiratory Flow (PEF) | Baseline to 6 weeks | Change in the Evening PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed |
| Use of Rescue Medication, Total | Baseline to 6 weeks | Change in the Use of Rescue Medication (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed |
| Percentage of Symptom-free Days | Baseline to 6 weeks | Change in the Percentage of Symptom-free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Symptom-free Day: no symptoms (asthma symptom score=0) night and day, and no awakenings due to asthma. |
| Percentage of Asthma Control Days | Baseline to 6 weeks | Change in the Percentage of Symptom Control Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Asthma Control Day: no symptoms (asthma symptom score=0) night and day, no awakenings due to asthma, no rescue medication. |
| Percentage of Rescue Free Days | Baseline to 6 weeks | Change in the Percentage of Rescue Free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Rescue-free Day defined as day and night with no use of rescue medication. |
| Forced Expiratory Volume in 1 Second (FEV1) | Baseline to 6 weeks | Change in the FEV1from baseline to week 6 (calculated as a mean using all available data after randomization) |
| Use of Rescue Medication, Day | Baseline to 6 weeks | Change in the Use of Rescue Medication (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed |
Countries
Bulgaria, Czechia, Hungary, Poland
Participant flow
Recruitment details
898 subjects enrolled; 156 not randomised: 94 incorrect enrolment, 9 adverse events, 18 voluntary discontinuations, 1 lost to follow-up, 1use of not allowed medication, 1 non-compliant
Participants by arm
| Arm | Count |
|---|---|
| Symbicort pMDI Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily | 253 |
| Symbicort Turbuhaler Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily | 246 |
| Pulmicort Turbuhaler Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily | 243 |
| Total | 742 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 3 |
| Overall Study | Intake of prohibited conc. medication | 0 | 0 | 1 |
| Overall Study | Other | 1 | 1 | 0 |
| Overall Study | Safety reasons | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Symbicort pMDI | Symbicort Turbuhaler | Pulmicort Turbuhaler | Total |
|---|---|---|---|---|
| Age Continuous | 41 years | 42 years | 39 years | 41 years |
| Sex: Female, Male Female | 152 Participants | 142 Participants | 131 Participants | 425 Participants |
| Sex: Female, Male Male | 101 Participants | 104 Participants | 112 Participants | 317 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 253 | 0 / 246 | 0 / 243 |
| serious Total, serious adverse events | 0 / 253 | 1 / 246 | 1 / 243 |
Outcome results
Primary
Morning Peak Expiratory Flow (PEF)
Change in the Morning PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Morning Peak Expiratory Flow (PEF) | 12.88 Liters/min | Standard Deviation 24.6 |
| Symbicort Turbuhaler | Morning Peak Expiratory Flow (PEF) | 13.78 Liters/min | Standard Deviation 29.7 |
| Pulmicort Turbuhaler | Morning Peak Expiratory Flow (PEF) | 4.59 Liters/min | Standard Deviation 27.9 |
Secondary
Asthma Symptom Score, Day
Change in the Asthma Symptom Score (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms.
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Asthma Symptom Score, Day | -0.21 Units on a scale | Standard Deviation 0.38 |
| Symbicort Turbuhaler | Asthma Symptom Score, Day | -0.24 Units on a scale | Standard Deviation 0.4 |
| Pulmicort Turbuhaler | Asthma Symptom Score, Day | -0.15 Units on a scale | Standard Deviation 0.4 |
Secondary
Asthma Symptom Score, Night
Change in the Asthma Symptom Score (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms.
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Asthma Symptom Score, Night | -0.24 Units on a scale | Standard Deviation 0.41 |
| Symbicort Turbuhaler | Asthma Symptom Score, Night | -0.27 Units on a scale | Standard Deviation 0.41 |
| Pulmicort Turbuhaler | Asthma Symptom Score, Night | -0.15 Units on a scale | Standard Deviation 0.39 |
Secondary
Asthma Symptom Score, Total
Change in the Asthma Symptom Score (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms.
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Asthma Symptom Score, Total | -0.45 Units on a scale | Standard Deviation 0.73 |
| Symbicort Turbuhaler | Asthma Symptom Score, Total | -0.51 Units on a scale | Standard Deviation 0.75 |
| Pulmicort Turbuhaler | Asthma Symptom Score, Total | -0.30 Units on a scale | Standard Deviation 0.73 |
Secondary
Evening Peak Expiratory Flow (PEF)
Change in the Evening PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Evening Peak Expiratory Flow (PEF) | 12.34 Liters/min | Standard Deviation 24.3 |
| Symbicort Turbuhaler | Evening Peak Expiratory Flow (PEF) | 10.80 Liters/min | Standard Deviation 29.1 |
| Pulmicort Turbuhaler | Evening Peak Expiratory Flow (PEF) | 1.43 Liters/min | Standard Deviation 25.7 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1)
Change in the FEV1from baseline to week 6 (calculated as a mean using all available data after randomization)
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Forced Expiratory Volume in 1 Second (FEV1) | 0.095 Liters | Standard Deviation 0.328 |
| Symbicort Turbuhaler | Forced Expiratory Volume in 1 Second (FEV1) | 0.147 Liters | Standard Deviation 0.364 |
| Pulmicort Turbuhaler | Forced Expiratory Volume in 1 Second (FEV1) | 0.112 Liters | Standard Deviation 0.326 |
Secondary
Percentage of Asthma Control Days
Change in the Percentage of Symptom Control Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Asthma Control Day: no symptoms (asthma symptom score=0) night and day, no awakenings due to asthma, no rescue medication.
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Percentage of Asthma Control Days | 12.7 Percentage of days | Standard Deviation 23.6 |
| Symbicort Turbuhaler | Percentage of Asthma Control Days | 15.1 Percentage of days | Standard Deviation 24.4 |
| Pulmicort Turbuhaler | Percentage of Asthma Control Days | 9.1 Percentage of days | Standard Deviation 21.2 |
Secondary
Percentage of Nights With Awakenings Due to Asthma
Change in the Percentage of Nights With Awakenings Due to Asthma from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. The participants answered Yes or No whether she/he woke up during the night due to asthma.
Time frame: Baseline and 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Percentage of Nights With Awakenings Due to Asthma | -14.0 Percentage of night | Standard Deviation 24.1 |
| Symbicort Turbuhaler | Percentage of Nights With Awakenings Due to Asthma | -14.0 Percentage of night | Standard Deviation 26.4 |
| Pulmicort Turbuhaler | Percentage of Nights With Awakenings Due to Asthma | -8.3 Percentage of night | Standard Deviation 25.5 |
Secondary
Percentage of Rescue Free Days
Change in the Percentage of Rescue Free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Rescue-free Day defined as day and night with no use of rescue medication.
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Percentage of Rescue Free Days | 24.0 Percentage of days | Standard Deviation 30.9 |
| Symbicort Turbuhaler | Percentage of Rescue Free Days | 26.2 Percentage of days | Standard Deviation 30.7 |
| Pulmicort Turbuhaler | Percentage of Rescue Free Days | 17.2 Percentage of days | Standard Deviation 28.4 |
Secondary
Percentage of Symptom-free Days
Change in the Percentage of Symptom-free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Symptom-free Day: no symptoms (asthma symptom score=0) night and day, and no awakenings due to asthma.
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Percentage of Symptom-free Days | 12.5 Percentage of days | Standard Deviation 23.7 |
| Symbicort Turbuhaler | Percentage of Symptom-free Days | 15.3 Percentage of days | Standard Deviation 24.5 |
| Pulmicort Turbuhaler | Percentage of Symptom-free Days | 9.1 Percentage of days | Standard Deviation 21.2 |
Secondary
Use of Rescue Medication, Day
Change in the Use of Rescue Medication (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Use of Rescue Medication, Day | -0.21 Inhalations | Standard Deviation 0.39 |
| Symbicort Turbuhaler | Use of Rescue Medication, Day | -0.20 Inhalations | Standard Deviation 0.47 |
| Pulmicort Turbuhaler | Use of Rescue Medication, Day | -0.13 Inhalations | Standard Deviation 0.56 |
Secondary
Use of Rescue Medication, Night
Change in the Use of Rescue Medication (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Use of Rescue Medication, Night | -0.41 Inhalations | Standard Deviation 0.64 |
| Symbicort Turbuhaler | Use of Rescue Medication, Night | -0.39 Inhalations | Standard Deviation 0.76 |
| Pulmicort Turbuhaler | Use of Rescue Medication, Night | -0.19 Inhalations | Standard Deviation 0.67 |
Secondary
Use of Rescue Medication, Total
Change in the Use of Rescue Medication (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed
Time frame: Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort pMDI | Use of Rescue Medication, Total | -0.62 Inhalations | Standard Deviation 0.89 |
| Symbicort Turbuhaler | Use of Rescue Medication, Total | -0.58 Inhalations | Standard Deviation 1.09 |
| Pulmicort Turbuhaler | Use of Rescue Medication, Total | -0.32 Inhalations | Standard Deviation 1.12 |