Asthma
Conditions
Keywords
Moderate asthma, Severe asthma
Brief summary
The purpose of this study is to determine the effectiveness and safety of SYMBICORT® pMDI (a medication approved by the Food and Drug Administration(FDA)) in the Hispanic population.
Interventions
SYMBICORT® pMDI 160/4.5 μg x 2 actuations twice daily
Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations 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
* Male or Female, Hispanic (self-reported), \> 12 years of age * Moderate to severe asthma requiring treatment with an inhaled corticosteroid * Diagnosis of asthma for at least 6 months
Exclusion criteria
* Subjects requiring treatment with systemic corticosteroids (e.g., oral, parenteral, ocular) * Any significant disease or disorder that may jeopardize a subject's safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morning Peak Expiratory Flow (AM PEF) | Baseline (run-in) and throughout 12 weeks | Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks, with baseline value as covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pre-defined Asthma Events | 12 weeks | Asthma Events, defined as any of: decrease in lung function (FEV1 or AM PEF), use of rescue medication over maximum allowed per day, night awakening requiring use of rescue medication, exacerbation of asthma requiring medical assistance, use of not allowed asthma medication |
| Percentage of Participants With Withdrawals Due to Pre-defined Asthma Events | 12 weeks | Percentage of participants with Withdrawals Due to Pre-defined Asthma Events as recorded in CRF. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. |
| Changes Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | Baseline, 2, 6 and 12 weeks | Changes in pre-dose FEV1 from baseline to the average value over the treatment period, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. |
| Change From Baseline in a Evening Peak Expiratory Flow (PM PEF) | Baseline (run-in) and throughout 12 weeks | Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks with baseline as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. |
| Change in Nighttime Asthma Symptom Score From Baseline Through 12 Weeks | Baseline (run-in) and throughout 12 weeks | Change from baseline in average of daily scores for nighttime asthma over 12 weeks of treatment, with baseline value as covariate. Daily scale: * 0 = No symptoms * 1 = Mild symptoms * 2 = Moderate symptoms * 3 = Severe symptoms |
| Change in Daytime Asthma Symptom Score From Baseline Through 12 Weeks | Baseline (run-in) and throughout 12 weeks | Change from baseline in average of daily scores for daytime asthma over 12 weeks of treatment, with baseline value as covariate. Daily scale: * 0 = No symptoms * 1 = Mild symptoms * 2 = Moderate symptoms * 3 = Severe symptoms |
| Change in Asthma Related Awakenings Free Nights, From Baseline Through 12 Weeks | Baseline (run-in) and throughout 12 weeks | Change from baseline in percentage of nights with awakenings due to asthma over 12 weeks of treatment, with baseline value as covariate. |
| Change From Baseline in Rescue Medication Use Over 12 Weeks of Treatment | Baseline (run-in) and throughout 12 weeks | Change from baseline in rescue medication use over 12 weeks of treatment with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. |
| Change From Baseline in Rescue-free Days Over 12 Weeks of Treatment | Baseline (run-in) and throughout 12 weeks | Change from baseline in percentage of rescue-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. |
| Subject Global Assessment | Baseline and week 12 | The assessment was made using a 5-point Likert scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1 and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses. |
| Change From Baseline in Symptom-free Days Over 12 Weeks of Treatment | Baseline (run-in) and throughout 12 weeks | Change from baseline in percentage of symptom-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. |
| Physician Global Assessment | Baseline and week 12 | The assessment was made using a 5-point scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses. |
| Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Control Relief Index | Week 12 | Mean scores (6-points scale, where 1-means the most positive opinion and 6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. |
| Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Overall Perception of Medication | Week 12 | Mean scores (6 or 5-points scale, where 1-means the most positive opinion and 5/6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. |
| Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Comparison With Other Medications | Week 12 | Mean scores (5-points scale, where 1-means the most positive opinion and 5-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
39 centres in United States enrolled 558 patients with asthma into this study. 308 patients were excluded: 279 for incorrect enrollment/eligibility criteria not fulfilled, 14 for voluntary discontinuations, 2 for development of study specific discontinuation criteria, 2 for adverse events, 10 were lost to follow-up
Pre-assignment details
Male or female, Hispanic (self-reported), ≥12 years
Participants by arm
| Arm | Count |
|---|---|
| Symbicort SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily | 127 |
| Budesonide Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily | 123 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Multiple reasons | 3 | 1 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Study specific discontinuation criteria | 4 | 8 |
| Overall Study | Withdrawal by Subject | 7 | 1 |
Baseline characteristics
| Characteristic | Symbicort | Budesonide | Total |
|---|---|---|---|
| Age Continuous | 16.6 Years STANDARD_DEVIATION 39.8 | 14.9 Years STANDARD_DEVIATION 37 | 15.6 Years STANDARD_DEVIATION 38.4 |
| Sex: Female, Male Female | 84 Participants | 80 Participants | 164 Participants |
| Sex: Female, Male Male | 43 Participants | 43 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 127 | 48 / 123 |
| serious Total, serious adverse events | 4 / 127 | 0 / 123 |
Outcome results
Primary
Morning Peak Expiratory Flow (AM PEF)
Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks, with baseline value as covariate.
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Morning Peak Expiratory Flow (AM PEF) | 25.40 Liters/minutes | Standard Error 6 |
| Budesonide | Morning Peak Expiratory Flow (AM PEF) | 19.90 Liters/minutes | Standard Error 6.5 |
Secondary
Change From Baseline in a Evening Peak Expiratory Flow (PM PEF)
Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks with baseline as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change From Baseline in a Evening Peak Expiratory Flow (PM PEF) | 20.60 Liters/minutes | Standard Error 6.2 |
| Budesonide | Change From Baseline in a Evening Peak Expiratory Flow (PM PEF) | 15.80 Liters/minutes | Standard Error 6.7 |
Secondary
Change From Baseline in Rescue-free Days Over 12 Weeks of Treatment
Change from baseline in percentage of rescue-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change From Baseline in Rescue-free Days Over 12 Weeks of Treatment | 19.70 Percentage of days | Standard Error 3.3 |
| Budesonide | Change From Baseline in Rescue-free Days Over 12 Weeks of Treatment | 17.70 Percentage of days | Standard Error 3.5 |
Secondary
Change From Baseline in Rescue Medication Use Over 12 Weeks of Treatment
Change from baseline in rescue medication use over 12 weeks of treatment with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change From Baseline in Rescue Medication Use Over 12 Weeks of Treatment | -0.80 puffs/day | Standard Error 0.2 |
| Budesonide | Change From Baseline in Rescue Medication Use Over 12 Weeks of Treatment | -0.60 puffs/day | Standard Error 0.2 |
Secondary
Change From Baseline in Symptom-free Days Over 12 Weeks of Treatment
Change from baseline in percentage of symptom-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change From Baseline in Symptom-free Days Over 12 Weeks of Treatment | 24.40 Percentage of days | Standard Error 3.3 |
| Budesonide | Change From Baseline in Symptom-free Days Over 12 Weeks of Treatment | 21.00 Percentage of days | Standard Error 3.5 |
Secondary
Change in Asthma Related Awakenings Free Nights, From Baseline Through 12 Weeks
Change from baseline in percentage of nights with awakenings due to asthma over 12 weeks of treatment, with baseline value as covariate.
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change in Asthma Related Awakenings Free Nights, From Baseline Through 12 Weeks | 5.40 Percentage of nights | Standard Error 1.7 |
| Budesonide | Change in Asthma Related Awakenings Free Nights, From Baseline Through 12 Weeks | 5.50 Percentage of nights | Standard Error 1.9 |
Secondary
Change in Daytime Asthma Symptom Score From Baseline Through 12 Weeks
Change from baseline in average of daily scores for daytime asthma over 12 weeks of treatment, with baseline value as covariate. Daily scale: * 0 = No symptoms * 1 = Mild symptoms * 2 = Moderate symptoms * 3 = Severe symptoms
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change in Daytime Asthma Symptom Score From Baseline Through 12 Weeks | -0.40 Units on a scale | Standard Error 0.01 |
| Budesonide | Change in Daytime Asthma Symptom Score From Baseline Through 12 Weeks | -0.30 Units on a scale | Standard Error 0.01 |
Secondary
Change in Nighttime Asthma Symptom Score From Baseline Through 12 Weeks
Change from baseline in average of daily scores for nighttime asthma over 12 weeks of treatment, with baseline value as covariate. Daily scale: * 0 = No symptoms * 1 = Mild symptoms * 2 = Moderate symptoms * 3 = Severe symptoms
Time frame: Baseline (run-in) and throughout 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Change in Nighttime Asthma Symptom Score From Baseline Through 12 Weeks | -0.40 Units on a scale | Standard Error 0.01 |
| Budesonide | Change in Nighttime Asthma Symptom Score From Baseline Through 12 Weeks | -0.30 Units on a scale | Standard Error 0.01 |
Secondary
Changes Pre-dose Forced Expiratory Volume in 1 Second (FEV1)
Changes in pre-dose FEV1 from baseline to the average value over the treatment period, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
Time frame: Baseline, 2, 6 and 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Changes Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.16 Liters | Standard Error 0.03 |
| Budesonide | Changes Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.11 Liters | Standard Error 0.03 |
Secondary
Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Comparison With Other Medications
Mean scores (5-points scale, where 1-means the most positive opinion and 5-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction.
Time frame: Week 12
Population: Only subjects 18 years and older, who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Comparison With Other Medications | 88.45 Units on a scale | Standard Error 2.34 |
| Budesonide | Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Comparison With Other Medications | 80.60 Units on a scale | Standard Error 2.47 |
Secondary
Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Control Relief Index
Mean scores (6-points scale, where 1-means the most positive opinion and 6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction.
Time frame: Week 12
Population: Only subjects 18 years and older, who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Control Relief Index | 87.20 Units on a scale | Standard Error 1.97 |
| Budesonide | Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Control Relief Index | 82.50 Units on a scale | Standard Error 2.08 |
Secondary
Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Overall Perception of Medication
Mean scores (6 or 5-points scale, where 1-means the most positive opinion and 5/6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction.
Time frame: Week 12
Population: Only subjects 18 years and older, who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Symbicort | Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Overall Perception of Medication | 90.67 Units on a scale | Standard Error 1.79 |
| Budesonide | Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Overall Perception of Medication | 86.66 Units on a scale | Standard Error 1.89 |
Secondary
Percentage of Participants With Pre-defined Asthma Events
Asthma Events, defined as any of: decrease in lung function (FEV1 or AM PEF), use of rescue medication over maximum allowed per day, night awakening requiring use of rescue medication, exacerbation of asthma requiring medical assistance, use of not allowed asthma medication
Time frame: 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Percentage of Participants With Pre-defined Asthma Events | 25.20 Percentage of Participants |
| Budesonide | Percentage of Participants With Pre-defined Asthma Events | 31.70 Percentage of Participants |
Secondary
Percentage of Participants With Withdrawals Due to Pre-defined Asthma Events
Percentage of participants with Withdrawals Due to Pre-defined Asthma Events as recorded in CRF. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
Time frame: 12 weeks
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Percentage of Participants With Withdrawals Due to Pre-defined Asthma Events | 2.10 Percentage of Participants |
| Budesonide | Percentage of Participants With Withdrawals Due to Pre-defined Asthma Events | 6.50 Percentage of Participants |
Secondary
Physician Global Assessment
The assessment was made using a 5-point scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses.
Time frame: Baseline and week 12
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Physician Global Assessment | 92.00 Perscentage of Participants |
| Budesonide | Physician Global Assessment | 84.60 Perscentage of Participants |
Secondary
Subject Global Assessment
The assessment was made using a 5-point Likert scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1 and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses.
Time frame: Baseline and week 12
Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Subject Global Assessment | 88.70 Percent of Participants |
| Budesonide | Subject Global Assessment | 86.30 Percent of Participants |