Chronic Obstructive Pulmonary Disease, COPD
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD
Brief summary
The purpose of this study is to investigate the effect of combined treatment with Symbicort and Spiriva, in terms of improvement of lung function, symptoms and inflammatory markers, in patients with severe COPD.
Interventions
DRUGSymbicort (budesonide/formoterol turbuhaler 320/9ug)
Symbicort (budesonide/formoterol turbuhaler 320/9ug)
DRUGSpiriva (tiotropium bromide 18ug)
Spiriva (tiotropium bromide 18ug)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>=40 years of age, diagnosed COPD with symptoms \>=2 years, pre-bronchodilatory FEV1 \<=50% of PN
Exclusion criteria
* Current respiratory tract disorder other than COPD, history of asthma or rhinitis, significant or unstable cardiovascular disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) Pre-dose | Baseline to 12 weeks | Change in the pre-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose | Baseline to 12 weeks | Change in the 60 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
| Forced Vital Capacity (FVC) Pre-dose | Baseline to 12 weeks | Change in the pre-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
| Forced Vital Capacity (FVC) 5 Minutes Post-dose | Baseline to 12 weeks | Change in the 5 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
| Forced Vital Capacity (FVC) 60 Minutes Post-dose | Baseline to 12 weeks | Change in the 60 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12 |
| Inspiratory Capacity (IC) Pre-dose | Baseline to 12 weeks | Change in the pre-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
| Inspiratory Capacity (IC) 60 Minutes Post-dose | Baseline to 12 weeks | Change in the 60 min post-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
| St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score | Baseline and 12 weeks | Change in total score from baseline (Visit 3) to end of treatment (Visit 6, or last available visit). SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. |
| Morning Peak Expiratory Flow (PEF) Pre-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Evening Peak Expiratory Flow (PEF) Pre-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Morning Peak Expiratory Flow (PEF) 15 Min Post-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Morning Diary FEV1 Pre-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Morning Peak Expiratory Flow (PEF) 5 Min Post-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Evening Diary FEV1, Pre-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Morning Diary FEV1, 5 Minutes Post-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Morning Diary FEV1, 15 Minutes Post-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period |
| Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions. |
| GCSQ Score, 5 Minutes Post-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions. |
| Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose | Baseline to 12 weeks | Change in the 5 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) |
| Capacity of Day Living in the Morning (CDLM) Score | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. The CDLM questionnaire is as a questionnaire to report on patient's ability to carry out each of six different morning activities (score ranging from 0 not performed to 1performed) and rank the difficulty of performing each of those activities (score ranging from 0 so difficult that the activity could not be carried out by the patient on their own to 5 activity was not at all difficult to carry out. Total score for each morning activity range from 0-6. Total score for whole CDLM questionnaire range from 0-36. |
| Use of Rescue Medication, Night | Baseline to 12 weeks | Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period |
| Use of Rescue Medication, Morning | Baseline to 12 weeks | Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period |
| Use of Rescue Medication, Day | Baseline to 12 weeks | Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period |
| Use of Rescue Medication, Total | Baseline to 12 weeks | Daily diary record - Total, 24 hours, during the night, and during the day. Change in average values from run-in to the full treatment period |
| COPD Symptoms, Breathing Score | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe |
| COPD Symptoms, Sleeping Score | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe |
| COPD Symptoms, Chest Score | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe |
| COPD Symptoms, Cough Score | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe |
| Severe COPD Exacerbations | 12 weeks | Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation |
| Serum High-sensitivity C-reactive Protein (hsCRP) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| Serum Interleukin 6 (IL-6) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| Serum Interleukin 8 (IL-8) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| Serum Monocyte Chemoattractant Protein-1 (MCP-1) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| Serum Tumor Necrosis Factor-alpha (TNF-alpha) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) | Baseline to 12 weeks | Ratio of treatment period mean to run-in value |
| GCSQ Score, 15 Minutes Post-dose | Baseline to 12 weeks | Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions. |
Countries
Australia, Canada, France, Germany, Hungary, Poland, Slovakia, Spain, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Symbicort+Tiotropium Symbicort Turbuhaler® (budesonide/formoterol) 320/9 mcg, one inhalation twice daily and Spiriva® (tiotropium) 18 mcg, one inhalation once daily | 329 |
| Placebo+Tiotropium Spiriva® (tiotropium) 18 mcg, one inhalation once daily and placebo Turbuhaler one inhalation once daily | 331 |
| Total | 660 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 10 |
| Overall Study | Incorrectly enrolled | 13 | 5 |
| Overall Study | Other reason | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 12 |
Baseline characteristics
| Characteristic | Symbicort+Tiotropium | Placebo+Tiotropium | Total |
|---|---|---|---|
| Age Continuous | 62.4 Years | 62.5 Years | 62.45 Years |
| Sex: Female, Male Female | 78 Participants | 86 Participants | 164 Participants |
| Sex: Female, Male Male | 251 Participants | 245 Participants | 496 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 329 | 0 / 330 |
| serious Total, serious adverse events | 10 / 329 | 16 / 330 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1) Pre-dose
Change in the pre-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Forced Expiratory Volume in 1 Second (FEV1) Pre-dose | 0.064 Liters | Standard Deviation 0.198 |
| Placebo+Tiotropium | Forced Expiratory Volume in 1 Second (FEV1) Pre-dose | -0.001 Liters | Standard Deviation 0.168 |
Secondary
Capacity of Day Living in the Morning (CDLM) Score
Daily diary record. Change in average values from run-in to the full treatment period. The CDLM questionnaire is as a questionnaire to report on patient's ability to carry out each of six different morning activities (score ranging from 0 not performed to 1performed) and rank the difficulty of performing each of those activities (score ranging from 0 so difficult that the activity could not be carried out by the patient on their own to 5 activity was not at all difficult to carry out. Total score for each morning activity range from 0-6. Total score for whole CDLM questionnaire range from 0-36.
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Capacity of Day Living in the Morning (CDLM) Score | 0.202 Scores on a scale | Standard Deviation 0.467 |
| Placebo+Tiotropium | Capacity of Day Living in the Morning (CDLM) Score | 0.07 Scores on a scale | Standard Deviation 0.435 |
Secondary
COPD Symptoms, Breathing Score
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | COPD Symptoms, Breathing Score | -0.177 Units on a Scale | Standard Deviation 0.503 |
| Placebo+Tiotropium | COPD Symptoms, Breathing Score | -0.049 Units on a Scale | Standard Deviation 0.5 |
Secondary
COPD Symptoms, Chest Score
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | COPD Symptoms, Chest Score | -0.184 Units on a Scale | Standard Deviation 0.5 |
| Placebo+Tiotropium | COPD Symptoms, Chest Score | -0.061 Units on a Scale | Standard Deviation 0.473 |
Secondary
COPD Symptoms, Cough Score
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | COPD Symptoms, Cough Score | -0.246 Units on a Scale | Standard Deviation 0.567 |
| Placebo+Tiotropium | COPD Symptoms, Cough Score | -0.079 Units on a Scale | Standard Deviation 0.545 |
Secondary
COPD Symptoms, Sleeping Score
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | COPD Symptoms, Sleeping Score | -0.197 Units on a Scale | Standard Deviation 0.45 |
| Placebo+Tiotropium | COPD Symptoms, Sleeping Score | -0.045 Units on a Scale | Standard Deviation 0.462 |
Secondary
Evening Diary FEV1, Pre-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Evening Diary FEV1, Pre-dose | 0.012 Liters | Standard Deviation 0.223 |
| Placebo+Tiotropium | Evening Diary FEV1, Pre-dose | -0.065 Liters | Standard Deviation 0.249 |
Secondary
Evening Peak Expiratory Flow (PEF) Pre-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Evening Peak Expiratory Flow (PEF) Pre-dose | 2.82 Liters/minute | Standard Deviation 37.6 |
| Placebo+Tiotropium | Evening Peak Expiratory Flow (PEF) Pre-dose | -5.54 Liters/minute | Standard Deviation 28.9 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose
Change in the 5 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose | 0.165 Liters | Standard Deviation 0.184 |
| Placebo+Tiotropium | Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose | 0.042 Liters | Standard Deviation 0.14 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose
Change in the 60 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose | 0.214 Liters | Standard Deviation 0.209 |
| Placebo+Tiotropium | Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose | 0.083 Liters | Standard Deviation 0.157 |
Secondary
Forced Vital Capacity (FVC) 5 Minutes Post-dose
Change in the 5 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Forced Vital Capacity (FVC) 5 Minutes Post-dose | 0.266 Liters | Standard Deviation 0.32 |
| Placebo+Tiotropium | Forced Vital Capacity (FVC) 5 Minutes Post-dose | 0.106 Liters | Standard Deviation 0.296 |
Secondary
Forced Vital Capacity (FVC) 60 Minutes Post-dose
Change in the 60 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Forced Vital Capacity (FVC) 60 Minutes Post-dose | 0.353 Liters | Standard Deviation 0.357 |
| Placebo+Tiotropium | Forced Vital Capacity (FVC) 60 Minutes Post-dose | 0.19 Liters | Standard Deviation 0.319 |
Secondary
Forced Vital Capacity (FVC) Pre-dose
Change in the pre-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Forced Vital Capacity (FVC) Pre-dose | 0.07 Liters | Standard Deviation 0.341 |
| Placebo+Tiotropium | Forced Vital Capacity (FVC) Pre-dose | 0.014 Liters | Standard Deviation 0.348 |
Secondary
GCSQ Score, 15 Minutes Post-dose
Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | GCSQ Score, 15 Minutes Post-dose | -0.404 Scores on a scale | Standard Deviation -0.526 |
| Placebo+Tiotropium | GCSQ Score, 15 Minutes Post-dose | -0.28 Scores on a scale | Standard Deviation -0.501 |
Secondary
GCSQ Score, 5 Minutes Post-dose
Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions.
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | GCSQ Score, 5 Minutes Post-dose | -0.325 Scores on a scale | Standard Deviation 0.508 |
| Placebo+Tiotropium | GCSQ Score, 5 Minutes Post-dose | -0.202 Scores on a scale | Standard Deviation 0.46 |
Secondary
Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose
Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions.
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose | -0.143 Scores on a scale | Standard Deviation 0.453 |
| Placebo+Tiotropium | Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose | -0.006 Scores on a scale | Standard Deviation 0.438 |
Secondary
Inspiratory Capacity (IC) 60 Minutes Post-dose
Change in the 60 min post-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Inspiratory Capacity (IC) 60 Minutes Post-dose | 0.26 Liters | Standard Deviation 0.353 |
| Placebo+Tiotropium | Inspiratory Capacity (IC) 60 Minutes Post-dose | 0.149 Liters | Standard Deviation 0.359 |
Secondary
Inspiratory Capacity (IC) Pre-dose
Change in the pre-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Inspiratory Capacity (IC) Pre-dose | 0.078 Liters | Standard Deviation 0.35 |
| Placebo+Tiotropium | Inspiratory Capacity (IC) Pre-dose | 0.014 Liters | Standard Deviation 0.389 |
Secondary
Morning Diary FEV1, 15 Minutes Post-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Morning Diary FEV1, 15 Minutes Post-dose | 0.209 Liters | Standard Deviation 0.236 |
| Placebo+Tiotropium | Morning Diary FEV1, 15 Minutes Post-dose | 0.014 Liters | Standard Deviation 0.201 |
Secondary
Morning Diary FEV1, 5 Minutes Post-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Morning Diary FEV1, 5 Minutes Post-dose | 0.169 Liters | Standard Deviation 0.224 |
| Placebo+Tiotropium | Morning Diary FEV1, 5 Minutes Post-dose | -0.018 Liters | Standard Deviation 0.189 |
Secondary
Morning Diary FEV1 Pre-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Morning Diary FEV1 Pre-dose | 0.054 Liters | Standard Deviation 0.201 |
| Placebo+Tiotropium | Morning Diary FEV1 Pre-dose | -0.046 Liters | Standard Deviation 0.185 |
Secondary
Morning Peak Expiratory Flow (PEF) 15 Min Post-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Morning Peak Expiratory Flow (PEF) 15 Min Post-dose | 20.4 Liters/minute | Standard Deviation 43.7 |
| Placebo+Tiotropium | Morning Peak Expiratory Flow (PEF) 15 Min Post-dose | 5.2 Liters/minute | Standard Deviation 28.3 |
Secondary
Morning Peak Expiratory Flow (PEF) 5 Min Post-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Morning Peak Expiratory Flow (PEF) 5 Min Post-dose | 16.71 Liters/minute | Standard Deviation 42.6 |
| Placebo+Tiotropium | Morning Peak Expiratory Flow (PEF) 5 Min Post-dose | 1.1 Liters/minute | Standard Deviation 26.5 |
Secondary
Morning Peak Expiratory Flow (PEF) Pre-dose
Daily diary record. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Morning Peak Expiratory Flow (PEF) Pre-dose | 5.12 Liters/minute | Standard Deviation 38.3 |
| Placebo+Tiotropium | Morning Peak Expiratory Flow (PEF) Pre-dose | -3.52 Liters/minute | Standard Deviation 24.7 |
Secondary
Serum High-sensitivity C-reactive Protein (hsCRP)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum High-sensitivity C-reactive Protein (hsCRP) | 0.91 Ratio |
| Placebo+Tiotropium | Serum High-sensitivity C-reactive Protein (hsCRP) | 0.97 Ratio |
Secondary
Serum Interleukin 6 (IL-6)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum Interleukin 6 (IL-6) | 1.0 Ratio |
| Placebo+Tiotropium | Serum Interleukin 6 (IL-6) | 1.0 Ratio |
Secondary
Serum Interleukin 8 (IL-8)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum Interleukin 8 (IL-8) | 1.0 Ratio |
| Placebo+Tiotropium | Serum Interleukin 8 (IL-8) | 1.0 Ratio |
Secondary
Serum Monocyte Chemoattractant Protein-1 (MCP-1)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum Monocyte Chemoattractant Protein-1 (MCP-1) | 0.95 Ratio |
| Placebo+Tiotropium | Serum Monocyte Chemoattractant Protein-1 (MCP-1) | 0.95 Ratio |
Secondary
Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha) | 0.97 Ratio |
| Placebo+Tiotropium | Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha) | 0.98 Ratio |
Secondary
Serum Tumor Necrosis Factor-alpha (TNF-alpha)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum Tumor Necrosis Factor-alpha (TNF-alpha) | 1.0 Ratio |
| Placebo+Tiotropium | Serum Tumor Necrosis Factor-alpha (TNF-alpha) | 1.0 Ratio |
Secondary
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
Ratio of treatment period mean to run-in value
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Symbicort+Tiotropium | Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) | 0.96 Ratio |
| Placebo+Tiotropium | Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) | 0.99 Ratio |
Secondary
Severe COPD Exacerbations
Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation
Time frame: 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort+Tiotropium | Severe COPD Exacerbations | 25 Participants |
| Placebo+Tiotropium | Severe COPD Exacerbations | 61 Participants |
Secondary
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score
Change in total score from baseline (Visit 3) to end of treatment (Visit 6, or last available visit). SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.
Time frame: Baseline and 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score | -4.12 Score on a scale | Standard Deviation 12.81 |
| Placebo+Tiotropium | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score | -1.99 Score on a scale | Standard Deviation 12.77 |
Secondary
Use of Rescue Medication, Day
Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Use of Rescue Medication, Day | -0.745 Inhalations | Standard Deviation 1.286 |
| Placebo+Tiotropium | Use of Rescue Medication, Day | -0.371 Inhalations | Standard Deviation 1.622 |
Secondary
Use of Rescue Medication, Morning
Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Use of Rescue Medication, Morning | -0.417 Inhalations | Standard Deviation 0.758 |
| Placebo+Tiotropium | Use of Rescue Medication, Morning | -0.124 Inhalations | Standard Deviation 0.877 |
Secondary
Use of Rescue Medication, Night
Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Use of Rescue Medication, Night | -0.279 Inhalations | Standard Deviation 0.7 |
| Placebo+Tiotropium | Use of Rescue Medication, Night | 0.022 Inhalations | Standard Deviation 0.743 |
Secondary
Use of Rescue Medication, Total
Daily diary record - Total, 24 hours, during the night, and during the day. Change in average values from run-in to the full treatment period
Time frame: Baseline to 12 weeks
Population: Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort+Tiotropium | Use of Rescue Medication, Total | -1.024 Inhalations | Standard Deviation 1.704 |
| Placebo+Tiotropium | Use of Rescue Medication, Total | -0.347 Inhalations | Standard Deviation 2.102 |