Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Severe chronic obstructive pulmonary disease (COPD) patients
Brief summary
Efficacy and tolerability study in severe chronic obstructive pulmonary disease (COPD) patients.
Detailed description
Efficacy and tolerability study of Symbicort Turbuhaler (160/4.5µg/inhalation,2inhalations twice daily) added to Atrovent (20µg/inhalation, 2 inhalations 4 times daily) + theophylline SR(0.1g/tablet, 1 tablet p.o. twice daily) compared with Atrovent + theophylline SR in severe COPD patients.
Interventions
DRUGDrug: Budesonide/formoterol (Symbicort Turbuhaler
budesonide/formoterol (Symbicort Turbuhaler 160/4.5µg/inhalation, 2 inhalations twice daily)
DRUGDrug: ipratropium (AtroventTM)
ipratropium (AtroventTM 20 µg/inhalation, 2 inhalations four times daily)
DRUGtheophylline SR
theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent * Men or women patients ≥ 40 years of age * Diagnosis of COPD with symptoms for more than 2 years and there is a history of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1-12 months before Visit 2 * Forced Expiratory Volume in 1 second (FEV1) ≤50% of predicted normal value, pre-bronchodilator and Forced Expiratory Volume in 1 second (FEV1) / Forced Vital Capacity (FVC) \< 70%, pre-bronchodilator * Total symptom score of 2 or more per day for at least half of run-in period (breathing, cough and sputum scores from the diary card) and complete morning recordings of Digital Peak Flow Meter data at least 7 out of the last 10 days of the run-in period
Exclusion criteria
* A history of asthma and seasonal allergic rhinitis before 40 years of age * Patients who have experienced exacerbation of COPD requiring hospitalisation and /or emergency room treatment and/or a course of oral steroids and/or intravenous corticosteroids and/or antibiotics within 4 weeks prior to Visit 2 and/or during run-in period * Patients with relevant cardiovascular disorder judged by the investigator * Patients with glaucoma, prostatic hyperplasia or bladder-neck obstruction judged by the investigator * Women who are pregnant, breast-feeding or of child-bearing potential judged by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-dose FEV1 | Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug | Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-dose FEV1 at 60 Minutes | Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | Ratio of post-dose FEV1 at 60 minutes to baseline value |
| Pre-dose FVC | Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | Ratio of pre-dose FVC (Forced Vital Capacity) to baseline |
| Post-dose FVC at 5 Minutes | Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12) | Ratio of post-dose FVC at 5 minutes to baseline |
| Post-dose FVC at 60 Minutes | Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | Ratio of post-dose FVC at 60 minutes to baseline |
| Pre-dose IC | Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | Ratio of pre-dose IC (Inspiratory Capacity) to baseline |
| Post-dose IC at 60 Minutes | Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12) | Ratio of post-dose IC at 60 minutes to baseline |
| Pre-dose PEF in Last Week of Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment | Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment |
| Pre-dose PEF in First Week of Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured before inhalation of study drug in the first week of treatment | Change in pre-dose morning PEF from run-in period to first week of treatment |
| Pre-dose PEF in Whole Treatment Period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period (12 weeks) | Change in pre-dose morning PEF from run-in period to whole treatment period |
| Post-dose PEF in Last Week of Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment | Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment |
| Post-dose PEF in First Week of Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured at 5 minutes after inhalation of study drug in the first week of treatment | Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment |
| Post-dose FEV1 at 5 Minutes | Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug | Ratio of post-dose FEV1 at 5 minutes to baseline value |
| Use of Reliever Medication During Day in the Last Week on Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment | Change in the number of inhalations of reliever medication during day from run-in to the last week on treatment |
| Use of Reliever Medication During Day in the First Week on Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment | Change in the number of inhalations of reliever medication during day from run-in to the first week on treatment |
| Use of Reliever Medication During Day in the Whole Treatment Period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period (12 weeks) | Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period |
| Change in COPD Symptoms - Breathing | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks) | Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period |
| COPD Symptoms - Cough | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks) | Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period |
| COPD Symptoms Sputum | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks) | Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period |
| COPD Exacerbations | Whole treatment period (12 weeks) | Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms |
| Use of Reliever Medication During Night in the Last Week on Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the last week on treatment | Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period |
| Use of Reliever Medication During Night in the First Week on Treatment | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment | change in the number of inhalations of reliever medication during day from run-in to the first week on treatment |
| Use of Reliever Medication During Night in the Whole Treatment Period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the whole treatment period (12 weeks) | Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period |
| Post-dose PEF in Whole Treatment Period | Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period (12 weeks) | Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily) | 290 |
| Ipratropium + Theophylline SR ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily) | 292 |
| Total | 582 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Condition under Investigation Worsened | 1 | 1 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 12 |
Baseline characteristics
| Characteristic | Symbicort Turbuhaler + Ipratropium + Theophylline SR | Ipratropium + Theophylline SR | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 8.79 | 64.4 years STANDARD_DEVIATION 8.76 | 64.1 years STANDARD_DEVIATION 8.77 |
| Sex: Female, Male Female | 36 Participants | 43 Participants | 79 Participants |
| Sex: Female, Male Male | 254 Participants | 249 Participants | 503 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 293 | 31 / 289 |
| serious Total, serious adverse events | 9 / 293 | 10 / 289 |
Outcome results
Primary
Pre-dose FEV1
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value
Time frame: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Population: FAS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Pre-dose FEV1 | 1.079 Ratio |
| Ipratropium + Theophylline SR | Pre-dose FEV1 | 1.009 Ratio |
p-value: <0.000195% CI: [1.043, 1.096]ANCOVA
Secondary
Change in COPD Symptoms - Breathing
Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Change in COPD Symptoms - Breathing | -0.507 Score from 0 to 4 |
| Ipratropium + Theophylline SR | Change in COPD Symptoms - Breathing | -0.229 Score from 0 to 4 |
p-value: <0.000195% CI: [-0.381, -0.177]ANCOVA
Secondary
COPD Exacerbations
Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms
Time frame: Whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | COPD Exacerbations | 0.069 exacerbations/12 weeks |
| Ipratropium + Theophylline SR | COPD Exacerbations | 0.121 exacerbations/12 weeks |
p-value: 0.042595% CI: [0.325, 0.981]Poisson regression
p-value: 0.08895% CI: [0.339, 1.078]Regression, Cox
p-value: 0.0845Log Rank
Secondary
COPD Symptoms - Cough
Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | COPD Symptoms - Cough | -0.441 Score from 0 to 4 |
| Ipratropium + Theophylline SR | COPD Symptoms - Cough | -0.248 Score from 0 to 4 |
p-value: 0.000295% CI: [-0.294, -0.092]ANCOVA
Secondary
COPD Symptoms Sputum
Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | COPD Symptoms Sputum | -0.332 Score from 0 to 4 |
| Ipratropium + Theophylline SR | COPD Symptoms Sputum | -0.124 Score from 0 to 4 |
p-value: 0.000195% CI: [-0.308, -0.108]ANCOVA
Secondary
Post-dose FEV1 at 5 Minutes
Ratio of post-dose FEV1 at 5 minutes to baseline value
Time frame: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
Population: FAS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose FEV1 at 5 Minutes | 1.179 Ratio |
| Ipratropium + Theophylline SR | Post-dose FEV1 at 5 Minutes | 1.106 Ratio |
p-value: <0.000195% CI: [1.044, 1.09]ANCOVA
Secondary
Post-dose FEV1 at 60 Minutes
Ratio of post-dose FEV1 at 60 minutes to baseline value
Time frame: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
Population: FAS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose FEV1 at 60 Minutes | 1.219 Ratio |
| Ipratropium + Theophylline SR | Post-dose FEV1 at 60 Minutes | 1.142 Ratio |
p-value: <0.000195% CI: [1.043, 1.092]ANCOVA
Secondary
Post-dose FVC at 5 Minutes
Ratio of post-dose FVC at 5 minutes to baseline
Time frame: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose FVC at 5 Minutes | 1.170 Ratio |
| Ipratropium + Theophylline SR | Post-dose FVC at 5 Minutes | 1.120 Ratio |
p-value: <0.000195% CI: [1.024, 1.065]ANCOVA
Secondary
Post-dose FVC at 60 Minutes
Ratio of post-dose FVC at 60 minutes to baseline
Time frame: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose FVC at 60 Minutes | 1.192 Ratio |
| Ipratropium + Theophylline SR | Post-dose FVC at 60 Minutes | 1.148 Ratio |
p-value: 0.000395% CI: [1.017, 1.06]ANCOVA
Secondary
Post-dose IC at 60 Minutes
Ratio of post-dose IC at 60 minutes to baseline
Time frame: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose IC at 60 Minutes | 1.163 Ratio |
| Ipratropium + Theophylline SR | Post-dose IC at 60 Minutes | 1.120 Ratio |
p-value: 0.007495% CI: [1.01, 1.067]ANCOVA
Secondary
Post-dose PEF in First Week of Treatment
Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured at 5 minutes after inhalation of study drug in the first week of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose PEF in First Week of Treatment | 25.993 L/min |
| Ipratropium + Theophylline SR | Post-dose PEF in First Week of Treatment | 1.670 L/min |
p-value: <0.000195% CI: [14.425, 34.22]ANCOVA
Secondary
Post-dose PEF in Last Week of Treatment
Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose PEF in Last Week of Treatment | 36.612 L/min |
| Ipratropium + Theophylline SR | Post-dose PEF in Last Week of Treatment | 5.100 L/min |
p-value: <0.000195% CI: [18.74, 44.286]ANCOVA
Secondary
Post-dose PEF in Whole Treatment Period
Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Post-dose PEF in Whole Treatment Period | 26.507 L/min |
| Ipratropium + Theophylline SR | Post-dose PEF in Whole Treatment Period | -0.662 L/min |
p-value: <0.000195% CI: [18.906, 35.431]ANCOVA
Secondary
Pre-dose FVC
Ratio of pre-dose FVC (Forced Vital Capacity) to baseline
Time frame: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Pre-dose FVC | 1.072 Ratio |
| Ipratropium + Theophylline SR | Pre-dose FVC | 1.030 Ratio |
p-value: 0.000795% CI: [1.017, 1.064]ANCOVA
Secondary
Pre-dose IC
Ratio of pre-dose IC (Inspiratory Capacity) to baseline
Time frame: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Pre-dose IC | 1.068 Ratio |
| Ipratropium + Theophylline SR | Pre-dose IC | 1.032 Ratio |
p-value: 0.024895% CI: [1.004, 1.066]ANCOVA
Secondary
Pre-dose PEF in First Week of Treatment
Change in pre-dose morning PEF from run-in period to first week of treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured before inhalation of study drug in the first week of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Pre-dose PEF in First Week of Treatment | 24.393 L/min |
| Ipratropium + Theophylline SR | Pre-dose PEF in First Week of Treatment | 3.257 L/min |
p-value: <0.000195% CI: [12.163, 30.11]ANCOVA
Secondary
Pre-dose PEF in Last Week of Treatment
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Pre-dose PEF in Last Week of Treatment | 23.135 L/min |
| Ipratropium + Theophylline SR | Pre-dose PEF in Last Week of Treatment | -2.038 L/min |
p-value: 0.000195% CI: [12.733, 37.611]ANCOVA
Secondary
Pre-dose PEF in Whole Treatment Period
Change in pre-dose morning PEF from run-in period to whole treatment period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Pre-dose PEF in Whole Treatment Period | 21.021 L/min |
| Ipratropium + Theophylline SR | Pre-dose PEF in Whole Treatment Period | -2.023 L/min |
p-value: <0.000195% CI: [14.927, 31.161]ANCOVA
Secondary
Use of Reliever Medication During Day in the First Week on Treatment
Change in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Use of Reliever Medication During Day in the First Week on Treatment | -0.440 times/day |
| Ipratropium + Theophylline SR | Use of Reliever Medication During Day in the First Week on Treatment | -0.097 times/day |
p-value: 0.000495% CI: [-0.533, -0.153]ANCOVA
Secondary
Use of Reliever Medication During Day in the Last Week on Treatment
Change in the number of inhalations of reliever medication during day from run-in to the last week on treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Use of Reliever Medication During Day in the Last Week on Treatment | -0.398 times/day |
| Ipratropium + Theophylline SR | Use of Reliever Medication During Day in the Last Week on Treatment | -0.101 times/day |
p-value: 0.010295% CI: [-0.522, -0.071]ANCOVA
Secondary
Use of Reliever Medication During Day in the Whole Treatment Period
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Use of Reliever Medication During Day in the Whole Treatment Period | -0.404 times/day |
| Ipratropium + Theophylline SR | Use of Reliever Medication During Day in the Whole Treatment Period | -0.061 times/day |
p-value: 0.000295% CI: [-0.523, -0.162]ANCOVA
Secondary
Use of Reliever Medication During Night in the First Week on Treatment
change in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Use of Reliever Medication During Night in the First Week on Treatment | -0.124 times/day |
| Ipratropium + Theophylline SR | Use of Reliever Medication During Night in the First Week on Treatment | -0.002 times/day |
p-value: 0.00195% CI: [-0.194, -0.049]ANCOVA
Secondary
Use of Reliever Medication During Night in the Last Week on Treatment
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the last week on treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Use of Reliever Medication During Night in the Last Week on Treatment | -0.078 times/day |
| Ipratropium + Theophylline SR | Use of Reliever Medication During Night in the Last Week on Treatment | -0.023 times/day |
p-value: 0.228195% CI: [-0.144, 0.035]ANCOVA
Secondary
Use of Reliever Medication During Night in the Whole Treatment Period
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Time frame: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the whole treatment period (12 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | Use of Reliever Medication During Night in the Whole Treatment Period | -0.086 times/day |
| Ipratropium + Theophylline SR | Use of Reliever Medication During Night in the Whole Treatment Period | 0.020 times/day |
p-value: 0.007395% CI: [-0.183, -0.029]ANCOVA