Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic, obstructive, pulmonary, lung, respiratory disease, efficacy, placebo-controlled, COPD, FEV1, St Georges Respiratory Questionnaire
Brief summary
The primary objective is to evaluate the efficacy of AZD9668 compared with placebo in symptomatic COPD patients by assessing the effects on lung function and symptoms of COPD
Interventions
DRUGAZD9668
2 x 30 mg oral tablets bd for 12 weeks
DRUGPlacebo
2 x matched placebo to oral tablet bd for 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 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of COPD with symptoms over 1 year * FEV1/FVC \< 70% and FEV1 \>= 30 and \< 80 % of predicted post-bronchodilator * Symptomatic COPD for a total of 7 days in the two weeks prior to randomisation * At least 1 COPD exacerbation from 4 weeks to 12 months before the screening visit
Exclusion criteria
* Past history or current evidence of clinically significant heart disease * Current diagnosis of asthma * Patients who require long term oxygen therapy * Worsening of COPD requiring treatment with antibiotics, an increase in inhaled steroid dose and/or oral steroids 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 (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. |
| End-value Pre-bronchodilator FEV1 (L) | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PEF - End-value Measured by Patient at Home (L/Min) in the Morning | Last 6 weeks on treatment | Peak expiratory flow (PEF) |
| Post-bronchodilator FEV1 (L) - Baseline | Day 1 | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. |
| Post-bronchodilator FEV1 (L) - End-value | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Pre-bronchodilator FVC (L) - Baseline | Day 1 | Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. |
| Pre-bronchodilator FVC (L) - End-value | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Post-bronchodilator FVC (L) - Baseline | Day 1 | Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. |
| Post-bronchodilator FVC (L) - End-value | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Baseline Pre-bronchodilator FEV6 (L) | Day 1 | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. |
| End-value Pre-bronchodilator FEV6 (L) | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Baseline Post-bronchodilator FEV6 (L) | Day 1 | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post after bronchodilator (salbutamol) use in the clinic. |
| End-value Post-bronchodilator FEV6 (L) | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Baseline Pre-bronchodilator FEF25-75% (L/Sec) | Day 1 | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. |
| End-value Pre-bronchodilator FEF25-75% (L/Sec) | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Baseline Post-bronchodilator FEF25-75% (L/Sec) | Day 1 | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. |
| End-value Post-bronchodilator FEF25-75% (L/Sec) | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Pre-bronchodilator IC (L) - Baseline | Day 1 | Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. |
| Pre-bronchodilator IC (L) - End-value | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| Post-bronchodilator IC (L) - End-value | up to week 12 | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) |
| 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) |
| 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. |
| EXACT - End-value Total Score | Last 6 weeks on treatment | 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). |
| 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 | Last 6 weeks on treatment | 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). |
| 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 | End of treatment week 12 | 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 |
| Incremental Shuttle Walk Test - Baseline | Day 1 | Endurance time (s) |
| Incremental Shuttle Walk Test - End Value | Week 12 - visit 6 | — |
| Endurance Shuttle Walk Test - Baseline | Day 1 | Endurance time (s) |
| Endurance Shuttle Walk Test - End Value | Week 12 - visit 6 | Assessed at vist 6 -( last on treatment clinic visit) |
| 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) |
| Exacerbations - Clinic Defined | Duration of the the treatment period - 12 weeks | Number of patients having a clinic defined disease exacerbation. |
| Post-bronchodilator IC (L) - Baseline | Day 1 | Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. |
| 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. |
Countries
Bulgaria, Czechia, Hungary, Poland, Romania, Slovakia
Participant flow
Recruitment details
First patient enrolled 24 November 2009. Last patient completed 18 August 2010. Study conducted at 79 centres in 6 countries (Bulgaria, Czech Republic, Hungary, Poland, Romania, Slovakia).
Pre-assignment details
3- or 4-week run-in period on budesonide/formoterol twice daily to stabilise patients on maintenance therapy before randomisation. Patients already on budesonide/formoterol required a 3-week run-in period and patients on ICS as monotherapy or in combination with any long-acting bronchodilator required a 4-week run-in period.
Participants by arm
| Arm | Count |
|---|---|
| 60 mg AZD9668 AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks | 313 |
| Placebo Matched Placebo Tablets | 302 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 6 |
| Overall Study | Incorrect enrolment | 4 | 2 |
| Overall Study | Safety reason | 0 | 3 |
| Overall Study | Study-specific criteria | 4 | 2 |
| Overall Study | Voluntary discontinuation | 7 | 5 |
Baseline characteristics
| Characteristic | 60 mg AZD9668 | Placebo | Total |
|---|---|---|---|
| Age Continuous | 62 Years | 61 Years | 61.5 Years |
| Sex: Female, Male Female | 80 Participants | 81 Participants | 161 Participants |
| Sex: Female, Male Male | 233 Participants | 221 Participants | 454 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 313 | 0 / 302 |
| serious Total, serious adverse events | 9 / 313 | 14 / 302 |
Outcome results
Primary
Baseline Pre-bronchodilator FEV1 (L)
Forced expiratory volume in 1 second (FEV1) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Baseline Pre-bronchodilator FEV1 (L) | 1.49 L | Standard Deviation 0.539 |
| Placebo | Baseline Pre-bronchodilator FEV1 (L) | 1.44 L | Standard Deviation 0.519 |
Primary
End-value Pre-bronchodilator FEV1 (L)
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | End-value Pre-bronchodilator FEV1 (L) | 1.45 L | Standard Error 0.015 |
| Placebo | End-value Pre-bronchodilator FEV1 (L) | 1.43 L | Standard Error 0.015 |
Secondary
Baseline Post-bronchodilator FEF25-75% (L/Sec)
Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Baseline Post-bronchodilator FEF25-75% (L/Sec) | 0.64 L/sec | Standard Deviation 0.367 |
| Placebo | Baseline Post-bronchodilator FEF25-75% (L/Sec) | 0.60 L/sec | Standard Deviation 0.333 |
Secondary
Baseline Post-bronchodilator FEV6 (L)
Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post 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 |
|---|---|---|---|
| 60 mg AZD9668 | Baseline Post-bronchodilator FEV6 (L) | 2.85 L | Standard Deviation 0.724 |
| Placebo | Baseline Post-bronchodilator FEV6 (L) | 2.79 L | Standard Deviation 0.716 |
Secondary
Baseline Pre-bronchodilator FEF25-75% (L/Sec)
Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Baseline Pre-bronchodilator FEF25-75% (L/Sec) | 0.60 L/sec | Standard Deviation 0.38 |
| Placebo | Baseline Pre-bronchodilator FEF25-75% (L/Sec) | 0.55 L/sec | Standard Deviation 0.324 |
Secondary
Baseline Pre-bronchodilator FEV6 (L)
Forced expiratory volume in 6 seconds (FEV6) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Baseline Pre-bronchodilator FEV6 (L) | 2.68 L | Standard Deviation 0.729 |
| Placebo | Baseline Pre-bronchodilator FEV6 (L) | 2.61 L | Standard Deviation 0.714 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | BCSS - Baseline Total Score | 5.26 units on a scale | Standard Deviation 1.787 |
| Placebo | BCSS - Baseline Total Score | 5.44 units on a scale | Standard Deviation 1.765 |
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).
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 |
|---|---|---|---|
| 60 mg AZD9668 | BCSS - End-value Total Score | 4.68 units on a scale | Standard Error 0.085 |
| Placebo | BCSS - End-value Total Score | 4.68 units on a scale | Standard Error 0.086 |
Secondary
Endurance Shuttle Walk Test - Baseline
Endurance time (s)
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 |
|---|---|---|---|
| 60 mg AZD9668 | Endurance Shuttle Walk Test - Baseline | 419 seconds | Standard Deviation 269.4 |
| Placebo | Endurance Shuttle Walk Test - Baseline | 449 seconds | Standard Deviation 292.9 |
Secondary
Endurance Shuttle Walk Test - End Value
Assessed at vist 6 -( last on treatment clinic visit)
Time frame: Week 12 - visit 6
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 |
|---|---|---|---|
| 60 mg AZD9668 | Endurance Shuttle Walk Test - End Value | 449.6 seconds | Standard Error 10.49 |
| Placebo | Endurance Shuttle Walk Test - End Value | 459.9 seconds | Standard Error 10.68 |
Secondary
End-value Post-bronchodilator FEF25-75% (L/Sec)
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | End-value Post-bronchodilator FEF25-75% (L/Sec) | 0.62 L/sec | Standard Error 0.016 |
| Placebo | End-value Post-bronchodilator FEF25-75% (L/Sec) | 0.61 L/sec | Standard Error 0.016 |
Secondary
End-value Post-bronchodilator FEV6 (L)
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | End-value Post-bronchodilator FEV6 (L) | 2.77 L | Standard Error 0.017 |
| Placebo | End-value Post-bronchodilator FEV6 (L) | 2.78 L | Standard Error 0.018 |
Secondary
End-value Pre-bronchodilator FEF25-75% (L/Sec)
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | End-value Pre-bronchodilator FEF25-75% (L/Sec) | 0.57 L/sec | Standard Error 0.016 |
| Placebo | End-value Pre-bronchodilator FEF25-75% (L/Sec) | 0.56 L/sec | Standard Error 0.016 |
Secondary
End-value Pre-bronchodilator FEV6 (L)
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | End-value Pre-bronchodilator FEV6 (L) | 2.61 L | Standard Error 0.019 |
| Placebo | End-value Pre-bronchodilator FEV6 (L) | 2.61 L | Standard Error 0.019 |
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) |
|---|---|---|
| 60 mg AZD9668 | Exacerbations - Clinic Defined | 22 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 |
|---|---|---|---|
| 60 mg AZD9668 | EXACT - Baseline Total Score | 45.47 units on a scale | Standard Deviation 9.683 |
| Placebo | EXACT - Baseline Total Score | 46.01 units on a scale | Standard Deviation 8.9 |
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).
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 |
|---|---|---|---|
| 60 mg AZD9668 | EXACT - End-value Total Score | 42.78 units on a scale | Standard Error 0.473 |
| Placebo | EXACT - End-value Total Score | 43.07 units on a scale | Standard Error 0.48 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | FEV1 - Baseline Measured by Patient at Home (L) in the Morning | 1.40 L | Standard Deviation 0.546 |
| Placebo | FEV1 - Baseline Measured by Patient at Home (L) in the Morning | 1.34 L | Standard Deviation 0.516 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | FEV1 - End-value Measured by Patient at Home (L) in the Morning | 1.32 L | Standard Error 0.012 |
| Placebo | FEV1 - End-value Measured by Patient at Home (L) in the Morning | 1.32 L | Standard Error 0.012 |
Secondary
Incremental Shuttle Walk Test - Baseline
Endurance time (s)
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 |
|---|---|---|---|
| 60 mg AZD9668 | Incremental Shuttle Walk Test - Baseline | 351 seconds | Standard Deviation 119.5 |
| Placebo | Incremental Shuttle Walk Test - Baseline | 352 seconds | Standard Deviation 108.3 |
Secondary
Incremental Shuttle Walk Test - End Value
Time frame: Week 12 - visit 6
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 |
|---|---|---|---|
| 60 mg AZD9668 | Incremental Shuttle Walk Test - End Value | 363.6 seconds | Standard Error 3.39 |
| Placebo | Incremental Shuttle Walk Test - End Value | 363.7 seconds | Standard Error 3.44 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | 215.60 L/min | Standard Deviation 98.406 |
| Placebo | PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | 213.24 L/min | Standard Deviation 96.803 |
Secondary
PEF - End-value Measured by Patient at Home (L/Min) in the Morning
Peak expiratory flow (PEF)
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 |
|---|---|---|---|
| 60 mg AZD9668 | PEF - End-value Measured by Patient at Home (L/Min) in the Morning | 208.68 L/min | Standard Error 2.153 |
| Placebo | PEF - End-value Measured by Patient at Home (L/Min) in the Morning | 211.93 L/min | Standard Error 2.189 |
Secondary
Post-bronchodilator FEV1 (L) - Baseline
Forced expiratory volume in 1 second (FEV1) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Post-bronchodilator FEV1 (L) - Baseline | 1.59 L | Standard Deviation 0.53 |
| Placebo | Post-bronchodilator FEV1 (L) - Baseline | 1.56 L | Standard Deviation 0.518 |
Secondary
Post-bronchodilator FEV1 (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | Post-bronchodilator FEV1 (L) - End-value | 1.56 L | Standard Error 0.014 |
| Placebo | Post-bronchodilator FEV1 (L) - End-value | 1.54 L | Standard Error 0.015 |
Secondary
Post-bronchodilator FVC (L) - Baseline
Forced vital capacity (FVC) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Post-bronchodilator FVC (L) - Baseline | 3.16 L | Standard Deviation 0.787 |
| Placebo | Post-bronchodilator FVC (L) - Baseline | 3.12 L | Standard Deviation 0.822 |
Secondary
Post-bronchodilator FVC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | Post-bronchodilator FVC (L) - End-value | 3.11 L | Standard Error 0.021 |
| Placebo | Post-bronchodilator FVC (L) - End-value | 3.11 L | Standard Error 0.021 |
Secondary
Post-bronchodilator IC (L) - Baseline
Inspiratory capacity (IC) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Post-bronchodilator IC (L) - Baseline | 2.33 L | Standard Deviation 0.718 |
| Placebo | Post-bronchodilator IC (L) - Baseline | 2.30 L | Standard Deviation 0.665 |
Secondary
Post-bronchodilator IC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | Post-bronchodilator IC (L) - End-value | 2.30 L | Standard Error 0.023 |
| Placebo | Post-bronchodilator IC (L) - End-value | 2.27 L | Standard Error 0.023 |
Secondary
Pre-bronchodilator FVC (L) - Baseline
Forced vital capacity (FVC) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Pre-bronchodilator FVC (L) - Baseline | 2.98 L | Standard Deviation 0.781 |
| Placebo | Pre-bronchodilator FVC (L) - Baseline | 2.94 L | Standard Deviation 0.806 |
Secondary
Pre-bronchodilator FVC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | Pre-bronchodilator FVC (L) - End-value | 2.94 L | Standard Error 0.022 |
| Placebo | Pre-bronchodilator FVC (L) - End-value | 2.93 L | Standard Error 0.022 |
Secondary
Pre-bronchodilator IC (L) - Baseline
Inspiratory capacity (IC) 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 |
|---|---|---|---|
| 60 mg AZD9668 | Pre-bronchodilator IC (L) - Baseline | 2.21 L | Standard Deviation 0.661 |
| Placebo | Pre-bronchodilator IC (L) - Baseline | 2.17 L | Standard Deviation 0.661 |
Secondary
Pre-bronchodilator IC (L) - End-value
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time frame: up to week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | Pre-bronchodilator IC (L) - End-value | 2.13 L | Standard Error 0.024 |
| Placebo | Pre-bronchodilator IC (L) - End-value | 2.14 L | Standard Error 0.025 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | Sputum Colour - Baseline | 1.87 units on a scale | Standard Deviation 0.901 |
| Placebo | Sputum Colour - Baseline | 1.88 units on a scale | Standard Deviation 0.807 |
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: End of treatment week 12
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 |
|---|---|---|---|
| 60 mg AZD9668 | Sputum Colour - End Value | 1.63 units on a scale | Standard Error 0.042 |
| Placebo | Sputum Colour - End Value | 1.70 units on a scale | Standard Error 0.042 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - End-value Overall Score | 49.89 Scores on a scale | Standard Error 0.777 |
| Placebo | St George's Respiratory Questionnaire (COPD) - End-value Overall Score | 50.66 Scores on a scale | Standard Error 0.796 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 54.52 Scores on a scale | Standard Deviation 16.863 |
| Placebo | St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 54.87 Scores on a scale | Standard Deviation 17.575 |
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 |
|---|---|---|---|
| 60 mg AZD9668 | Use of Reliever Medication | 3.40 inhalations | Standard Error 0.124 |
| Placebo | Use of Reliever Medication | 3.37 inhalations | Standard Error 0.126 |