Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic, Obstructive, Pulmonary, Lung, Respiratory disease, Efficacy, Safety and tolerability, Placebo-controlled, Pharmacokinetics, COPD
Brief summary
The primary objective is to evaluate the dose-response relationship and efficacy of AZD9668 at 3 dose levels compared with placebo in symptomatic COPD patients by assessing effects on lung function and symptoms of COPD.
Interventions
DRUGAZD9668
2 x 30 mg oral tablets twice daily (bid) for 12 weeks
DRUGAZD9668 Placebo
2 x Matched placebo to oral tablet twice daily (bid) for 12 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of COPD with symptoms over 1 year * Smokers or ex-smokers * Males or post-menopausal females between 40 and 80 years old * Able to use electronic devices
Exclusion criteria
* Past history or current evidence of clinically significant heart disease * Current diagnosis of asthma * Patients who require long term oxygen therapy * Treatment with antibiotics within 4 weeks of study visit 1b
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Pre-bronchodilator FEV1 (L) | Day 1 | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic |
| End-value Pre-bronchodilator FEV1 (L) | Measured at clinic visits: 1, 4, 8 and 12 weeks | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre-bronchodilator FVC (L) - Baseline | Day 1 | Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic |
| Pre-bronchodilator FVC (L) - End-value | Measured at clinic visits: 1, 4, 8 and 12 weeks | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Post-bronchodilator FVC (L) - Baseline | Day 1 | Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic |
| Post-bronchodilator FVC (L) - End-value | Measured at clinic visits: 1, 4, 8 and 12 weeks | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Pre-bronchodilator IC (L) - Baseline | Day 1 | Inspiratory Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic |
| Pre-bronchodilator IC (L) - End-value | Measured at clinic visits: 1, 4, 8 and 12 weeks | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Post-bronchodilator IC (L) - Baseline | Day 1 | Inspiratory Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic |
| Post-bronchodilator IC (L) - End-value | Measured at clinic visits: 1, 4, 8 and 12 weeks | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | Baseline | Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning.Baseline is the mean of last 10 days of data before start of treatment |
| PEF - End-value Measured by Patient at Home (L/Min) in the Morning | Last 6 weeks on treatment | Peak Expiratory Flow (L/min) |
| FEV1 - Baseline Measured by Patient at Home (L) in the Morning | Baseline | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning.Baseline is the mean of last 10 days of data before start of treatment |
| FEV1 - End-value Measured by Patient at Home (L) in the Morning | Last 6 weeks on treatment | Forced Expiratory Volume in 1 second (L) |
| Post-bronchodilator FEV1 (L) - Baseline | Day 1 | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic |
| EXACT - End-value Total Score | Measured daily in the evening for 12 weeks | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status)scale). Last 6 weeks on treatment. |
| BCSS - Baseline Total Score | Baseline | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status)scale).Baseline is the mean of last 10 days of data before start of treatment |
| BCSS - End-value Total Score | Measured daily in the evening for 12 weeks | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0(best health status) to 12(worst possible status)scale). Last 6 weeks on treatment |
| Sputum Colour - Baseline | Baseline | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). |
| Sputum Colour - End Value | Measured at clinic visits:1, 4, 8 and 12 weeks | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status).End of treatment week 12 |
| Use of Reliever Medication | Last 6 weeks on treatment | Daily average of number of inhalations of reliever medication |
| Six-minute Walk Test - Distance Walked at Baseline (m) | Day 1 | — |
| Six-minute Walk Test - End-value Distance Walked (m) | Measured Day 1 and 12 weeks | distance walked on vist 6 - last on treatment clinic visit |
| Exacerbations - Clinic Defined | Duration of the the treatment period - 12 weeks | Number of patients having a clinic defined disease exacerbation |
| St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | Day 1 | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a % scale from 0 (best health status) to 100(worst possible status)). |
| St George's Respiratory Questionnaire (COPD) - End-value Overall Score | Measured Day 1 and 12 weeks | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a % scale from 0 (best health status) to 100(worst possible status)).questionaire assessed on vist 6 -( last on treatment clinic visit) |
| EXACT - Baseline Total Score | Baseline | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status)scale). Baseline is the mean of last 10 days of data before start of treatment. |
| Post-bronchodilator FEV1 (L) - End-value | Measured at clinic visits: 1, 4, 8 and 12 weeks | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
Countries
Australia, Canada, Germany, Japan, Philippines, Poland, Russia, Slovakia, South Korea, Taiwan, Ukraine, United States
Participant flow
Recruitment details
First patient enrolled 13 July 2009. Last patient completed 05 August 2010. Study conducted at 138 centres in 12 countries (Australia, Canada, Germany, Japan, Korea, Philippines, Poland, Russia, Slovakia, Taiwan, Ukraine and US)
Pre-assignment details
Patients were stabilised on maintenance therapy (tiotropium, 18 micrograms od) during a 2-week run-in period before randomisation.
Participants by arm
| Arm | Count |
|---|---|
| 5 mg AZD9668 AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks | 212 |
| 20 mg AZD9668 AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks | 206 |
| 60 mg AZD9668 AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks | 202 |
| Placebo Matched Placebo Tablets | 218 |
| Total | 838 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 11 | 10 | 10 |
| Overall Study | Incorrect enrolment | 5 | 10 | 4 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 3 |
| Overall Study | Other | 1 | 0 | 0 | 0 |
| Overall Study | Safety reason | 0 | 1 | 0 | 0 |
| Overall Study | Severe non-compliance | 3 | 1 | 0 | 2 |
| Overall Study | Study-specific criteria | 0 | 1 | 1 | 0 |
| Overall Study | Voluntary discontinuation | 6 | 5 | 3 | 6 |
Baseline characteristics
| Characteristic | 5 mg AZD9668 | 20 mg AZD9668 | 60 mg AZD9668 | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 62 Years | 63 Years | 61 Years | 62 Years | 62 Years |
| Sex: Female, Male Female | 46 Participants | 47 Participants | 53 Participants | 53 Participants | 199 Participants |
| Sex: Female, Male Male | 166 Participants | 159 Participants | 149 Participants | 165 Participants | 639 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 212 | 14 / 206 | 13 / 202 | 24 / 218 |
| serious Total, serious adverse events | 7 / 212 | 14 / 206 | 15 / 202 | 9 / 218 |
Outcome results
Primary
Baseline Pre-bronchodilator FEV1 (L)
Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Baseline Pre-bronchodilator FEV1 (L) | 1.51 L | Standard Deviation 0.471 |
| 20 mg AZD9668 | Baseline Pre-bronchodilator FEV1 (L) | 1.47 L | Standard Deviation 0.468 |
| 60 mg AZD9668 | Baseline Pre-bronchodilator FEV1 (L) | 1.50 L | Standard Deviation 0.512 |
| Placebo | Baseline Pre-bronchodilator FEV1 (L) | 1.51 L | Standard Deviation 0.467 |
Primary
End-value Pre-bronchodilator FEV1 (L)
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: Measured at clinic visits: 1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | End-value Pre-bronchodilator FEV1 (L) | 1.51 L | Standard Error 0.018 |
| 20 mg AZD9668 | End-value Pre-bronchodilator FEV1 (L) | 1.47 L | Standard Error 0.018 |
| 60 mg AZD9668 | End-value Pre-bronchodilator FEV1 (L) | 1.46 L | Standard Error 0.018 |
| Placebo | End-value Pre-bronchodilator FEV1 (L) | 1.47 L | Standard Error 0.018 |
Secondary
BCSS - Baseline Total Score
Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status)scale).Baseline is the mean of last 10 days of data before start of treatment
Time frame: Baseline
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | BCSS - Baseline Total Score | 4.85 Units on a scale | Standard Deviation 1.954 |
| 20 mg AZD9668 | BCSS - Baseline Total Score | 4.66 Units on a scale | Standard Deviation 1.526 |
| 60 mg AZD9668 | BCSS - Baseline Total Score | 4.79 Units on a scale | Standard Deviation 1.756 |
| Placebo | BCSS - Baseline Total Score | 4.48 Units on a scale | Standard Deviation 1.782 |
Secondary
BCSS - End-value Total Score
Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0(best health status) to 12(worst possible status)scale). Last 6 weeks on treatment
Time frame: Measured daily in the evening for 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | BCSS - End-value Total Score | 4.09 Units on a scale | Standard Error 0.098 |
| 20 mg AZD9668 | BCSS - End-value Total Score | 4.03 Units on a scale | Standard Error 0.099 |
| 60 mg AZD9668 | BCSS - End-value Total Score | 4.25 Units on a scale | Standard Error 0.1 |
| Placebo | BCSS - End-value Total Score | 4.20 Units on a scale | Standard Error 0.096 |
Secondary
Exacerbations - Clinic Defined
Number of patients having a clinic defined disease exacerbation
Time frame: Duration of the the treatment period - 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg AZD9668 | Exacerbations - Clinic Defined | 29 Participants |
| 20 mg AZD9668 | Exacerbations - Clinic Defined | 28 Participants |
| 60 mg AZD9668 | Exacerbations - Clinic Defined | 34 Participants |
| Placebo | Exacerbations - Clinic Defined | 29 Participants |
Secondary
EXACT - Baseline Total Score
EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status)scale). Baseline is the mean of last 10 days of data before start of treatment.
Time frame: Baseline
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | EXACT - Baseline Total Score | 43.17 Units on a scale | Standard Deviation 10.109 |
| 20 mg AZD9668 | EXACT - Baseline Total Score | 42.38 Units on a scale | Standard Deviation 8.166 |
| 60 mg AZD9668 | EXACT - Baseline Total Score | 42.37 Units on a scale | Standard Deviation 9.32 |
| Placebo | EXACT - Baseline Total Score | 40.95 Units on a scale | Standard Deviation 9.725 |
Secondary
EXACT - End-value Total Score
EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status)scale). Last 6 weeks on treatment.
Time frame: Measured daily in the evening for 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | EXACT - End-value Total Score | 39.97 Units on a scale | Standard Error 0.545 |
| 20 mg AZD9668 | EXACT - End-value Total Score | 39.72 Units on a scale | Standard Error 0.543 |
| 60 mg AZD9668 | EXACT - End-value Total Score | 40.59 Units on a scale | Standard Error 0.552 |
| Placebo | EXACT - End-value Total Score | 39.71 Units on a scale | Standard Error 0.533 |
Secondary
FEV1 - Baseline Measured by Patient at Home (L) in the Morning
Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning.Baseline is the mean of last 10 days of data before start of treatment
Time frame: Baseline
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | FEV1 - Baseline Measured by Patient at Home (L) in the Morning | 1.40 L | Standard Deviation 0.521 |
| 20 mg AZD9668 | FEV1 - Baseline Measured by Patient at Home (L) in the Morning | 1.34 L | Standard Deviation 0.444 |
| 60 mg AZD9668 | FEV1 - Baseline Measured by Patient at Home (L) in the Morning | 1.36 L | Standard Deviation 0.507 |
| Placebo | FEV1 - Baseline Measured by Patient at Home (L) in the Morning | 1.38 L | Standard Deviation 0.456 |
Secondary
FEV1 - End-value Measured by Patient at Home (L) in the Morning
Forced Expiratory Volume in 1 second (L)
Time frame: Last 6 weeks on treatment
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | FEV1 - End-value Measured by Patient at Home (L) in the Morning | 1.36 L | Standard Error 0.018 |
| 20 mg AZD9668 | FEV1 - End-value Measured by Patient at Home (L) in the Morning | 1.35 L | Standard Error 0.018 |
| 60 mg AZD9668 | FEV1 - End-value Measured by Patient at Home (L) in the Morning | 1.33 L | Standard Error 0.018 |
| Placebo | FEV1 - End-value Measured by Patient at Home (L) in the Morning | 1.34 L | Standard Error 0.018 |
Secondary
PEF - Baseline Measured by Patient at Home (L/Min) in the Morning
Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning.Baseline is the mean of last 10 days of data before start of treatment
Time frame: Baseline
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | 222.33 L/min | Standard Deviation 83.177 |
| 20 mg AZD9668 | PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | 219.86 L/min | Standard Deviation 90.395 |
| 60 mg AZD9668 | PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | 216.99 L/min | Standard Deviation 91.299 |
| Placebo | PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | 221.79 L/min | Standard Deviation 89.005 |
Secondary
PEF - End-value Measured by Patient at Home (L/Min) in the Morning
Peak Expiratory Flow (L/min)
Time frame: Last 6 weeks on treatment
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | PEF - End-value Measured by Patient at Home (L/Min) in the Morning | 214.30 L/min | Standard Error 2.899 |
| 20 mg AZD9668 | PEF - End-value Measured by Patient at Home (L/Min) in the Morning | 214.55 L/min | Standard Error 2.92 |
| 60 mg AZD9668 | PEF - End-value Measured by Patient at Home (L/Min) in the Morning | 212.35 L/min | Standard Error 2.944 |
| Placebo | PEF - End-value Measured by Patient at Home (L/Min) in the Morning | 220.47 L/min | Standard Error 2.84 |
Secondary
Post-bronchodilator FEV1 (L) - Baseline
Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Post-bronchodilator FEV1 (L) - Baseline | 1.68 L | Standard Deviation 0.501 |
| 20 mg AZD9668 | Post-bronchodilator FEV1 (L) - Baseline | 1.64 L | Standard Deviation 0.472 |
| 60 mg AZD9668 | Post-bronchodilator FEV1 (L) - Baseline | 1.65 L | Standard Deviation 0.516 |
| Placebo | Post-bronchodilator FEV1 (L) - Baseline | 1.69 L | Standard Deviation 0.471 |
Secondary
Post-bronchodilator FEV1 (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: Measured at clinic visits: 1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Post-bronchodilator FEV1 (L) - End-value | 1.66 L | Standard Error 0.017 |
| 20 mg AZD9668 | Post-bronchodilator FEV1 (L) - End-value | 1.63 L | Standard Error 0.017 |
| 60 mg AZD9668 | Post-bronchodilator FEV1 (L) - End-value | 1.63 L | Standard Error 0.017 |
| Placebo | Post-bronchodilator FEV1 (L) - End-value | 1.62 L | Standard Error 0.017 |
Secondary
Post-bronchodilator FVC (L) - Baseline
Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Post-bronchodilator FVC (L) - Baseline | 3.30 L | Standard Deviation 0.914 |
| 20 mg AZD9668 | Post-bronchodilator FVC (L) - Baseline | 3.24 L | Standard Deviation 0.723 |
| 60 mg AZD9668 | Post-bronchodilator FVC (L) - Baseline | 3.24 L | Standard Deviation 0.885 |
| Placebo | Post-bronchodilator FVC (L) - Baseline | 3.27 L | Standard Deviation 0.781 |
Secondary
Post-bronchodilator FVC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: Measured at clinic visits: 1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Post-bronchodilator FVC (L) - End-value | 3.28 L | Standard Error 0.023 |
| 20 mg AZD9668 | Post-bronchodilator FVC (L) - End-value | 3.26 L | Standard Error 0.024 |
| 60 mg AZD9668 | Post-bronchodilator FVC (L) - End-value | 3.24 L | Standard Error 0.024 |
| Placebo | Post-bronchodilator FVC (L) - End-value | 3.22 L | Standard Error 0.023 |
Secondary
Post-bronchodilator IC (L) - Baseline
Inspiratory Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Post-bronchodilator IC (L) - Baseline | 2.37 L | Standard Deviation 0.709 |
| 20 mg AZD9668 | Post-bronchodilator IC (L) - Baseline | 2.30 L | Standard Deviation 0.601 |
| 60 mg AZD9668 | Post-bronchodilator IC (L) - Baseline | 2.28 L | Standard Deviation 0.677 |
| Placebo | Post-bronchodilator IC (L) - Baseline | 2.32 L | Standard Deviation 0.628 |
Secondary
Post-bronchodilator IC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: Measured at clinic visits: 1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Post-bronchodilator IC (L) - End-value | 2.29 L | Standard Error 0.025 |
| 20 mg AZD9668 | Post-bronchodilator IC (L) - End-value | 2.30 L | Standard Error 0.025 |
| 60 mg AZD9668 | Post-bronchodilator IC (L) - End-value | 2.31 L | Standard Error 0.025 |
| Placebo | Post-bronchodilator IC (L) - End-value | 2.30 L | Standard Error 0.025 |
Secondary
Pre-bronchodilator FVC (L) - Baseline
Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Pre-bronchodilator FVC (L) - Baseline | 3.08 L | Standard Deviation 0.85 |
| 20 mg AZD9668 | Pre-bronchodilator FVC (L) - Baseline | 3.01 L | Standard Deviation 0.739 |
| 60 mg AZD9668 | Pre-bronchodilator FVC (L) - Baseline | 3.06 L | Standard Deviation 0.856 |
| Placebo | Pre-bronchodilator FVC (L) - Baseline | 3.04 L | Standard Deviation 0.754 |
Secondary
Pre-bronchodilator FVC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: Measured at clinic visits: 1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Pre-bronchodilator FVC (L) - End-value | 3.08 L | Standard Error 0.026 |
| 20 mg AZD9668 | Pre-bronchodilator FVC (L) - End-value | 3.05 L | Standard Error 0.026 |
| 60 mg AZD9668 | Pre-bronchodilator FVC (L) - End-value | 3.02 L | Standard Error 0.026 |
| Placebo | Pre-bronchodilator FVC (L) - End-value | 3.02 L | Standard Error 0.025 |
Secondary
Pre-bronchodilator IC (L) - Baseline
Inspiratory Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Pre-bronchodilator IC (L) - Baseline | 2.22 L | Standard Deviation 0.68 |
| 20 mg AZD9668 | Pre-bronchodilator IC (L) - Baseline | 2.14 L | Standard Deviation 0.563 |
| 60 mg AZD9668 | Pre-bronchodilator IC (L) - Baseline | 2.15 L | Standard Deviation 0.662 |
| Placebo | Pre-bronchodilator IC (L) - Baseline | 2.17 L | Standard Deviation 0.574 |
Secondary
Pre-bronchodilator IC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: Measured at clinic visits: 1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Pre-bronchodilator IC (L) - End-value | 2.15 L | Standard Error 0.027 |
| 20 mg AZD9668 | Pre-bronchodilator IC (L) - End-value | 2.15 L | Standard Error 0.028 |
| 60 mg AZD9668 | Pre-bronchodilator IC (L) - End-value | 2.16 L | Standard Error 0.027 |
| Placebo | Pre-bronchodilator IC (L) - End-value | 2.15 L | Standard Error 0.026 |
Secondary
Six-minute Walk Test - Distance Walked at Baseline (m)
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Six-minute Walk Test - Distance Walked at Baseline (m) | 386.2 m | Standard Deviation 125.22 |
| 20 mg AZD9668 | Six-minute Walk Test - Distance Walked at Baseline (m) | 402.2 m | Standard Deviation 111.98 |
| 60 mg AZD9668 | Six-minute Walk Test - Distance Walked at Baseline (m) | 384.9 m | Standard Deviation 115.5 |
| Placebo | Six-minute Walk Test - Distance Walked at Baseline (m) | 386.0 m | Standard Deviation 132.48 |
Secondary
Six-minute Walk Test - End-value Distance Walked (m)
distance walked on vist 6 - last on treatment clinic visit
Time frame: Measured Day 1 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Six-minute Walk Test - End-value Distance Walked (m) | 396.7 m | Standard Error 4.74 |
| 20 mg AZD9668 | Six-minute Walk Test - End-value Distance Walked (m) | 397.8 m | Standard Error 4.87 |
| 60 mg AZD9668 | Six-minute Walk Test - End-value Distance Walked (m) | 411.2 m | Standard Error 4.76 |
| Placebo | Six-minute Walk Test - End-value Distance Walked (m) | 409.5 m | Standard Error 4.61 |
Secondary
Sputum Colour - Baseline
Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status).
Time frame: Baseline
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Sputum Colour - Baseline | 2.15 Units on a scale | Standard Deviation 1.069 |
| 20 mg AZD9668 | Sputum Colour - Baseline | 2.34 Units on a scale | Standard Deviation 1.137 |
| 60 mg AZD9668 | Sputum Colour - Baseline | 2.13 Units on a scale | Standard Deviation 0.956 |
| Placebo | Sputum Colour - Baseline | 2.16 Units on a scale | Standard Deviation 1.046 |
Secondary
Sputum Colour - End Value
Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status).End of treatment week 12
Time frame: Measured at clinic visits:1, 4, 8 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Sputum Colour - End Value | 2.11 Units on a scale | Standard Error 0.062 |
| 20 mg AZD9668 | Sputum Colour - End Value | 2.03 Units on a scale | Standard Error 0.065 |
| 60 mg AZD9668 | Sputum Colour - End Value | 2.20 Units on a scale | Standard Error 0.063 |
| Placebo | Sputum Colour - End Value | 2.11 Units on a scale | Standard Error 0.062 |
Secondary
St George's Respiratory Questionnaire (COPD) - End-value Overall Score
St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a % scale from 0 (best health status) to 100(worst possible status)).questionaire assessed on vist 6 -( last on treatment clinic visit)
Time frame: Measured Day 1 and 12 weeks
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - End-value Overall Score | 49.50 Scores on a scale | Standard Error 1.014 |
| 20 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - End-value Overall Score | 49.49 Scores on a scale | Standard Error 1.049 |
| 60 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - End-value Overall Score | 47.93 Scores on a scale | Standard Error 1.023 |
| Placebo | St George's Respiratory Questionnaire (COPD) - End-value Overall Score | 46.35 Scores on a scale | Standard Error 0.984 |
Secondary
St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline
St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a % scale from 0 (best health status) to 100(worst possible status)).
Time frame: Day 1
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 53.98 Scores on a scale | Standard Deviation 18.276 |
| 20 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 51.98 Scores on a scale | Standard Deviation 18.207 |
| 60 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 52.97 Scores on a scale | Standard Deviation 18.234 |
| Placebo | St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 51.41 Scores on a scale | Standard Deviation 18.849 |
Secondary
Use of Reliever Medication
Daily average of number of inhalations of reliever medication
Time frame: Last 6 weeks on treatment
Population: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg AZD9668 | Use of Reliever Medication | 4.28 Inhalations | Standard Error 0.173 |
| 20 mg AZD9668 | Use of Reliever Medication | 4.20 Inhalations | Standard Error 0.175 |
| 60 mg AZD9668 | Use of Reliever Medication | 4.65 Inhalations | Standard Error 0.175 |
| Placebo | Use of Reliever Medication | 4.56 Inhalations | Standard Error 0.17 |