Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Symbicort, Oxis, Chronic Obstructive Pulmonary Disease, COPD, Efficacy
Brief summary
The primary purpose of the study is to investigate if Symbicort is more effective than Oxis in increasing forced expiratory volume in one second (FEV1), measured at the clinics, in patients with COPD.
Interventions
DRUGBudesonide/formoterol (Symbicort Turbuhaler)
2x160/4.5 microgram, inhalation, twice daily, 12 weeks
DRUGFormoterol (Oxis Turbuhaler)
2 X 4.5 microgram, inhalation, twice daily, 12 weeks
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
* A current clinical diagnosis of Chronic Obstructive Pulmonary Disease * Documented Chronic Obstructive Pulmonary Disease symptoms for more than 2 years * A smoking history of at least 10 pack years
Exclusion criteria
* History and/or current clinical diagnosis of asthma * History and/or current clinical diagnosis of atopic diseases such as allergic rhinitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-dose Forced Expiratory Volume in One Second (FEV1) | Before randomization, 0, 4, 8 and 12 weeks after randomization | The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre-dose Forced Vital Capacity (FVC) | Before randomization, 0, 4, 8 and 12 weeks after randomization | The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group |
| 1 Hour Post-dose Forced Vital Capacity (FVC) | Before randomization, 0, 4, 8 and 12 weeks after randomization | The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group |
| Percentage of Participants With Exacerbations | Daily during 12-week randomization treatment | A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group. |
| Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Daily during 12-week randomization treatment | A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 12-week randomization treatment |
| Morning Peak Expiratory Flow(PEF) | Daily during run-in period and daily during 12-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group |
| Evening Peak Expiratory Flow (PEF) | Daily during run-in period and daily during 12-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group |
| Total Number of Day With Exacerbation | Daily during 12-week randomization treatment | Total number of days with COPD exacerbation for each treatment group |
| 1 Hour Post Dose Forced Expiratory Volume in One Second (FEV1) | Before randomization, 0, 4, 8 and 12 weeks after randomization | The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group |
| Evening Forced Expiratory Volume in One Second (FEV1) | Daily during run-in period and daily during 12-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group |
| Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | Daily during run-in period and daily during 12-week randomization treatment | Scored 0 to 1 (0 = no awakening and 1 = awakening). The change from Run-in period average to Treatment period average for each treatment group |
| Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | Daily during run-in period and daily during 12-week randomization treatment | There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group |
| Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | Daily during run-in period and daily during 12-week randomization treatment | There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group |
| Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | Daily during run-in period and daily during 12-week randomization treatment | The Total COPD Symptom score is the sum of the measures night-time awakening, breathlessness and cough, ranges from 0 to 12 with 12 being the most severe. The change from Run-in period average to Treatment period average for each treatment group. |
| Use of Rescue Medication | Daily during run-in period and daily during 12-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group. |
| St George's Respiratory Questionnaire (SGRQ) Total Score | Daily during run-in period and daily during 12-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). |
| Morning Forced Expiratory Volume in One Second (FEV1) | Daily during run-in period and daily during 12-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group |
Countries
India, Japan, Philippines, Poland, Russia, South Korea, Taiwan, Ukraine, Vietnam
Participant flow
Recruitment details
The first participant entered the study on 28 January 2010, and the last participant completed the study on 30 March 2011. A total of 1,710 participants were enrolled at 163 centres in 9 countries in Asia and Europe, and 1,293 participants who fulfilled the randomisation criteria were randomised.
Pre-assignment details
The study started with an enrolment visit, Visit 1, 0 to 4 weeks prior to Visit 2, and 1-2 week run-in period before randomization. At Visit 2 participants had to have pre-bronchodilatory forced expiratory volume in one second (FEV1) less than or equal to 50 percent of the predicted normal value.
Participants by arm
| Arm | Count |
|---|---|
| Symbicort Turbuhaler (Experimental) Symbicort Turbuhaler 160/4.5 microgram (mcg), 2 inhalations twice daily (bid) | 636 |
| Oxis Turbuhaler (Active Comparator) Oxis Turbuhaler 4.5 microgram (mcg), 2 inhalations twice daily(bid) | 657 |
| Total | 1,293 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 28 |
| Overall Study | Due to deteriorating health condition | 1 | 0 |
| Overall Study | Eligibility criteria not fulfilled | 2 | 0 |
| Overall Study | Severe non-compliance to protocol | 3 | 2 |
| Overall Study | Withdrawal by Subject | 15 | 26 |
Baseline characteristics
| Characteristic | Symbicort Turbuhaler (Experimental) | Oxis Turbuhaler (Active Comparator) | Total |
|---|---|---|---|
| Age Continuous | 64.5 Years | 65.6 Years | 65.1 Years |
| Sex: Female, Male Female | 79 Participants | 64 Participants | 143 Participants |
| Sex: Female, Male Male | 557 Participants | 593 Participants | 1150 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 636 | 66 / 657 |
| serious Total, serious adverse events | 43 / 636 | 45 / 657 |
Outcome results
Primary
Pre-dose Forced Expiratory Volume in One Second (FEV1)
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group
Time frame: Before randomization, 0, 4, 8 and 12 weeks after randomization
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | Pre-dose Forced Expiratory Volume in One Second (FEV1) | 104.6 percentage of Baseline |
| Oxis Turbuhaler (Active Comparator) | Pre-dose Forced Expiratory Volume in One Second (FEV1) | 101.5 percentage of Baseline |
Secondary
1 Hour Post Dose Forced Expiratory Volume in One Second (FEV1)
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group
Time frame: Before randomization, 0, 4, 8 and 12 weeks after randomization
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | 1 Hour Post Dose Forced Expiratory Volume in One Second (FEV1) | 113.9 percentage of Baseline |
| Oxis Turbuhaler (Active Comparator) | 1 Hour Post Dose Forced Expiratory Volume in One Second (FEV1) | 111.2 percentage of Baseline |
Secondary
1 Hour Post-dose Forced Vital Capacity (FVC)
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group
Time frame: Before randomization, 0, 4, 8 and 12 weeks after randomization
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS. Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | 1 Hour Post-dose Forced Vital Capacity (FVC) | 110.1 percentage of Baseline |
| Oxis Turbuhaler (Active Comparator) | 1 Hour Post-dose Forced Vital Capacity (FVC) | 108.7 percentage of Baseline |
Secondary
Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.34 units on a scale | Standard Deviation 0.66 |
| Oxis Turbuhaler (Active Comparator) | Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.23 units on a scale | Standard Deviation 0.65 |
Secondary
Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.24 units on a scale | Standard Deviation 0.7 |
| Oxis Turbuhaler (Active Comparator) | Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.24 units on a scale | Standard Deviation 0.68 |
Secondary
Evening Forced Expiratory Volume in One Second (FEV1)
The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Evening Forced Expiratory Volume in One Second (FEV1) | 0.0176 Liter (L) | Standard Deviation 0.2268 |
| Oxis Turbuhaler (Active Comparator) | Evening Forced Expiratory Volume in One Second (FEV1) | -0.0324 Liter (L) | Standard Deviation 0.1724 |
Secondary
Evening Peak Expiratory Flow (PEF)
The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Evening Peak Expiratory Flow (PEF) | 2.55 Liter/minute (L/min) | Standard Deviation 36.57 |
| Oxis Turbuhaler (Active Comparator) | Evening Peak Expiratory Flow (PEF) | -5.13 Liter/minute (L/min) | Standard Deviation 31.52 |
Secondary
Morning Forced Expiratory Volume in One Second (FEV1)
The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Morning Forced Expiratory Volume in One Second (FEV1) | 0.0244 Liter (L) | Standard Deviation 0.2136 |
| Oxis Turbuhaler (Active Comparator) | Morning Forced Expiratory Volume in One Second (FEV1) | -0.0312 Liter (L) | Standard Deviation 0.1712 |
Secondary
Morning Peak Expiratory Flow(PEF)
The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Morning Peak Expiratory Flow(PEF) | 4.29 Liter/minute (L/min) | Standard Deviation 36.58 |
| Oxis Turbuhaler (Active Comparator) | Morning Peak Expiratory Flow(PEF) | -4.78 Liter/minute (L/min) | Standard Deviation 30.61 |
Secondary
Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms
Scored 0 to 1 (0 = no awakening and 1 = awakening). The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.20 Nights with symptoms | Standard Deviation 0.67 |
| Oxis Turbuhaler (Active Comparator) | Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.15 Nights with symptoms | Standard Deviation 0.66 |
Secondary
Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 12-week randomization treatment
Time frame: Daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 93 event |
| Oxis Turbuhaler (Active Comparator) | Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 151 event |
Secondary
Percentage of Participants With Exacerbations
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group.
Time frame: Daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS).Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | Percentage of Participants With Exacerbations | 11.9 percentage of participants |
| Oxis Turbuhaler (Active Comparator) | Percentage of Participants With Exacerbations | 16.9 percentage of participants |
Secondary
Pre-dose Forced Vital Capacity (FVC)
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group
Time frame: Before randomization, 0, 4, 8 and 12 weeks after randomization
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | Pre-dose Forced Vital Capacity (FVC) | 102.2 percentage of Baseline |
| Oxis Turbuhaler (Active Comparator) | Pre-dose Forced Vital Capacity (FVC) | 100.9 percentage of Baseline |
Secondary
St George's Respiratory Questionnaire (SGRQ) Total Score
The change from Run-in period average to Treatment period average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life).
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | St George's Respiratory Questionnaire (SGRQ) Total Score | -4.37 units on a scale | Standard Deviation 14.544 |
| Oxis Turbuhaler (Active Comparator) | St George's Respiratory Questionnaire (SGRQ) Total Score | -2.90 units on a scale | Standard Deviation 13.783 |
Secondary
Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score
The Total COPD Symptom score is the sum of the measures night-time awakening, breathlessness and cough, ranges from 0 to 12 with 12 being the most severe. The change from Run-in period average to Treatment period average for each treatment group.
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | -0.78 units on a scale | Standard Deviation 1.62 |
| Oxis Turbuhaler (Active Comparator) | Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | -0.61 units on a scale | Standard Deviation 1.56 |
Secondary
Total Number of Day With Exacerbation
Total number of days with COPD exacerbation for each treatment group
Time frame: Daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symbicort Turbuhaler (Experimental) | Total Number of Day With Exacerbation | 653 days |
| Oxis Turbuhaler (Active Comparator) | Total Number of Day With Exacerbation | 1098 days |
Secondary
Use of Rescue Medication
The change from Run-in period average to Treatment period average for each treatment group.
Time frame: Daily during run-in period and daily during 12-week randomization treatment
Population: The analysis set for efficacy was based on the Full Analysis Set (FAS). Available data represent patients who had both baseline and on treatment data which is required to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler (Experimental) | Use of Rescue Medication | -0.51 inhalations/day | Standard Deviation 1.51 |
| Oxis Turbuhaler (Active Comparator) | Use of Rescue Medication | -0.26 inhalations/day | Standard Deviation 1.49 |