Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD
Brief summary
The purpose of this study is to show the efficacy and safety of formoterol for the maintenance treatment of patients with COPD compared with placebo in patients in Japan and in European countries during 12 weeks.
Interventions
DRUGFormoterol Turbuhaler® 4.5mg
4.5 mg inhaled twice daily
DRUGFormoterol Turbuhaler® 9 mg
9 mg inhaled twice daily
DRUGTurbuhaler® placebo
placebo inhaled twice daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females aged above 40 with a clinical diagnosis of COPD and current COPD symptoms * Current or previous smoker with a smoking history of 10 or more pack years * Lung function parameters: FEV1/FVC \< 70%, post-bronchodilator and post-bronchodilator FEV1 \< 80% of predicted normal value
Exclusion criteria
* History and/or current clinical diagnosis of asthma or atopic diseases such as allergic rhinitis * Use of inhaled glucocorticosteroids within 4 weeks prior to Visit 2 * Any relevant cardiovascular disorder as judged by the investigator or any current respiratory tract disorder other than COPD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1; L) 60 Minutes Post-dose | from baseline up to 12 weeks | FEV1 (expressed as litres \[L\]) is a spirometric measure of lung function. FEV1 was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Pre-dose | baseline at week 0 and pre-dose at weeks 4, 8 and 12 | Lung function (FEV1) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value |
| FVC Pre-dose | baseline at week 0 and pre-dose at weeks 4, 8 and 12 | Lung function (FVC) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value |
| FEV1 5 Minutes Post-dose | baseline and 5 minutes anter first dose | Lung function (FEV1) was measured 5 minutes after the first dose of study drug. The results are expressed as a percentage in relation to the baseline value |
| FVC 5 Minutes Post-dose | baseline and 5 minutes anter first dose | Lung function (FVC) was measured 5 minutes after the first dose of study drug, The results are expressed as a percentage in relation to the baseline value |
| Change in Peak Expiratory Flow (PEF), Morning | run-in period and 12 week | Patients were asked to measure and record lung function (peak expiratory flow \[PEF\] measured in the morning). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value |
| Forced Vital Capacity (FVC) 60 Minutes Post-dose | from baseline up to 12 weeks | Forced Vital Capacity (FVC) is a spirometric measure of lung function. FVC was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value |
| Change in Night-time Awakenings Due to Symptoms | run-in period up to 12 weeks | Patients were asked to record the night-time awakenings due to symptoms (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value |
| Breathlessness | run-in period up to 12 weeks | Patients were asked to record breathlessness (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value |
| Cough | run-in period up to 12 weeks | Patients were asked to record cough (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value |
| Use of Reliever Medication | 12 weeks (end of run-in to last visit) | Patients were asked to record reliever medication use. Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value |
| St George's Respiratory Questionnaire (SGRQ) | 12 weeks (end of run-in to last visit) | Patients were asked to complete the St George's Respiratory Questionnaire (SGRQ). Subscale symptom score ranges from 0 to 100% and measures the effect of respiratory symptoms, frequency, and severity on quality of life. A score of 0 indicates the best possible status. Results are expressed as the change from baseline score with a decrease in score indicating improvement. |
| Change in Peak Expiratory Flow (PEF), Evening | run-in period and 12 week | Patients were asked to measure and record lung function (peak expiratory flow \[PEF\] measured in the evening). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value |
Countries
Bulgaria, Japan, Romania, Russia, Ukraine
Participant flow
Recruitment details
Outpatients, male or female aged ≥ 40 years with moderate to severe chronic obstructive pulmonary disease (COPD). 766 subjects enrolled; 153 excluded: 96 for incorrect enrollment, 17 for adverse events, 32 for voluntary discontinuation, 1 for non-compliance with protocol, 7 for other reasons. 613 were randomised.
Participants by arm
| Arm | Count |
|---|---|
| Formoterol 4.5 Bid Formoterol 4.5 ug bid | 206 |
| Formoterol 9.0 Bid Formoterol 9.0 ug bid | 199 |
| Placebo Placebo | 208 |
| Total | 613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 8 | 10 |
| Overall Study | COPD Exacerbation | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 6 | 11 |
Baseline characteristics
| Characteristic | Formoterol 4.5 Bid | Formoterol 9.0 Bid | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 66.7 Years STANDARD_DEVIATION 9.4 | 67.2 Years STANDARD_DEVIATION 9.2 | 66.3 Years STANDARD_DEVIATION 9.7 | 66.75 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 23 Participants | 29 Participants | 22 Participants | 74 Participants |
| Sex: Female, Male Male | 183 Participants | 170 Participants | 186 Participants | 539 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 206 | 31 / 199 | 31 / 208 |
| serious Total, serious adverse events | 6 / 206 | 7 / 199 | 4 / 208 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1; L) 60 Minutes Post-dose
FEV1 (expressed as litres \[L\]) is a spirometric measure of lung function. FEV1 was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value.
Time frame: from baseline up to 12 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol 4.5 Bid | Forced Expiratory Volume in 1 Second (FEV1; L) 60 Minutes Post-dose | 112.9 percent of baseline |
| Formoterol 9.0 Bid | Forced Expiratory Volume in 1 Second (FEV1; L) 60 Minutes Post-dose | 113.36 percent of baseline |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1; L) 60 Minutes Post-dose | 101.28 percent of baseline |
Secondary
Breathlessness
Patients were asked to record breathlessness (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value
Time frame: run-in period up to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | Breathlessness | -0.4068 scores on a scale per day | Standard Deviation 0.6193 |
| Formoterol 9.0 Bid | Breathlessness | -0.4531 scores on a scale per day | Standard Deviation 0.5511 |
| Placebo | Breathlessness | -0.2626 scores on a scale per day | Standard Deviation 0.5899 |
Secondary
Change in Night-time Awakenings Due to Symptoms
Patients were asked to record the night-time awakenings due to symptoms (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value
Time frame: run-in period up to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | Change in Night-time Awakenings Due to Symptoms | -0.1318 scores on a scale per day | Standard Deviation 0.4791 |
| Formoterol 9.0 Bid | Change in Night-time Awakenings Due to Symptoms | -0.1748 scores on a scale per day | Standard Deviation 0.5517 |
| Placebo | Change in Night-time Awakenings Due to Symptoms | -0.0466 scores on a scale per day | Standard Deviation 0.49 |
Secondary
Change in Peak Expiratory Flow (PEF), Evening
Patients were asked to measure and record lung function (peak expiratory flow \[PEF\] measured in the evening). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value
Time frame: run-in period and 12 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | Change in Peak Expiratory Flow (PEF), Evening | 13.15 L/min | Standard Deviation 27.52 |
| Formoterol 9.0 Bid | Change in Peak Expiratory Flow (PEF), Evening | 15.76 L/min | Standard Deviation 25.22 |
| Placebo | Change in Peak Expiratory Flow (PEF), Evening | 2.36 L/min | Standard Deviation 26.43 |
Secondary
Change in Peak Expiratory Flow (PEF), Morning
Patients were asked to measure and record lung function (peak expiratory flow \[PEF\] measured in the morning). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value
Time frame: run-in period and 12 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | Change in Peak Expiratory Flow (PEF), Morning | 16.27 L/min | Standard Deviation 27.9 |
| Formoterol 9.0 Bid | Change in Peak Expiratory Flow (PEF), Morning | 18.34 L/min | Standard Deviation 26.19 |
| Placebo | Change in Peak Expiratory Flow (PEF), Morning | 3.60 L/min | Standard Deviation 27.08 |
Secondary
Cough
Patients were asked to record cough (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value
Time frame: run-in period up to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | Cough | -0.3250 scores on a scale per day | Standard Deviation 0.6424 |
| Formoterol 9.0 Bid | Cough | -0.4088 scores on a scale per day | Standard Deviation 0.6374 |
| Placebo | Cough | -0.2016 scores on a scale per day | Standard Deviation 0.6233 |
Secondary
FEV1 5 Minutes Post-dose
Lung function (FEV1) was measured 5 minutes after the first dose of study drug. The results are expressed as a percentage in relation to the baseline value
Time frame: baseline and 5 minutes anter first dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol 4.5 Bid | FEV1 5 Minutes Post-dose | 110.16 percent of baseline |
| Formoterol 9.0 Bid | FEV1 5 Minutes Post-dose | 110.24 percent of baseline |
| Placebo | FEV1 5 Minutes Post-dose | 101.25 percent of baseline |
Secondary
FEV1 Pre-dose
Lung function (FEV1) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value
Time frame: baseline at week 0 and pre-dose at weeks 4, 8 and 12
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol 4.5 Bid | FEV1 Pre-dose | 104.54 percent of baseline |
| Formoterol 9.0 Bid | FEV1 Pre-dose | 104.65 percent of baseline |
| Placebo | FEV1 Pre-dose | 99.77 percent of baseline |
Secondary
Forced Vital Capacity (FVC) 60 Minutes Post-dose
Forced Vital Capacity (FVC) is a spirometric measure of lung function. FVC was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value
Time frame: from baseline up to 12 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol 4.5 Bid | Forced Vital Capacity (FVC) 60 Minutes Post-dose | 109.73 percent of baseline |
| Formoterol 9.0 Bid | Forced Vital Capacity (FVC) 60 Minutes Post-dose | 109.92 percent of baseline |
| Placebo | Forced Vital Capacity (FVC) 60 Minutes Post-dose | 102.11 percent of baseline |
Secondary
FVC 5 Minutes Post-dose
Lung function (FVC) was measured 5 minutes after the first dose of study drug, The results are expressed as a percentage in relation to the baseline value
Time frame: baseline and 5 minutes anter first dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol 4.5 Bid | FVC 5 Minutes Post-dose | 108.50 percent of baseline |
| Formoterol 9.0 Bid | FVC 5 Minutes Post-dose | 108.88 percent of baseline |
| Placebo | FVC 5 Minutes Post-dose | 101.59 percent of baseline |
Secondary
FVC Pre-dose
Lung function (FVC) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value
Time frame: baseline at week 0 and pre-dose at weeks 4, 8 and 12
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol 4.5 Bid | FVC Pre-dose | 103.62 percent of baseline |
| Formoterol 9.0 Bid | FVC Pre-dose | 103.36 percent of baseline |
| Placebo | FVC Pre-dose | 100.73 percent of baseline |
Secondary
St George's Respiratory Questionnaire (SGRQ)
Patients were asked to complete the St George's Respiratory Questionnaire (SGRQ). Subscale symptom score ranges from 0 to 100% and measures the effect of respiratory symptoms, frequency, and severity on quality of life. A score of 0 indicates the best possible status. Results are expressed as the change from baseline score with a decrease in score indicating improvement.
Time frame: 12 weeks (end of run-in to last visit)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | St George's Respiratory Questionnaire (SGRQ) | -5.46 Scores on a scale | Standard Deviation 12.12 |
| Formoterol 9.0 Bid | St George's Respiratory Questionnaire (SGRQ) | -6.38 Scores on a scale | Standard Deviation 10.77 |
| Placebo | St George's Respiratory Questionnaire (SGRQ) | -2.02 Scores on a scale | Standard Deviation 12.98 |
Secondary
Use of Reliever Medication
Patients were asked to record reliever medication use. Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value
Time frame: 12 weeks (end of run-in to last visit)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 4.5 Bid | Use of Reliever Medication | -0.60 medication doses per day | Standard Deviation 1.47 |
| Formoterol 9.0 Bid | Use of Reliever Medication | -0.97 medication doses per day | Standard Deviation 1.88 |
| Placebo | Use of Reliever Medication | -0.23 medication doses per day | Standard Deviation 1.25 |