Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Severe chronic obstructive pulmonary disease (COPD) patients
Brief summary
This is a multicentre study with a randomised, parallel group, open-label, 3-month phase IV design to assess the efficacy and tolerability of Symbicort as an add-on treatment to Spiriva compare with Spiriva alone in patients with severe chronic obstructive pulmonary disease (COPD).
Interventions
DRUGBudesonide/formoterol (Symbicort® Turbuhaler®)
Budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5μg/inhalation, 2 inhalations twice daily
DRUGTiotropium (SpirivaTM)
Tiotropium (SpirivaTM) 18 μg/inhalation, 1 inhalation once 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 and also the patients who use of systemic glucocorticosteroids (GCS) within 4 weeks and/or inhaled GCS within 2 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 (measured 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 (measured 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) in treatment period to baseline value |
| Post-dose FVC at 5 Minutes | Baseline (measured 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 value |
| Post-dose FVC at 60 Minutes | Baseline (measured 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 value |
| Pre-dose IC | Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug | Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value |
| Post-dose IC at 60 Minutes | Baseline (measured 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 value |
| 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, up to 12 weeks | 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 measurements measured before inhalation of study drug in the first week of treatment | Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of 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 period to the first week on 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 of 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, up to 12 weeks | Change in post-dose morning PEF at 5 minutes from run-period to last 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 |
| 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 of 12 weeks | Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period |
| 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, up to 12 weeks | Change in the number of inhalations of reliever medication during day from run-in period to the last 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 of 12 weeks | Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period |
| 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 day in the last week on treatment, up to 12 weeks | Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment |
| 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 period 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 day in the whole treatment period of 12 weeks | Change in the number of inhalations of reliever medication during night from run-in period 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 of 12 weeks | Change in breathing symptom score (from 0:none to 4:severe) from run-in period |
| Change in 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 of 12 weeks | Change in Cough symptom score (from 0:none to 4:severe) from run-in period |
| Change in 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 of 12 weeks | Change in Sputum symptom score (from 0:none to 4:severe) from run-in period |
| COPD Exacerbations | Whole treatment period of 12 weeks | Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms |
| 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 measurements 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 |
Countries
China, Hong Kong, Indonesia, South Korea, Thailand
Participant flow
Recruitment details
There are 793 patients enrolled. 578 patients were randomized, where there are 287 patients randomized in Symbicort+ Spiriva group and 291 in Spiriva group
Participants by arm
| Arm | Count |
|---|---|
| Symbicort+Spiriva Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily) | 287 |
| Spiriva Spiriva 18 μg/inhalation, 1 inhalation once daily | 290 |
| Total | 577 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Condition under Investigation Worsened | 1 | 3 |
| Overall Study | Death | 2 | 3 |
| Overall Study | Eligibility Criteria Not Fulfilled | 7 | 6 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Others | 2 | 1 |
| Overall Study | Severe Non-Compliance to Protocol | 2 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 11 |
Baseline characteristics
| Characteristic | Symbicort+Spiriva | Spiriva | Total |
|---|---|---|---|
| Age, Continuous | 66.6 Years STANDARD_DEVIATION 7.99 | 66.9 Years STANDARD_DEVIATION 8.5 | 66.8 Years STANDARD_DEVIATION 8.25 |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 25 Participants |
| Sex: Female, Male Male | 279 Participants | 273 Participants | 552 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 289 | 76 / 289 |
| serious Total, serious adverse events | 14 / 289 | 24 / 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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Pre-dose FEV1 | 1.050 Ratio |
| Spiriva | Pre-dose FEV1 | 1.006 Ratio |
p-value: 0.000495% CI: [1.019, 1.069]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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Change in COPD Symptoms - Breathing | -0.372 score on a scale |
| Spiriva | Change in COPD Symptoms - Breathing | -0.110 score on a scale |
p-value: <0.000195% CI: [-0.364, -0.159]ANCOVA
Secondary
Change in COPD Symptoms - Cough
Change in Cough 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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Change in COPD Symptoms - Cough | -0.311 score on a scale |
| Spiriva | Change in COPD Symptoms - Cough | -0.169 score on a scale |
p-value: 0.006795% CI: [-0.246, -0.04]ANCOVA
Secondary
Change in 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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Change in COPD Symptoms - Sputum | -0.216 score on a scale |
| Spiriva | Change in COPD Symptoms - Sputum | -0.094 score on a scale |
p-value: 0.017195% CI: [-0.222, -0.022]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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | COPD Exacerbations | 0.182 exacerbations/participant/12 weeks |
| Spiriva | COPD Exacerbations | 0.307 exacerbations/participant/12 weeks |
p-value: 0.003295% CI: [0.419, 0.839]Poisson regression
p-value: 0.016795% CI: [0.412, 0.916]Regression, Cox
p-value: 0.0196Log Rank
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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose FEV1 at 5 Minutes | 1.128 Ratio |
| Spiriva | Post-dose FEV1 at 5 Minutes | 1.045 Ratio |
p-value: <0.000195% CI: [1.057, 1.102]ANCOVA
Secondary
Post-dose FEV1 at 60 Minutes
Ratio of post-dose FEV1 at 60 minutes to baseline value
Time frame: Baseline (measured 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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose FEV1 at 60 Minutes | 1.164 Ratio |
| Spiriva | Post-dose FEV1 at 60 Minutes | 1.072 Ratio |
p-value: <0.000195% CI: [1.062, 1.111]ANCOVA
Secondary
Post-dose FVC at 5 Minutes
Ratio of post-dose FVC at 5 minutes to baseline value
Time frame: Baseline (measured 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)
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose FVC at 5 Minutes | 1.096 Ratio |
| Spiriva | Post-dose FVC at 5 Minutes | 1.044 Ratio |
p-value: <0.000195% CI: [1.033, 1.067]ANCOVA
Secondary
Post-dose FVC at 60 Minutes
Ratio of post-dose FVC at 60 minutes to baseline value
Time frame: Baseline (measured 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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose FVC at 60 Minutes | 1.116 Ratio |
| Spiriva | Post-dose FVC at 60 Minutes | 1.059 Ratio |
p-value: <0.000195% CI: [1.036, 1.073]ANCOVA
Secondary
Post-dose IC at 60 Minutes
Ratio of post-dose IC at 60 minutes to baseline value
Time frame: Baseline (measured 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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose IC at 60 Minutes | 1.154 Ratio |
| Spiriva | Post-dose IC at 60 Minutes | 1.087 Ratio |
p-value: <0.000195% CI: [1.035, 1.091]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 measurements measured at 5 minutes after inhalation of study drug in the first week of treatment
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose PEF in First Week of Treatment | 17.412 L/min |
| Spiriva | Post-dose PEF in First Week of Treatment | 0.220 L/min |
p-value: 0.000695% CI: [7.491, 26.894]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, up to 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose PEF in Last Week of Treatment | 23.379 L/min |
| Spiriva | Post-dose PEF in Last Week of Treatment | -3.049 L/min |
p-value: 0.000195% CI: [13.463, 39.393]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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Post-dose PEF in Whole Treatment Period | 15.880 L/min |
| Spiriva | Post-dose PEF in Whole Treatment Period | -2.591 L/min |
p-value: <0.000195% CI: [10.347, 26.596]ANCOVA
Secondary
Pre-dose FVC
Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value
Time frame: Baseline (measured 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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Pre-dose FVC | 1.032 Ratio |
| Spiriva | Pre-dose FVC | 1.013 Ratio |
p-value: 0.05795% CI: [0.999, 1.037]ANCOVA
Secondary
Pre-dose IC
Ratio of pre-dose IC (Inspiratory Capacity) 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 (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Pre-dose IC | 1.042 Ratio |
| Spiriva | Pre-dose IC | 1.022 Ratio |
p-value: 0.195695% CI: [0.99, 1.05]ANCOVA
Secondary
Pre-dose PEF in First Week of Treatment
Change in pre-dose morning PEF (Peak Expiratory Flow) 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 measurements measured before inhalation of study drug in the first week of treatment
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Pre-dose PEF in First Week of Treatment | 13.405 L/min |
| Spiriva | Pre-dose PEF in First Week of Treatment | -0.182 L/min |
p-value: <0.000195% CI: [7.407, 19.766]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, up to 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Pre-dose PEF in Last Week of Treatment | 15.753 L/min |
| Spiriva | Pre-dose PEF in Last Week of Treatment | -4.550 L/min |
p-value: 0.000195% CI: [9.904, 30.702]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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Pre-dose PEF in Whole Treatment Period | 12.271 L/min |
| Spiriva | Pre-dose PEF in Whole Treatment Period | -5.198 L/min |
p-value: <0.000195% CI: [10.147, 24.791]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 period 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
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Use of Reliever Medication During Day in the First Week on Treatment | -0.457 times/day |
| Spiriva | Use of Reliever Medication During Day in the First Week on Treatment | -0.082 times/day |
p-value: <0.000195% CI: [-0.552, -0.198]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 period 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, up to 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Use of Reliever Medication During Day in the Last Week on Treatment | -0.750 times/day |
| Spiriva | Use of Reliever Medication During Day in the Last Week on Treatment | -0.082 times/day |
p-value: <0.000195% CI: [-0.9, -0.437]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 period 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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Use of Reliever Medication During Day in the Whole Treatment Period | -0.685 times/day |
| Spiriva | Use of Reliever Medication During Day in the Whole Treatment Period | -0.134 times/day |
p-value: <0.000195% CI: [-0.741, -0.361]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 period 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
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Use of Reliever Medication During Night in the First Week on Treatment | -0.113 times/day |
| Spiriva | Use of Reliever Medication During Night in the First Week on Treatment | 0.011 times/day |
p-value: 0.037295% CI: [-0.24, -0.007]ANCOVA
Secondary
Use of Reliever Medication During Night in the Last Week on Treatment
Change in the number of inhalations of reliever medication during night from run-in period 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, up to 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Use of Reliever Medication During Night in the Last Week on Treatment | -0.174 times/day |
| Spiriva | Use of Reliever Medication During Night in the Last Week on Treatment | 0.062 times/day |
p-value: 0.002895% CI: [-0.391, -0.082]ANCOVA
Secondary
Use of Reliever Medication During Night in the Whole Treatment Period
Change in the number of inhalations of reliever medication during night from run-in period 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 of 12 weeks
Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Symbicort+Spiriva | Use of Reliever Medication During Night in the Whole Treatment Period | -0.241 times/day |
| Spiriva | Use of Reliever Medication During Night in the Whole Treatment Period | -0.010 times/day |
p-value: 0.000195% CI: [-0.35, -0.113]ANCOVA