Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01054170
• Collaborator: (none)
• Enrollment: 52
• Locations: 9
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate structural changes effected by AD9668 in the airways of adults with Chronic Obstructive Pulmonary Disease (COPD) by Multi-Slice Computed Tomography (MSCT)

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-week, Phase II, Double-blind, Placebo-Controlled, Randomised, Parallel-Group, Multi-Centre Study to Assess the Effect of 60mg AZD9668 Administered Orally Twice Daily on Structural Changes in the Airways by Multi-Slice Computed Tomography in Patients With Chronic Obstructive Pulmonary Disease.
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD9668	Drug: AZD9668; 2 x 30 mg oral tablets twice daily (bid) for 12 weeks
Placebo Comparator: Placebo	Drug: Placebo; 2 x matched placebo to oral tablet twice daily (bid) for 12 weeks

Outcome Measures

Primary Outcome Measures

1. AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm) [Measured after 12 weeks treatment (day 84)]

   AWT-Pi10 (mm) as a measure of structural changes in airways. End of treatment Least Squares Mean.

Secondary Outcome Measures

1. 5th Generation Wall Area Percentage [Measured after 12 weeks treatment (day 84)]

   5th Generation Wall Area Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.

2. Air Trapping Index (ATI) on Expiratory Scans [Measured after 12 weeks treatment (day 84)]

   ATI Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.

3. Pre-bronchodilator Inspiratory Capacity (IC) [Measured after 12 weeks treatment (day 84)]

   Inspiratory Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.

4. Pre-bronchodilator Total Lung Capacity (TLC) [Measured after 12 weeks treatment (day 84)]

   Total Lung Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.

5. Pre-bronchodilator Functional Residual Capacity (FRC) [Measured after 12 weeks treatment (day 84)]

   Functional Residual Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.

6. Pre-bronchodilator Residual Volume (RV) [Measured after 12 weeks treatment (day 84)]

   Residual volume (L) as a measure of lung function. End of treatment Least Squares Mean.

7. Pre-bronchodilator Specific Airway Conductance (SGaw) [Measured after 12 weeks treatment (day 84)]

   Specific Airway Conductance as a measure of lung function. End of treatment Least Squares Mean.

8. Pre-bronchodilator Diffusion Capacity of Carbon Monoxide (DLco) [Measured after 12 weeks treatment (day 84)]

   Capacity of Carbon Monoxide as a measure of lung function. End of treatment Least Squares Mean.

9. Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [Measured after 12 weeks treatment (day 84)]

   Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

10. Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [Measured after 12 weeks treatment (day 84)]

    Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

11. Pre-bronchodilator Forced Vital Capacity (FVC) [Measured after 12 weeks treatment (day 84)]

    Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

12. Post-bronchodilator Forced Vital Capacity (FVC) [Measured after 12 weeks treatment (day 84)]

    Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

13. Pre-bronchodilator Slow Vital Capacity (SVC) [Measured after 12 weeks treatment (day 84)]

    Slow Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

14. Post-bronchodilator Slow Vital Capacity (SVC) [Measured after 12 weeks treatment (day 84)]

    Slow Vital capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).

15. Peak Expiratory Flow (PEF) Morning (Daily Recordings) [Average from measurements recorded daily by patient in last 6 weeks of treatment.]

    Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning.

16. Peak Expiratory Flow (PEF) Evening (Daily Recordings) [Average from measurements recorded daily by patient in last 6 weeks of treatment.]

    Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each evening .

17. Forced Expiratory Volume in 1 Second (FEV1) Morning (Daily Recordings) [Average from measurements recorded daily by patient in last 6 weeks of treatment.]

    Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning.

18. Forced Expiratory Volume in 1 Second (FEV1) Evening (Daily Recordings) [Average from measurements recorded daily by patient in last 6 weeks of treatment.]

    Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each evening.

19. Breathlessness, Cough and Sputum Scale (BCSS) Total Score [Average from measurements recorded daily by patient in last 6 weeks of 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).

20. EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score [Average from measurements recorded daily by patient in last 6 weeks of 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).

21. St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Overall Score [Measured after 12 weeks treatment (day 84)]

    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)).

22. Percentage of Reliever Free Days in Last Six Weeks of Treatment [Average from measurements recorded daily by patient in last 6 weeks of treatment.]

    Percentage of reliever free days in last 6 weeks on treatment.

23. Exacerbations [Exacerbations were recorded at all study visits (after 1, 4, 8, and 12 weeks of treatment and at follow up)]

    Number of patients experiencing disease exacerbations on treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 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 >= 40 and < =70 % of predicted post-bronchodilator

• Ex-smokers for at least 12 months

Exclusion Criteria:

• Past history or current evidence of clinically significant heart disease

• Current diagnosis of asthma

• Worsening of COPD requiring hospitalisation and/or treatment with antibiotics and/or 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	Kingston	Ontario	Canada
2	Research Site	Quebec		Canada
3	Research Site	Hellerup		Denmark
4	Research Site	Hvidovre		Denmark
5	Research Site	Odensec		Denmark
6	Research Site	Breda		Netherlands
7	Research Site	Nieuwegein		Netherlands
8	Research Site	Bucuresti		Romania
9	Research Site	Kyiv		Ukraine

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Professor Asger Dirksen, Gentofte Hospital, Department of Lung Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01054170
• Other Study ID Numbers: D0520C00014
• First Posted: Jan 22, 2010
• Last Update Posted: Aug 20, 2012
• Last Verified: Aug 1, 2012

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

Study Results

Participant Flow

Recruitment Details	First patient enrolled: 06 January 2010; Last patient completed: 17 November 2010; Twelve centres across 5 countries participated in this study: Canada (2), Denmark (3), The Netherlands (2), Romania (2) and Ukraine (3).
Pre-assignment Detail	Tiotropium maintenance therapy and reliever medication were commenced at screening, except for patients on inhaled corticosteroids (ICS, ICS/LABA) who were required to stop these at enrolment and commence on tiotropium and reliever medication at the same time. These patients received tiotropium for a period of at least 3 weeks before screening.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Period Title: Overall Study
STARTED	25	27
COMPLETED	21	21
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	AZD9668	Placebo	Total
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid	Total of all reporting groups
Overall Participants	25	27	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.2 (65)	7.7 (66)	7.45 (131)
Sex: Female, Male (Count of Participants)
Female	6 24%	10 37%	16 30.8%
Male	19 76%	17 63%	36 69.2%

Outcome Measures

1. Primary Outcome

Title	AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm)
Description	AWT-Pi10 (mm) as a measure of structural changes in airways. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	17	19
Least Squares Mean (Standard Error) [mm]	3.84 (0.021)	3.83 (0.017)

2. Secondary Outcome

Title	5th Generation Wall Area Percentage
Description	5th Generation Wall Area Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	17	19
Least Squares Mean (Standard Error) [Percentage Area]	66.21 (0.275)	65.94 (0.234)

3. Secondary Outcome

Title	Air Trapping Index (ATI) on Expiratory Scans
Description	ATI Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	15	13
Least Squares Mean (Standard Error) [ATI Percentage]	54.56 (1.706)	57.12 (1.599)

4. Secondary Outcome

Title	Pre-bronchodilator Inspiratory Capacity (IC)
Description	Inspiratory Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	24	23
Least Squares Mean (Standard Error) [L]	2.56 (0.154)	2.39 (0.153)

5. Secondary Outcome

Title	Pre-bronchodilator Total Lung Capacity (TLC)
Description	Total Lung Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	24	23
Least Squares Mean (Standard Error) [L]	7.03 (0.178)	6.92 (0.177)

6. Secondary Outcome

Title	Pre-bronchodilator Functional Residual Capacity (FRC)
Description	Functional Residual Capacity (L) as a measure of lung function. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	23	23
Least Squares Mean (Standard Error) [L]	4.41 (0.165)	4.21 (0.158)

7. Secondary Outcome

Title	Pre-bronchodilator Residual Volume (RV)
Description	Residual volume (L) as a measure of lung function. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	24	23
Least Squares Mean (Standard Error) [L]	3.64 (0.161)	3.73 (0.161)

8. Secondary Outcome

Title	Pre-bronchodilator Specific Airway Conductance (SGaw)
Description	Specific Airway Conductance as a measure of lung function. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	24	23
Least Squares Mean (Standard Error) [1/[s*kPa]]	0.52 (0.034)	0.48 (0.034)

9. Secondary Outcome

Title	Pre-bronchodilator Diffusion Capacity of Carbon Monoxide (DLco)
Description	Capacity of Carbon Monoxide as a measure of lung function. End of treatment Least Squares Mean.
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	23	23
Least Squares Mean (Standard Error) [mmol/kPa*min]	5.49 (0.204)	5.67 (0.209)

10. Secondary Outcome

Title	Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Description	Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L]	1.51 (0.048)	1.49 (0.050)

11. Secondary Outcome

Title	Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Description	Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	21	23
Least Squares Mean (Standard Error) [L]	1.60 (0.050)	1.58 (0.050)

12. Secondary Outcome

Title	Pre-bronchodilator Forced Vital Capacity (FVC)
Description	Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L]	3.25 (0.084)	3.14 (0.083)

13. Secondary Outcome

Title	Post-bronchodilator Forced Vital Capacity (FVC)
Description	Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	21	23
Least Squares Mean (Standard Error) [L]	3.34 (0.083)	3.34 (0.080)

14. Secondary Outcome

Title	Pre-bronchodilator Slow Vital Capacity (SVC)
Description	Slow Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L]	3.42 (0.069)	3.38 (0.068)

15. Secondary Outcome

Title	Post-bronchodilator Slow Vital Capacity (SVC)
Description	Slow Vital capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	21	23
Least Squares Mean (Standard Error) [L]	3.56 (0.063)	3.44 (0.061)

16. Secondary Outcome

Title	Peak Expiratory Flow (PEF) Morning (Daily Recordings)
Description	Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning.
Time Frame	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L/min]	255.82 (9.956)	244.16 (9.871)

17. Secondary Outcome

Title	Peak Expiratory Flow (PEF) Evening (Daily Recordings)
Description	Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each evening .
Time Frame	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L/min]	264.15 (10.02)	254.31 (9.966)

18. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) Morning (Daily Recordings)
Description	Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning.
Time Frame	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L]	1.49 (0.065)	1.29 (0.066)

19. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) Evening (Daily Recordings)
Description	Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each evening.
Time Frame	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [L]	1.51 (0.062)	1.30 (0.064)

20. Secondary Outcome

Title	Breathlessness, Cough and Sputum Scale (BCSS) 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	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [Total Score]	2.33 (0.319)	3.36 (0.301)

21. Secondary Outcome

Title	EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) 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	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	26
Least Squares Mean (Standard Error) [Total Score]	28.48 (2.065)	33.26 (2.013)

22. Secondary Outcome

Title	St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) 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)).
Time Frame	Measured after 12 weeks treatment (day 84)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	23
Least Squares Mean (Standard Error) [Scores on a scale]	35.64 (2.364)	39.61 (2.389)

23. Secondary Outcome

Title	Percentage of Reliever Free Days in Last Six Weeks of Treatment
Description	Percentage of reliever free days in last 6 weeks on treatment.
Time Frame	Average from measurements recorded daily by patient in last 6 weeks of 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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Least Squares Mean (Standard Error) [percentage of days]	34.23 (6.394)	26.43 (6.001)

24. Secondary Outcome

Title	Exacerbations
Description	Number of patients experiencing disease exacerbations on treatment.
Time Frame	Exacerbations were recorded at all study visits (after 1, 4, 8, and 12 weeks of treatment and at follow up)

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	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg bid	Placebo 2 tablets bid
Measure Participants	25	27
Number [Participants]	0 0%	5 18.5%

Adverse Events

Arm/Group Title	AZD9668		Placebo
Arm/Group Description	AZD9668 2x30mg bid		Placebo 2 tablets bid
All Cause Mortality
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		1/27 (3.7%)
Injury, poisoning and procedural complications
POST PROCEDURAL COMPLICATION	0/25 (0%)		1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/25 (32%)		8/27 (29.6%)
Gastrointestinal disorders
DRY MOUTH	0/25 (0%)		2/27 (7.4%)
General disorders
ASTHENIA	0/25 (0%)		2/27 (7.4%)
Infections and infestations
NASOPHARYNGITIS	5/25 (20%)		2/27 (7.4%)
Nervous system disorders
DIZZINESS	2/25 (8%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/25 (0%)		3/27 (11.1%)
BRONCHIAL WALL THICKENING	1/25 (4%)		2/27 (7.4%)
DYSPNOEA	0/25 (0%)		2/27 (7.4%)

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.