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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01023516
• Collaborator: (none)
• Enrollment: 615
• Locations: 67
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 9.2
• Patients Per Site Per Month: 1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: AZD9668; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 615 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60mg AZD9668 Administered Orally Twice Daily to Subjects With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Budesonide/Formoterol
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: AZD9668; 2 x 30 mg oral tablets bd for 12 weeks
Placebo Comparator: 2	Drug: Placebo; 2 x matched placebo to oral tablet bd for 12 weeks

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. Post-bronchodilator FEV1 (L) - End-value [up to week 12]

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

3. 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.

4. Pre-bronchodilator FVC (L) - End-value [up to week 12]

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

5. 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.

6. Post-bronchodilator FVC (L) - End-value [up to week 12]

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

7. 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.

8. End-value Pre-bronchodilator FEV6 (L) [up to week 12]

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

9. 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.

10. End-value Post-bronchodilator FEV6 (L) [up to week 12]

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

11. 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.

12. 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)

13. 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.

14. 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)

15. Pre-bronchodilator IC (L) - Baseline [Day 1]

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

16. Pre-bronchodilator IC (L) - End-value [up to week 12]

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

17. Post-bronchodilator IC (L) - Baseline [Day 1]

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

18. Post-bronchodilator IC (L) - End-value [up to week 12]

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

19. 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.

20. PEF - End-value Measured by Patient at Home (L/Min) in the Morning [Last 6 weeks on treatment]

    Peak expiratory flow (PEF)

21. 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.

22. FEV1 - End-value Measured by Patient at Home (L) in the Morning [Last 6 weeks on treatment]

    Forced Expiratory Volume in 1 second (L)

23. 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.

24. 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).

25. 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.

26. 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).

27. 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).

28. 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

29. Use of Reliever Medication [Last 6 weeks on treatment]

    Daily average of number of inhalations of reliever medication

30. Incremental Shuttle Walk Test - Baseline [Day 1]

    Endurance time (s)

31. Incremental Shuttle Walk Test - End Value [Week 12 - visit 6]

32. Endurance Shuttle Walk Test - Baseline [Day 1]

    Endurance time (s)

33. Endurance Shuttle Walk Test - End Value [Week 12 - visit 6]

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

34. 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)).

35. 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)

36. Exacerbations - Clinic Defined [Duration of the the treatment period - 12 weeks]

    Number of patients having a clinic defined disease exacerbation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Lovech		Bulgaria
2	Research Site	Pleven		Bulgaria
3	Research Site	Plovdiv		Bulgaria
4	Research Site	Russe		Bulgaria
5	Research Site	Sofia		Bulgaria
6	Research Site	Stara Zagora		Bulgaria
7	Research Site	Troyan		Bulgaria
8	Research Site	Varna		Bulgaria
9	Research Site	Jihlava		Czech Republic
10	Research Site	Jindrichuv Hradec		Czech Republic
11	Research Site	Kladno		Czech Republic
12	Research Site	Krnov		Czech Republic
13	Research Site	Novy Jicin		Czech Republic
14	Research Site	Pardubice		Czech Republic
15	Research Site	Praha 10		Czech Republic
16	Research Site	Praha 5		Czech Republic
17	Research Site	Rokycany		Czech Republic
18	Research Site	Trebic		Czech Republic
19	Research Site	Balassagyarmat		Hungary
20	Research Site	Budapest		Hungary
21	Research Site	Debrecen		Hungary
22	Research Site	Deszk		Hungary
23	Research Site	Gyor		Hungary
24	Research Site	Nyiregyhaza		Hungary
25	Research Site	Pecs		Hungary
26	Research Site	Szazhalombatta		Hungary
27	Research Site	Szombathely		Hungary
28	Research Site	Torokbalint		Hungary
29	Research Site	Vasarosnameny		Hungary
30	Research Site	Bialystok		Poland
31	Research Site	Gdynia		Poland
32	Research Site	Gorzow Wlkp		Poland
33	Research Site	Grodzisk Mazowiecki		Poland
34	Research Site	Jelenia Gora		Poland
35	Research Site	Katowice		Poland
36	Research Site	Kielce		Poland
37	Research Site	Krakow		Poland
38	Research Site	Lodz		Poland
39	Research Site	Lublin		Poland
40	Research Site	Pila		Poland
41	Research Site	Skierniewice		Poland
42	Research Site	Szczecin		Poland
43	Research Site	Tarnow		Poland
44	Research Site	Warszawa		Poland
45	Research Site	Wroclaw		Poland
46	Research Site	Deva	Hunedoara	Romania
47	Research Site	Bucharest		Romania
48	Research Site	Bucuresti		Romania
49	Research Site	Constanta		Romania
50	Research Site	Iasi		Romania
51	Research Site	Bardejov		Slovakia
52	Research Site	Bojnice		Slovakia
53	Research Site	Bratislava		Slovakia
54	Research Site	Dunajska Streda		Slovakia
55	Research Site	Humenne		Slovakia
56	Research Site	Kosice		Slovakia
57	Research Site	Liptovsky Hradok		Slovakia
58	Research Site	Nove Mesto Nad Vahom		Slovakia
59	Research Site	Nove Zamky		Slovakia
60	Research Site	Poprad		Slovakia
61	Research Site	Povazska Bystrica		Slovakia
62	Research Site	Presov		Slovakia
63	Research Site	Revuca		Slovakia
64	Research Site	Spisska Nova Ves		Slovakia
65	Research Site	Trnava		Slovakia
66	Research Site	Trstena		Slovakia
67	Research Site	Zilina		Slovakia

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Piotr Kuna, Professor, Samodzielny Publiczny ZOZ Uniwersytecki Szpital Kliniczny

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01023516
• Other Study ID Numbers: D0520C00020
• First Posted: Dec 2, 2009
• Last Update Posted: Aug 3, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by AstraZeneca: Chronic; obstructive; pulmonary; lung; respiratory disease; efficacy; placebo-controlled; COPD; FEV1; St Georges Respiratory Questionnaire
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

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 Detail	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.

Arm/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Period Title: Overall Study
STARTED	313	302
COMPLETED	289	284
NOT COMPLETED	24	18

Baseline Characteristics

Arm/Group Title	60 mg AZD9668	Placebo	Total
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets	Total of all reporting groups
Overall Participants	313	302	615
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	62	61	61.5
Sex: Female, Male (Count of Participants)
Female	80 25.6%	81 26.8%	161 26.2%
Male	233 74.4%	221 73.2%	454 73.8%

Outcome Measures

1. Primary Outcome

Title	Baseline Pre-bronchodilator FEV1 (L)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	309	301
Mean (Standard Deviation) [L]	1.49 (0.539)	1.44 (0.519)

2. Primary Outcome

Title	End-value Pre-bronchodilator FEV1 (L)
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	309	301
Least Squares Mean (Standard Error) [L]	1.45 (0.015)	1.43 (0.015)

3. Secondary Outcome

Title	Post-bronchodilator FEV1 (L) - Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	300
Mean (Standard Deviation) [L]	1.59 (0.530)	1.56 (0.518)

4. Secondary Outcome

Title	Post-bronchodilator FEV1 (L) - End-value
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	300
Least Squares Mean (Standard Error) [L]	1.56 (0.014)	1.54 (0.015)

5. Secondary Outcome

Title	Pre-bronchodilator FVC (L) - Baseline
Description	Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	309	301
Mean (Standard Deviation) [L]	2.98 (0.781)	2.94 (0.806)

6. Secondary Outcome

Title	Pre-bronchodilator FVC (L) - End-value
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	309	301
Least Squares Mean (Standard Error) [L]	2.94 (0.022)	2.93 (0.022)

7. Secondary Outcome

Title	Post-bronchodilator FVC (L) - Baseline
Description	Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	300
Mean (Standard Deviation) [L]	3.16 (0.787)	3.12 (0.822)

8. Secondary Outcome

Title	Post-bronchodilator FVC (L) - End-value
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	300
Least Squares Mean (Standard Error) [L]	3.11 (0.021)	3.11 (0.021)

9. Secondary Outcome

Title	Baseline Pre-bronchodilator FEV6 (L)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	309	301
Mean (Standard Deviation) [L]	2.68 (0.729)	2.61 (0.714)

10. Secondary Outcome

Title	End-value Pre-bronchodilator FEV6 (L)
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	309	301
Least Squares Mean (Standard Error) [L]	2.61 (0.019)	2.61 (0.019)

11. Secondary Outcome

Title	Baseline Post-bronchodilator FEV6 (L)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	300
Mean (Standard Deviation) [L]	2.85 (0.724)	2.79 (0.716)

12. Secondary Outcome

Title	End-value Post-bronchodilator FEV6 (L)
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	300
Least Squares Mean (Standard Error) [L]	2.77 (0.017)	2.78 (0.018)

13. Secondary Outcome

Title	Baseline Pre-bronchodilator FEF25-75% (L/Sec)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	307	301
Mean (Standard Deviation) [L/sec]	0.60 (0.380)	0.55 (0.324)

14. Secondary Outcome

Title	End-value Pre-bronchodilator FEF25-75% (L/Sec)
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	307	301
Least Squares Mean (Standard Error) [L/sec]	0.57 (0.016)	0.56 (0.016)

15. Secondary Outcome

Title	Baseline Post-bronchodilator FEF25-75% (L/Sec)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	299
Mean (Standard Deviation) [L/sec]	0.64 (0.367)	0.60 (0.333)

16. Secondary Outcome

Title	End-value Post-bronchodilator FEF25-75% (L/Sec)
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	299
Least Squares Mean (Standard Error) [L/sec]	0.62 (0.016)	0.61 (0.016)

17. Secondary Outcome

Title	Pre-bronchodilator IC (L) - Baseline
Description	Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	301
Mean (Standard Deviation) [L]	2.21 (0.661)	2.17 (0.661)

18. Secondary Outcome

Title	Pre-bronchodilator IC (L) - End-value
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	301
Least Squares Mean (Standard Error) [L]	2.13 (0.024)	2.14 (0.025)

19. Secondary Outcome

Title	Post-bronchodilator IC (L) - Baseline
Description	Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	299
Mean (Standard Deviation) [L]	2.33 (0.718)	2.30 (0.665)

20. Secondary Outcome

Title	Post-bronchodilator IC (L) - End-value
Description	End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF)
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	299
Least Squares Mean (Standard Error) [L]	2.30 (0.023)	2.27 (0.023)

21. Secondary Outcome

Title	PEF - Baseline Measured by Patient at Home (L/Min) in the Morning
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Mean (Standard Deviation) [L/min]	215.60 (98.406)	213.24 (96.803)

22. Secondary Outcome

Title	PEF - End-value Measured by Patient at Home (L/Min) in the Morning
Description	Peak expiratory flow (PEF)
Time Frame	Last 6 weeks on treatment

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Least Squares Mean (Standard Error) [L/min]	208.68 (2.153)	211.93 (2.189)

23. Secondary Outcome

Title	FEV1 - Baseline Measured by Patient at Home (L) in the Morning
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Mean (Standard Deviation) [L]	1.40 (0.546)	1.34 (0.516)

24. Secondary Outcome

Title	FEV1 - End-value Measured by Patient at Home (L) in the Morning
Description	Forced Expiratory Volume in 1 second (L)
Time Frame	Last 6 weeks on treatment

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Least Squares Mean (Standard Error) [L]	1.32 (0.012)	1.32 (0.012)

25. Secondary Outcome

Title	EXACT - Baseline Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	311	300
Mean (Standard Deviation) [units on a scale]	45.47 (9.683)	46.01 (8.900)

26. Secondary Outcome

Title	EXACT - End-value Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	311	300
Least Squares Mean (Standard Error) [units on a scale]	42.78 (0.473)	43.07 (0.480)

27. Secondary Outcome

Title	BCSS - Baseline Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Mean (Standard Deviation) [units on a scale]	5.26 (1.787)	5.44 (1.765)

28. Secondary Outcome

Title	BCSS - End-value Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Least Squares Mean (Standard Error) [units on a scale]	4.68 (0.085)	4.68 (0.086)

29. Secondary Outcome

Title	Sputum Colour - Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	300	298
Mean (Standard Deviation) [units on a scale]	1.87 (0.901)	1.88 (0.807)

30. Secondary Outcome

Title	Sputum Colour - End Value
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	300	298
Least Squares Mean (Standard Error) [units on a scale]	1.63 (0.042)	1.70 (0.042)

31. Secondary Outcome

Title	Use of Reliever Medication
Description	Daily average of number of inhalations of reliever medication
Time Frame	Last 6 weeks on treatment

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	310	299
Least Squares Mean (Standard Error) [inhalations]	3.40 (0.124)	3.37 (0.126)

32. Secondary Outcome

Title	Incremental Shuttle Walk Test - Baseline
Description	Endurance time (s)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Mean (Standard Deviation) [seconds]	351 (119.5)	352 (108.3)

33. Secondary Outcome

Title	Incremental Shuttle Walk Test - End Value
Time Frame	Week 12 - visit 6

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	297	287
Least Squares Mean (Standard Error) [seconds]	363.6 (3.39)	363.7 (3.44)

34. Secondary Outcome

Title	Endurance Shuttle Walk Test - Baseline
Description	Endurance time (s)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Mean (Standard Deviation) [seconds]	419 (269.4)	449 (292.9)

35. Secondary Outcome

Title	Endurance Shuttle Walk Test - End Value
Description	Assessed at vist 6 -( last on treatment clinic visit)
Time Frame	Week 12 - visit 6

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	299	286
Least Squares Mean (Standard Error) [seconds]	449.6 (10.49)	459.9 (10.68)

36. Secondary Outcome

Title	St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	295	280
Mean (Standard Deviation) [Scores on a scale]	54.52 (16.863)	54.87 (17.575)

37. Secondary Outcome

Title	St George's Respiratory Questionnaire (COPD) - End-value Overall Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	295	280
Least Squares Mean (Standard Error) [Scores on a scale]	49.89 (0.777)	50.66 (0.796)

38. Secondary Outcome

Title	Exacerbations - Clinic Defined
Description	Number of patients having a clinic defined disease exacerbation.
Time Frame	Duration of the the treatment period - 12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	60 mg AZD9668	Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks	Matched Placebo Tablets
Measure Participants	312	301
Number [Participants]	22 7%	29 9.6%

Adverse Events

Arm/Group Title	60 mg AZD9668		Placebo
Arm/Group Description	AZD9668 2x30 mg oral tablets twice daily (bid) for 12 weeks		Matched Placebo Tablets
All Cause Mortality
	60 mg AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	60 mg AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/313 (2.9%)		14/302 (4.6%)
Cardiac disorders
MYOCARDIAL ISCHAEMIA	0/313 (0%)		2/302 (0.7%)
ACUTE MYOCARDIAL INFARCTION	0/313 (0%)		1/302 (0.3%)
ANGINA PECTORIS	0/313 (0%)		1/302 (0.3%)
BUNDLE BRANCH BLOCK RIGHT	1/313 (0.3%)		0/302 (0%)
CARDIAC FAILURE	0/313 (0%)		1/302 (0.3%)
Infections and infestations
PNEUMONIA	1/313 (0.3%)		3/302 (1%)
POST PROCEDURAL INFECTION	0/313 (0%)		1/302 (0.3%)
PYELONEPHRITIS ACUTE	1/313 (0.3%)		0/302 (0%)
Injury, poisoning and procedural complications
RADIUS FRACTURE	1/313 (0.3%)		0/302 (0%)
TIBIA FRACTURE	0/313 (0%)		1/302 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LARYNGEAL CANCER	0/313 (0%)		1/302 (0.3%)
LUNG NEOPLASM MALIGNANT	1/313 (0.3%)		0/302 (0%)
LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED	0/313 (0%)		1/302 (0.3%)
Nervous system disorders
SYNCOPE	0/313 (0%)		0/302 (0%)
Renal and urinary disorders
RENAL COLIC	0/313 (0%)		1/302 (0.3%)
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	4/313 (1.3%)		1/302 (0.3%)
ACUTE PULMONARY OEDEMA	0/313 (0%)		1/302 (0.3%)
Other (Not Including Serious) Adverse Events
	60 mg AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/313 (0%)		0/302 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.