Trial Outcomes & Findings for Efficacy and Safety of Twice Daily 60mg AZD9668 in COPD for 12 Weeks in Patients on Background Budesonide/Formoterol (NCT NCT01023516)

NCT ID: NCT01023516

Last Updated: 2012-08-03

Results Overview

Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 615 participants
• Primary outcome timeframe: Day 1
• Results posted on: 2012-08-03

Participant Flow

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).

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.

Participant milestones

Measure	60 mg AZD9668 AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo Matched Placebo Tablets
Overall Study STARTED	313	302
Overall Study COMPLETED	289	284
Overall Study NOT COMPLETED	24	18

Reasons for withdrawal

Measure	60 mg AZD9668 AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo Matched Placebo Tablets
Overall Study Voluntary discontinuation	7	5
Overall Study Adverse Event	9	6
Overall Study Safety reason	0	3
Overall Study Study-specific criteria	4	2
Overall Study Incorrect enrolment	4	2

Baseline Characteristics

Efficacy and Safety of Twice Daily 60mg AZD9668 in COPD for 12 Weeks in Patients on Background Budesonide/Formoterol

Baseline characteristics by cohort

Measure	60 mg AZD9668 n=313 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=302 Participants Matched Placebo Tablets	Total n=615 Participants Total of all reporting groups
Age Continuous	62 Years n=5 Participants	61 Years n=7 Participants	61.5 Years n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	81 Participants n=7 Participants	161 Participants n=5 Participants
Sex: Female, Male Male	233 Participants n=5 Participants	221 Participants n=7 Participants	454 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=309 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Baseline Pre-bronchodilator FEV1 (L)	1.49 L Standard Deviation 0.539	1.44 L Standard Deviation 0.519

PRIMARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=309 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
End-value Pre-bronchodilator FEV1 (L)	1.45 L Standard Error 0.015 • Interval 0.015 to	1.43 L Standard Error 0.015 • Interval 0.015 to

SECONDARY outcome

Timeframe: 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.

Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
Post-bronchodilator FEV1 (L) - Baseline	1.59 L Standard Deviation 0.530	1.56 L Standard Deviation 0.518

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
Post-bronchodilator FEV1 (L) - End-value	1.56 L Standard Error 0.014 • Interval 0.014 to	1.54 L Standard Error 0.015 • Interval 0.015 to

SECONDARY outcome

Timeframe: 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.

Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=309 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Pre-bronchodilator FVC (L) - Baseline	2.98 L Standard Deviation 0.781	2.94 L Standard Deviation 0.806

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=309 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Pre-bronchodilator FVC (L) - End-value	2.94 L Standard Error 0.022 • Interval 0.022 to	2.93 L Standard Error 0.022 • Interval 0.022 to

SECONDARY outcome

Timeframe: 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.

Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
Post-bronchodilator FVC (L) - Baseline	3.16 L Standard Deviation 0.787	3.12 L Standard Deviation 0.822

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
Post-bronchodilator FVC (L) - End-value	3.11 L Standard Error 0.021 • Interval 0.021 to	3.11 L Standard Error 0.021 • Interval 0.021 to

SECONDARY outcome

Timeframe: 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.

Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=309 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Baseline Pre-bronchodilator FEV6 (L)	2.68 L Standard Deviation 0.729	2.61 L Standard Deviation 0.714

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=309 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
End-value Pre-bronchodilator FEV6 (L)	2.61 L Standard Error 0.019 • Interval 0.019 to	2.61 L Standard Error 0.019 • Interval 0.019 to

SECONDARY outcome

Timeframe: 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.

Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post after bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
Baseline Post-bronchodilator FEV6 (L)	2.85 L Standard Deviation 0.724	2.79 L Standard Deviation 0.716

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
End-value Post-bronchodilator FEV6 (L)	2.77 L Standard Error 0.017 • Interval 0.017 to	2.78 L Standard Error 0.018 • Interval 0.018 to

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	60 mg AZD9668 n=307 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Baseline Pre-bronchodilator FEF25-75% (L/Sec)	0.60 L/sec Standard Deviation 0.380	0.55 L/sec Standard Deviation 0.324

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=307 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
End-value Pre-bronchodilator FEF25-75% (L/Sec)	0.57 L/sec Standard Error 0.016 • Interval 0.016 to	0.56 L/sec Standard Error 0.016 • Interval 0.016 to

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=299 Participants Matched Placebo Tablets
Baseline Post-bronchodilator FEF25-75% (L/Sec)	0.64 L/sec Standard Deviation 0.367	0.60 L/sec Standard Deviation 0.333

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=299 Participants Matched Placebo Tablets
End-value Post-bronchodilator FEF25-75% (L/Sec)	0.62 L/sec Standard Error 0.016 • Interval 0.016 to	0.61 L/sec Standard Error 0.016 • Interval 0.016 to

SECONDARY outcome

Timeframe: 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.

Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Pre-bronchodilator IC (L) - Baseline	2.21 L Standard Deviation 0.661	2.17 L Standard Deviation 0.661

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Pre-bronchodilator IC (L) - End-value	2.13 L Standard Error 0.024 • Interval 0.024 to	2.14 L Standard Error 0.025 • Interval 0.025 to

SECONDARY outcome

Timeframe: 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.

Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=299 Participants Matched Placebo Tablets
Post-bronchodilator IC (L) - Baseline	2.33 L Standard Deviation 0.718	2.30 L Standard Deviation 0.665

SECONDARY outcome

Timeframe: 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.

End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=299 Participants Matched Placebo Tablets
Post-bronchodilator IC (L) - End-value	2.30 L Standard Error 0.023 • Interval 0.023 to	2.27 L Standard Error 0.023 • Interval 0.023 to

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
PEF - Baseline Measured by Patient at Home (L/Min) in the Morning	215.60 L/min Standard Deviation 98.406	213.24 L/min Standard Deviation 96.803

SECONDARY outcome

Timeframe: 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.

Peak expiratory flow (PEF)

Outcome measures

Measure	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
PEF - End-value Measured by Patient at Home (L/Min) in the Morning	208.68 L/min Standard Error 2.153 • Interval 2.153 to	211.93 L/min Standard Error 2.189 • Interval 2.189 to

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
FEV1 - Baseline Measured by Patient at Home (L) in the Morning	1.40 L Standard Deviation 0.546	1.34 L Standard Deviation 0.516

SECONDARY outcome

Timeframe: 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.

Forced Expiratory Volume in 1 second (L)

Outcome measures

Measure	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
FEV1 - End-value Measured by Patient at Home (L) in the Morning	1.32 L Standard Error 0.012 • Interval 0.012 to	1.32 L Standard Error 0.012 • Interval 0.012 to

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=311 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
EXACT - Baseline Total Score	45.47 units on a scale Standard Deviation 9.683	46.01 units on a scale Standard Deviation 8.900

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	60 mg AZD9668 n=311 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=300 Participants Matched Placebo Tablets
EXACT - End-value Total Score	42.78 units on a scale Standard Error 0.473 • Interval 0.473 to	43.07 units on a scale Standard Error 0.480 • Interval 0.48 to

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
BCSS - Baseline Total Score	5.26 units on a scale Standard Deviation 1.787	5.44 units on a scale Standard Deviation 1.765

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
BCSS - End-value Total Score	4.68 units on a scale Standard Error 0.085 • Interval 0.085 to	4.68 units on a scale Standard Error 0.086 • Interval 0.086 to

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=300 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=298 Participants Matched Placebo Tablets
Sputum Colour - Baseline	1.87 units on a scale Standard Deviation 0.901	1.88 units on a scale Standard Deviation 0.807

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=300 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=298 Participants Matched Placebo Tablets
Sputum Colour - End Value	1.63 units on a scale Standard Error 0.042 • Interval 0.042 to	1.70 units on a scale Standard Error 0.042 • Interval 0.042 to

SECONDARY outcome

Timeframe: 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.

Daily average of number of inhalations of reliever medication

Outcome measures

Measure	60 mg AZD9668 n=310 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=299 Participants Matched Placebo Tablets
Use of Reliever Medication	3.40 inhalations Standard Error 0.124 • Interval 0.124 to	3.37 inhalations Standard Error 0.126 • Interval 0.126 to

SECONDARY outcome

Timeframe: 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.

Endurance time (s)

Outcome measures

Measure	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Incremental Shuttle Walk Test - Baseline	351 seconds Standard Deviation 119.5	352 seconds Standard Deviation 108.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	60 mg AZD9668 n=297 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=287 Participants Matched Placebo Tablets
Incremental Shuttle Walk Test - End Value	363.6 seconds Standard Error 3.39 • Interval 3.39 to	363.7 seconds Standard Error 3.44 • Interval 3.44 to

SECONDARY outcome

Timeframe: 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.

Endurance time (s)

Outcome measures

Measure	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Endurance Shuttle Walk Test - Baseline	419 seconds Standard Deviation 269.4	449 seconds Standard Deviation 292.9

SECONDARY outcome

Timeframe: 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.

Assessed at vist 6 -( last on treatment clinic visit)

Outcome measures

Measure	60 mg AZD9668 n=299 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=286 Participants Matched Placebo Tablets
Endurance Shuttle Walk Test - End Value	449.6 seconds Standard Error 10.49 • Interval 10.49 to	459.9 seconds Standard Error 10.68 • Interval 10.68 to

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=295 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=280 Participants Matched Placebo Tablets
St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline	54.52 Scores on a scale Standard Deviation 16.863	54.87 Scores on a scale Standard Deviation 17.575

SECONDARY outcome

Timeframe: 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.

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	60 mg AZD9668 n=295 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=280 Participants Matched Placebo Tablets
St George's Respiratory Questionnaire (COPD) - End-value Overall Score	49.89 Scores on a scale Standard Error 0.777 • Interval 0.777 to	50.66 Scores on a scale Standard Error 0.796 • Interval 0.796 to

SECONDARY outcome

Timeframe: 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.

Number of patients having a clinic defined disease exacerbation.

Outcome measures

Measure	60 mg AZD9668 n=312 Participants AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=301 Participants Matched Placebo Tablets
Exacerbations - Clinic Defined	22 Participants	29 Participants

Adverse Events

60 mg AZD9668

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	60 mg AZD9668 n=313 participants at risk AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Placebo n=302 participants at risk Matched Placebo Tablets
Cardiac disorders MYOCARDIAL ISCHAEMIA	0.00% 0/313	0.66% 2/302
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.00% 0/313	0.33% 1/302
Cardiac disorders ANGINA PECTORIS	0.00% 0/313	0.33% 1/302
Cardiac disorders BUNDLE BRANCH BLOCK RIGHT	0.32% 1/313	0.00% 0/302
Cardiac disorders CARDIAC FAILURE	0.00% 0/313	0.33% 1/302
Infections and infestations PNEUMONIA	0.32% 1/313	0.99% 3/302
Infections and infestations POST PROCEDURAL INFECTION	0.00% 0/313	0.33% 1/302
Infections and infestations PYELONEPHRITIS ACUTE	0.32% 1/313	0.00% 0/302
Injury, poisoning and procedural complications RADIUS FRACTURE	0.32% 1/313	0.00% 0/302
Injury, poisoning and procedural complications TIBIA FRACTURE	0.00% 0/313	0.33% 1/302
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LARYNGEAL CANCER	0.00% 0/313	0.33% 1/302
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	0.32% 1/313	0.00% 0/302
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED	0.00% 0/313	0.33% 1/302
Nervous system disorders SYNCOPE	0.00% 0/313	0.00% 0/302
Renal and urinary disorders RENAL COLIC	0.00% 0/313	0.33% 1/302
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1.3% 4/313	0.33% 1/302
Respiratory, thoracic and mediastinal disorders ACUTE PULMONARY OEDEMA	0.00% 0/313	0.33% 1/302

Other adverse events

Adverse event data not reported

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place