Trial Outcomes & Findings for A Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at Three Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium (NCT NCT00949975)
NCT ID: NCT00949975
Last Updated: 2012-08-03
Results Overview
Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
COMPLETED
PHASE2
838 participants
Day 1
2012-08-03
Participant Flow
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)
Patients were stabilised on maintenance therapy (tiotropium, 18 micrograms od) during a 2-week run-in period before randomisation.
Participant milestones
| Measure |
5 mg AZD9668
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
212
|
206
|
202
|
218
|
|
Overall Study
COMPLETED
|
185
|
177
|
183
|
190
|
|
Overall Study
NOT COMPLETED
|
27
|
29
|
19
|
28
|
Reasons for withdrawal
| Measure |
5 mg AZD9668
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Overall Study
Voluntary discontinuation
|
6
|
5
|
3
|
6
|
|
Overall Study
Adverse Event
|
11
|
11
|
10
|
10
|
|
Overall Study
Safety reason
|
0
|
1
|
0
|
0
|
|
Overall Study
Study-specific criteria
|
0
|
1
|
1
|
0
|
|
Overall Study
Incorrect enrolment
|
5
|
10
|
4
|
7
|
|
Overall Study
Severe non-compliance
|
3
|
1
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
1
|
3
|
|
Overall Study
Other
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at Three Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium
Baseline characteristics by cohort
| Measure |
5 mg AZD9668
n=212 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=206 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=218 Participants
Matched Placebo Tablets
|
Total
n=838 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
62 Years
n=5 Participants
|
63 Years
n=7 Participants
|
61 Years
n=5 Participants
|
62 Years
n=4 Participants
|
62 Years
n=21 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
199 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
166 Participants
n=5 Participants
|
159 Participants
n=7 Participants
|
149 Participants
n=5 Participants
|
165 Participants
n=4 Participants
|
639 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: 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.
Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=216 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Baseline Pre-bronchodilator FEV1 (L)
|
1.51 L
Standard Deviation 0.471
|
1.47 L
Standard Deviation 0.468
|
1.50 L
Standard Deviation 0.512
|
1.51 L
Standard Deviation 0.467
|
PRIMARY outcome
Timeframe: Measured at clinic visits: 1, 4, 8 and 12 weeksPopulation: 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.
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=216 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
End-value Pre-bronchodilator FEV1 (L)
|
1.51 L
Standard Error 0.018 • Interval 0.018 to
|
1.47 L
Standard Error 0.018 • Interval 0.018 to
|
1.46 L
Standard Error 0.018 • Interval 0.018 to
|
1.47 L
Standard Error 0.018 • Interval 0.018 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic
Outcome measures
| Measure |
5 mg AZD9668
n=207 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=215 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Post-bronchodilator FEV1 (L) - Baseline
|
1.68 L
Standard Deviation 0.501
|
1.64 L
Standard Deviation 0.472
|
1.65 L
Standard Deviation 0.516
|
1.69 L
Standard Deviation 0.471
|
SECONDARY outcome
Timeframe: Measured at clinic visits: 1, 4, 8 and 12 weeksPopulation: 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.
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Outcome measures
| Measure |
5 mg AZD9668
n=207 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=215 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Post-bronchodilator FEV1 (L) - End-value
|
1.66 L
Standard Error 0.017 • Interval 0.017 to
|
1.63 L
Standard Error 0.017 • Interval 0.017 to
|
1.63 L
Standard Error 0.017 • Interval 0.017 to
|
1.62 L
Standard Error 0.017 • Interval 0.017 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=216 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Pre-bronchodilator FVC (L) - Baseline
|
3.08 L
Standard Deviation 0.850
|
3.01 L
Standard Deviation 0.739
|
3.06 L
Standard Deviation 0.856
|
3.04 L
Standard Deviation 0.754
|
SECONDARY outcome
Timeframe: Measured at clinic visits: 1, 4, 8 and 12 weeksPopulation: 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.
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=216 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Pre-bronchodilator FVC (L) - End-value
|
3.08 L
Standard Error 0.026 • Interval 0.026 to
|
3.05 L
Standard Error 0.026 • Interval 0.026 to
|
3.02 L
Standard Error 0.026 • Interval 0.026 to
|
3.02 L
Standard Error 0.025 • Interval 0.025 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic
Outcome measures
| Measure |
5 mg AZD9668
n=207 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=215 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Post-bronchodilator FVC (L) - Baseline
|
3.30 L
Standard Deviation 0.914
|
3.24 L
Standard Deviation 0.723
|
3.24 L
Standard Deviation 0.885
|
3.27 L
Standard Deviation 0.781
|
SECONDARY outcome
Timeframe: Measured at clinic visits: 1, 4, 8 and 12 weeksPopulation: 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.
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Outcome measures
| Measure |
5 mg AZD9668
n=207 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=215 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Post-bronchodilator FVC (L) - End-value
|
3.28 L
Standard Error 0.023 • Interval 0.023 to
|
3.26 L
Standard Error 0.024 • Interval 0.024 to
|
3.24 L
Standard Error 0.024 • Interval 0.024 to
|
3.22 L
Standard Error 0.023 • Interval 0.023 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
Inspiratory Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=200 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=216 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Pre-bronchodilator IC (L) - Baseline
|
2.22 L
Standard Deviation 0.680
|
2.14 L
Standard Deviation 0.563
|
2.15 L
Standard Deviation 0.662
|
2.17 L
Standard Deviation 0.574
|
SECONDARY outcome
Timeframe: Measured at clinic visits: 1, 4, 8 and 12 weeksPopulation: 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.
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=200 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=216 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Pre-bronchodilator IC (L) - End-value
|
2.15 L
Standard Error 0.027 • Interval 0.027 to
|
2.15 L
Standard Error 0.028 • Interval 0.028 to
|
2.16 L
Standard Error 0.027 • Interval 0.027 to
|
2.15 L
Standard Error 0.026 • Interval 0.026 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
Inspiratory Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic
Outcome measures
| Measure |
5 mg AZD9668
n=206 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=214 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Post-bronchodilator IC (L) - Baseline
|
2.37 L
Standard Deviation 0.709
|
2.30 L
Standard Deviation 0.601
|
2.28 L
Standard Deviation 0.677
|
2.32 L
Standard Deviation 0.628
|
SECONDARY outcome
Timeframe: Measured at clinic visits: 1, 4, 8 and 12 weeksPopulation: 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.
End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Outcome measures
| Measure |
5 mg AZD9668
n=206 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=199 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=201 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=214 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Post-bronchodilator IC (L) - End-value
|
2.29 L
Standard Error 0.025 • Interval 0.025 to
|
2.30 L
Standard Error 0.025 • Interval 0.025 to
|
2.31 L
Standard Error 0.025 • Interval 0.025 to
|
2.30 L
Standard Error 0.025 • Interval 0.025 to
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=217 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
PEF - Baseline Measured by Patient at Home (L/Min) in the Morning
|
222.33 L/min
Standard Deviation 83.177
|
219.86 L/min
Standard Deviation 90.395
|
216.99 L/min
Standard Deviation 91.299
|
221.79 L/min
Standard Deviation 89.005
|
SECONDARY outcome
Timeframe: Last 6 weeks on treatmentPopulation: 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.
Peak Expiratory Flow (L/min)
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=217 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
PEF - End-value Measured by Patient at Home (L/Min) in the Morning
|
214.30 L/min
Standard Error 2.899 • Interval 2.899 to
|
214.55 L/min
Standard Error 2.920 • Interval 2.92 to
|
212.35 L/min
Standard Error 2.944 • Interval 2.944 to
|
220.47 L/min
Standard Error 2.840 • Interval 2.84 to
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=217 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
FEV1 - Baseline Measured by Patient at Home (L) in the Morning
|
1.40 L
Standard Deviation 0.521
|
1.34 L
Standard Deviation 0.444
|
1.36 L
Standard Deviation 0.507
|
1.38 L
Standard Deviation 0.456
|
SECONDARY outcome
Timeframe: Last 6 weeks on treatmentPopulation: 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.
Forced Expiratory Volume in 1 second (L)
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=217 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
FEV1 - End-value Measured by Patient at Home (L) in the Morning
|
1.36 L
Standard Error 0.018 • Interval 0.018 to
|
1.35 L
Standard Error 0.018 • Interval 0.018 to
|
1.33 L
Standard Error 0.018 • Interval 0.018 to
|
1.34 L
Standard Error 0.018 • Interval 0.018 to
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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.
Outcome measures
| Measure |
5 mg AZD9668
n=207 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=200 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=214 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
EXACT - Baseline Total Score
|
43.17 Units on a scale
Standard Deviation 10.109
|
42.38 Units on a scale
Standard Deviation 8.166
|
42.37 Units on a scale
Standard Deviation 9.320
|
40.95 Units on a scale
Standard Deviation 9.725
|
SECONDARY outcome
Timeframe: Measured daily in the evening for 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
5 mg AZD9668
n=207 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=200 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=214 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
EXACT - End-value Total Score
|
39.97 Units on a scale
Standard Error 0.545 • Interval 0.545 to
|
39.72 Units on a scale
Standard Error 0.543 • Interval 0.543 to
|
40.59 Units on a scale
Standard Error 0.552 • Interval 0.552 to
|
39.71 Units on a scale
Standard Error 0.533 • Interval 0.533 to
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=217 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
BCSS - Baseline Total Score
|
4.85 Units on a scale
Standard Deviation 1.954
|
4.66 Units on a scale
Standard Deviation 1.526
|
4.79 Units on a scale
Standard Deviation 1.756
|
4.48 Units on a scale
Standard Deviation 1.782
|
SECONDARY outcome
Timeframe: Measured daily in the evening for 12 weeksPopulation: 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.
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
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=217 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
BCSS - End-value Total Score
|
4.09 Units on a scale
Standard Error 0.098 • Interval 0.098 to
|
4.03 Units on a scale
Standard Error 0.099 • Interval 0.099 to
|
4.25 Units on a scale
Standard Error 0.100 • Interval 0.1 to
|
4.20 Units on a scale
Standard Error 0.096 • Interval 0.096 to
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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).
Outcome measures
| Measure |
5 mg AZD9668
n=194 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=179 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=188 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=195 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Sputum Colour - Baseline
|
2.15 Units on a scale
Standard Deviation 1.069
|
2.34 Units on a scale
Standard Deviation 1.137
|
2.13 Units on a scale
Standard Deviation 0.956
|
2.16 Units on a scale
Standard Deviation 1.046
|
SECONDARY outcome
Timeframe: Measured at clinic visits:1, 4, 8 and 12 weeksPopulation: 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.
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
Outcome measures
| Measure |
5 mg AZD9668
n=194 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=179 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=188 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=195 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Sputum Colour - End Value
|
2.11 Units on a scale
Standard Error 0.062 • Interval 0.062 to
|
2.03 Units on a scale
Standard Error 0.065 • Interval 0.065 to
|
2.20 Units on a scale
Standard Error 0.063 • Interval 0.063 to
|
2.11 Units on a scale
Standard Error 0.062 • Interval 0.062 to
|
SECONDARY outcome
Timeframe: Last 6 weeks on treatmentPopulation: 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.
Daily average of number of inhalations of reliever medication
Outcome measures
| Measure |
5 mg AZD9668
n=209 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=204 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=215 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Use of Reliever Medication
|
4.28 Inhalations
Standard Error 0.173 • Interval 0.173 to
|
4.20 Inhalations
Standard Error 0.175 • Interval 0.175 to
|
4.65 Inhalations
Standard Error 0.175 • Interval 0.175 to
|
4.56 Inhalations
Standard Error 0.170 • Interval 0.17 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
Outcome measures
| Measure |
5 mg AZD9668
n=194 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=184 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=191 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=205 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Six-minute Walk Test - Distance Walked at Baseline (m)
|
386.2 m
Standard Deviation 125.22
|
402.2 m
Standard Deviation 111.98
|
384.9 m
Standard Deviation 115.50
|
386.0 m
Standard Deviation 132.48
|
SECONDARY outcome
Timeframe: Measured Day 1 and 12 weeksPopulation: 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.
distance walked on vist 6 - last on treatment clinic visit
Outcome measures
| Measure |
5 mg AZD9668
n=194 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=184 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=191 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=205 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Six-minute Walk Test - End-value Distance Walked (m)
|
396.7 m
Standard Error 4.74 • Interval 4.74 to
|
397.8 m
Standard Error 4.87 • Interval 4.87 to
|
411.2 m
Standard Error 4.76 • Interval 4.76 to
|
409.5 m
Standard Error 4.61 • Interval 4.61 to
|
SECONDARY outcome
Timeframe: Day 1Population: 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.
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)).
Outcome measures
| Measure |
5 mg AZD9668
n=199 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=187 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=194 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=210 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline
|
53.98 Scores on a scale
Standard Deviation 18.276
|
51.98 Scores on a scale
Standard Deviation 18.207
|
52.97 Scores on a scale
Standard Deviation 18.234
|
51.41 Scores on a scale
Standard Deviation 18.849
|
SECONDARY outcome
Timeframe: Measured Day 1 and 12 weeksPopulation: 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.
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)
Outcome measures
| Measure |
5 mg AZD9668
n=199 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=187 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=194 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=210 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
St George's Respiratory Questionnaire (COPD) - End-value Overall Score
|
49.50 Scores on a scale
Standard Error 1.014 • Interval 1.014 to
|
49.49 Scores on a scale
Standard Error 1.049 • Interval 1.049 to
|
47.93 Scores on a scale
Standard Error 1.023 • Interval 1.023 to
|
46.35 Scores on a scale
Standard Error 0.984 • Interval 0.984 to
|
SECONDARY outcome
Timeframe: Duration of the the treatment period - 12 weeksPopulation: 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.
Number of patients having a clinic defined disease exacerbation
Outcome measures
| Measure |
5 mg AZD9668
n=210 Participants
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=205 Participants
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 Participants
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=218 Participants
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Exacerbations - Clinic Defined
|
29 Participants
|
28 Participants
|
34 Participants
|
29 Participants
|
Adverse Events
5 mg AZD9668
20 mg AZD9668
60 mg AZD9668
Placebo
Serious adverse events
| Measure |
5 mg AZD9668
n=212 participants at risk
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=206 participants at risk
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 participants at risk
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=218 participants at risk
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
General disorders
GASTROINTESTINAL ULCER HAEMORRHAGE
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/212
|
0.97%
2/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Infections and infestations
ACUTE SINUSITIS
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Infections and infestations
LOBAR PNEUMONIA
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Infections and infestations
PNEUMONIA BACTERIAL
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Infections and infestations
SEPSIS
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Injury, poisoning and procedural complications
HUMERUS FRACTURE
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Investigations
BLOOD CREATININE INCREASED
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Investigations
BLOOD UREA INCREASED
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Investigations
ELECTROCARDIOGRAM T WAVE INVERSION
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Investigations
LIVER FUNCTION TEST ABNORMAL
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BILE DUCT CANCER
|
0.47%
1/212
|
0.00%
0/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Renal and urinary disorders
URETERIC OBSTRUCTION
|
0.00%
0/212
|
0.49%
1/206
|
0.00%
0/202
|
0.00%
0/218
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.47%
1/212
|
3.9%
8/206
|
3.5%
7/202
|
1.8%
4/218
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.47%
1/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
|
Respiratory, thoracic and mediastinal disorders
'RESPIRATORY FAILURE
|
0.00%
0/212
|
0.00%
0/206
|
0.50%
1/202
|
0.00%
0/218
|
|
Vascular disorders
THROMBOSIS
|
0.00%
0/212
|
0.00%
0/206
|
0.00%
0/202
|
0.46%
1/218
|
Other adverse events
| Measure |
5 mg AZD9668
n=212 participants at risk
AZD9668 2x2.5 mg oral tablets twice daily (bid) for 12 weeks
|
20 mg AZD9668
n=206 participants at risk
AZD9668 2x10 mg oral tablets twice daily (bid) for 12 weeks
|
60 mg AZD9668
n=202 participants at risk
AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks
|
Placebo
n=218 participants at risk
Matched Placebo Tablets
|
|---|---|---|---|---|
|
Infections and infestations
NASOPHARYNGITIS
|
7.1%
15/212
|
4.4%
9/206
|
4.5%
9/202
|
6.0%
13/218
|
|
Nervous system disorders
HEADACHE
|
1.4%
3/212
|
2.4%
5/206
|
2.5%
5/202
|
5.0%
11/218
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place