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 African American population.
Interventions
Symbicort pMDI 160/4.5 ug x 2 actuations twice daily (BID)
Budesonide HFA pMDI 160 ug x 2 actuations BID
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, African American (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 |
|---|---|---|
| Total Number of Asthma Exacerbations | 52 Weeks | An exacerbation was defined as symptomatic worsening requiring oral/systemic glucocorticoid therapy and/or emergency room visit and/or urgent care center visit and/or hospitalization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QT Interval Corrected Using the Fridericia Formula Measured Via Electrocardiogram (ECG) | Baseline and 52 weeks | QT interval corrected using the Fridericia formula \[QTc (Frid)\] - Change from baseline to end of treatment |
| Number of Patients With Shift From Normal to High Rate of Total Ectopic Ventricular Beats as Measured by 24-hour Holter Monitor Assessment | Baseline and 2 weeks (visit 4) | Total ectopic ventricular (VE) beats - number of participants with shift from normal (\<50) to high (≥50) from baseline to visit 4. |
| Number of Patients With Shift From Normal to High Rate of Total Ectopic Supraventricular Beats as Measured by 24-hour Holter Monitor Assessment | Baseline and 2 weeks (visit 4) | Total ectopic supraventricular (VE) beats - number of participants with shift normal (\<50) to high (≥50) from baseline to visit 4. |
| Total Number of Ventricular Runs as Measured by 24-hour Holter Monitor Assessment | Baseline and 2 weeks (visit 4) | Total ventricular runs - number of participants with shift normal (\<1) to high (≥1) from baseline to week 2. |
| Diary Assessments - Rescue-free Day | baseline and 52 weeks | Calculated as the number of rescue-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % rescue-free days in the baseline period and the active treatment period. A rescue-free day was one in which the patient answered no to having used rescue medication that day |
| Asthma Exacerbations | 52 Weeks | Number of participants with at least 1 exacerbation |
| Diary Assessments - Asthma-control Day | baseline and 52 weeks | Calculated as the number of asthma control days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % asthma control days in the baseline period and the active treatment period. An asthma control day was one in which the patient answered no to having symptoms and 0 to the use of rescue medication that day |
| Onset of Effect Questionnaire (OEQ) | 1 week | Number of participants with positive response to Item 2 in questionnaire During the past week,you could feel your study medication begin to work right away. A positive response was defined as a response of strongly agree or somewhat agree |
| Peak Expiratory Flow (PEF) in Morning | baseline and 52 weeks | Change in AM PEF from baseline (mean over the 2 weeks run-in) to the average of the randomized treatment period. |
| Forced Expiratory Volume in One Second (FEV1) | baseline and 52 weeks | Change in pre-dose FEV1 from baseline (end of run-in, visit 3) to the average of the randomized treatment period |
| Asthma Treatment Satisfaction Measure (ATSM) | Baseline and 52 weeks | Overall score - change from baseline to end of treatment. For 11 individual attributes, expectations were subtracted from the outcomes. This difference and the importance rating were combined in a weighted average which was then multiplied by the raw satisfaction measure. The final derived satisfaction measure was transformed to a 0 to 100 scale, with higher scores representing greater satisfaction. |
| Diary Assessments - Symptom-free Day | baseline and 52 weeks | Calculated as the number of symptom-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % symptom-free days in the baseline period and the active treatment period. A symptom-free day was one in which the patient answered no to having symptoms that day |
Countries
United States
Participant flow
Recruitment details
First patient enrolled on 8 February 2007, the last patient completed the study on 30 November 2009. The study randomized participants only in the United States.
Pre-assignment details
The study included a run-in period of 2 weeks when all patients were prescribed budesonide HFA pMDI 160 μg times 2 actuations BID at individual daily doses and rescue medication, as needed. To be randomized to treatment the patients needed to show pre-dose FEV1 of ≥50%. One patient in the budesonide group did not receive any dose.
Participants by arm
| Arm | Count |
|---|---|
| Symbicort Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID | 377 |
| Budesonide Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID | 365 |
| Total | 742 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal ECG | 1 | 0 |
| Overall Study | Adverse Event | 8 | 10 |
| Overall Study | Diary or medication non-compliance | 2 | 4 |
| Overall Study | Incorrectly enrolled | 10 | 3 |
| Overall Study | Intake of prohibited medication | 2 | 2 |
| Overall Study | Lost to Follow-up | 43 | 34 |
| Overall Study | Occurence of 2 or more exacerbations | 2 | 0 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Pregnancy | 4 | 2 |
| Overall Study | Protocol Violation | 32 | 24 |
| Overall Study | Withdrawal by Subject | 44 | 43 |
Baseline characteristics
| Characteristic | Symbicort | Budesonide | Total |
|---|---|---|---|
| Age Continuous | 36.19 Years STANDARD_DEVIATION 15.67 | 38.35 Years STANDARD_DEVIATION 15.22 | 37.27 Years STANDARD_DEVIATION 15.48 |
| Sex: Female, Male Female | 249 Participants | 232 Participants | 481 Participants |
| Sex: Female, Male Male | 128 Participants | 133 Participants | 261 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 377 | 84 / 365 |
| serious Total, serious adverse events | 12 / 377 | 15 / 365 |
Outcome results
Primary
Total Number of Asthma Exacerbations
An exacerbation was defined as symptomatic worsening requiring oral/systemic glucocorticoid therapy and/or emergency room visit and/or urgent care center visit and/or hospitalization.
Time frame: 52 Weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Total Number of Asthma Exacerbations | 36 Exacerbations |
| Budesonide | Total Number of Asthma Exacerbations | 61 Exacerbations |
Secondary
Asthma Exacerbations
Number of participants with at least 1 exacerbation
Time frame: 52 Weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Asthma Exacerbations | 29 Participants |
| Budesonide | Asthma Exacerbations | 51 Participants |
Secondary
Asthma Treatment Satisfaction Measure (ATSM)
Overall score - change from baseline to end of treatment. For 11 individual attributes, expectations were subtracted from the outcomes. This difference and the importance rating were combined in a weighted average which was then multiplied by the raw satisfaction measure. The final derived satisfaction measure was transformed to a 0 to 100 scale, with higher scores representing greater satisfaction.
Time frame: Baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | Asthma Treatment Satisfaction Measure (ATSM) | 47.99 units on a scale |
| Budesonide | Asthma Treatment Satisfaction Measure (ATSM) | 45.64 units on a scale |
Secondary
Diary Assessments - Asthma-control Day
Calculated as the number of asthma control days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % asthma control days in the baseline period and the active treatment period. An asthma control day was one in which the patient answered no to having symptoms and 0 to the use of rescue medication that day
Time frame: baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | Diary Assessments - Asthma-control Day | 16.68 percentage of Asthma-control day |
| Budesonide | Diary Assessments - Asthma-control Day | 11.62 percentage of Asthma-control day |
Secondary
Diary Assessments - Rescue-free Day
Calculated as the number of rescue-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % rescue-free days in the baseline period and the active treatment period. A rescue-free day was one in which the patient answered no to having used rescue medication that day
Time frame: baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | Diary Assessments - Rescue-free Day | 15.88 Percentage of Rescue Free Day |
| Budesonide | Diary Assessments - Rescue-free Day | 10.62 Percentage of Rescue Free Day |
Secondary
Diary Assessments - Symptom-free Day
Calculated as the number of symptom-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % symptom-free days in the baseline period and the active treatment period. A symptom-free day was one in which the patient answered no to having symptoms that day
Time frame: baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | Diary Assessments - Symptom-free Day | 9.46 percentage of Symptom-free day |
| Budesonide | Diary Assessments - Symptom-free Day | 7.58 percentage of Symptom-free day |
Secondary
Forced Expiratory Volume in One Second (FEV1)
Change in pre-dose FEV1 from baseline (end of run-in, visit 3) to the average of the randomized treatment period
Time frame: baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | Forced Expiratory Volume in One Second (FEV1) | 0.08 Litres |
| Budesonide | Forced Expiratory Volume in One Second (FEV1) | -0.01 Litres |
Secondary
Number of Patients With Shift From Normal to High Rate of Total Ectopic Supraventricular Beats as Measured by 24-hour Holter Monitor Assessment
Total ectopic supraventricular (VE) beats - number of participants with shift normal (\<50) to high (≥50) from baseline to visit 4.
Time frame: Baseline and 2 weeks (visit 4)
Population: Data were available for a subset of patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Number of Patients With Shift From Normal to High Rate of Total Ectopic Supraventricular Beats as Measured by 24-hour Holter Monitor Assessment | 4 Participants |
| Budesonide | Number of Patients With Shift From Normal to High Rate of Total Ectopic Supraventricular Beats as Measured by 24-hour Holter Monitor Assessment | 3 Participants |
Secondary
Number of Patients With Shift From Normal to High Rate of Total Ectopic Ventricular Beats as Measured by 24-hour Holter Monitor Assessment
Total ectopic ventricular (VE) beats - number of participants with shift from normal (\<50) to high (≥50) from baseline to visit 4.
Time frame: Baseline and 2 weeks (visit 4)
Population: Data were available for a subset of patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Number of Patients With Shift From Normal to High Rate of Total Ectopic Ventricular Beats as Measured by 24-hour Holter Monitor Assessment | 4 Participants |
| Budesonide | Number of Patients With Shift From Normal to High Rate of Total Ectopic Ventricular Beats as Measured by 24-hour Holter Monitor Assessment | 3 Participants |
Secondary
Onset of Effect Questionnaire (OEQ)
Number of participants with positive response to Item 5 in questionnaire During the past week, you were satisfied with how quickly you felt your study medication begin to work. The scale was scored on a 5-point Likert scale from strongly agree to strongly disagree. A positive response was defined as a response of strongly agree or somewhat agree
Time frame: 1 week
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Onset of Effect Questionnaire (OEQ) | 165 Participants |
| Budesonide | Onset of Effect Questionnaire (OEQ) | 157 Participants |
Secondary
Onset of Effect Questionnaire (OEQ)
Number of participants with positive response to Item 2 in questionnaire During the past week,you could feel your study medication begin to work right away. A positive response was defined as a response of strongly agree or somewhat agree
Time frame: 1 week
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Onset of Effect Questionnaire (OEQ) | 172 Participants |
| Budesonide | Onset of Effect Questionnaire (OEQ) | 158 Participants |
Secondary
Peak Expiratory Flow (PEF) in Morning
Change in AM PEF from baseline (mean over the 2 weeks run-in) to the average of the randomized treatment period.
Time frame: baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | Peak Expiratory Flow (PEF) in Morning | 30.13 Liters/minute |
| Budesonide | Peak Expiratory Flow (PEF) in Morning | 19.73 Liters/minute |
Secondary
QT Interval Corrected Using the Fridericia Formula Measured Via Electrocardiogram (ECG)
QT interval corrected using the Fridericia formula \[QTc (Frid)\] - Change from baseline to end of treatment
Time frame: Baseline and 52 weeks
Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort | QT Interval Corrected Using the Fridericia Formula Measured Via Electrocardiogram (ECG) | -0.11 msec |
| Budesonide | QT Interval Corrected Using the Fridericia Formula Measured Via Electrocardiogram (ECG) | -0.31 msec |
Secondary
Total Number of Ventricular Runs as Measured by 24-hour Holter Monitor Assessment
Total ventricular runs - number of participants with shift normal (\<1) to high (≥1) from baseline to week 2.
Time frame: Baseline and 2 weeks (visit 4)
Population: Data were available for a subset of patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort | Total Number of Ventricular Runs as Measured by 24-hour Holter Monitor Assessment | 2 Participants |
| Budesonide | Total Number of Ventricular Runs as Measured by 24-hour Holter Monitor Assessment | 1 Participants |