CODEX: Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00489853
• Collaborator: (none)
• Enrollment: 137
• Locations: 9
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 15.2
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect on exercise tolerance, lung function and symptoms after treatment with Symbicort, Oxis or placebo in patients with severe chronic obstructive pulmonary disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: budesonide/formoterol Turbuhaler 320/9µg; Drug: formoterol Turbuhaler 9µg; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-centre, Randomised, Double-blind, Cross-over Design Study to Evaluate Efficacy on Exercise Tolerance of Symbicort ®(Budesonide/Formoterol) 320/9μg One Inhalation Twice Daily Compared With Placebo and Oxis® 9μg One Inhalation Twice Daily in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD).
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Symbicort then Formoterol then Placebo Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily, then Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Placebo, 1 inhalation twice daily	Drug: budesonide/formoterol Turbuhaler 320/9µg; Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms; Drug: formoterol Turbuhaler 9µg; Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily; Other: Placebo; Placebo, 1 inhalation twice daily
Experimental: Formoterol then Symbicort then Placebo Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily, then Placebo, 1 inhalation twice daily	Drug: budesonide/formoterol Turbuhaler 320/9µg; Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms; Drug: formoterol Turbuhaler 9µg; Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily; Other: Placebo; Placebo, 1 inhalation twice daily
Placebo Comparator: Placebo then Formoterol then Symbicort Placebo, 1 inhalation twice daily, then Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Drug: budesonide/formoterol Turbuhaler 320/9µg; Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms; Drug: formoterol Turbuhaler 9µg; Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily; Other: Placebo; Placebo, 1 inhalation twice daily

Outcome Measures

Primary Outcome Measures

1. Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 1 Hour Post-dose [Single measurement taken1 hour post-dose at the end of each 1-week treatment period]

   Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods.

Secondary Outcome Measures

1. Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 6 Hour Post-dose [Single measurement taken 6 hours post-dose at the end of each 1-week treatment period]

   Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods.

2. Forced Expiratory Flow (FEV1) Pre-dose [Pre-dose at the start of treatment and pre-dose after one week of treatment]

   The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment.

3. Forced Vital Capacity (FVC) Pre-dose [Pre-dose at the start of treatment and pre-dose after one week of treatment]

   The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment.

4. Vital Capacity (VC) Pre-dose (Change From Pre-treatment to Treatment) [Pre-dose at the start of treatment and pre-dose after one week of treatment]

   The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment.

5. Peak Expiratory Flow (PEF) Before Morning Dose [Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period]

   The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period.

6. Sleep Score [Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period]

   The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (symptoms did not cause a sleep problem) to 4 (did not sleep at all due to symptoms).

7. Breathlessness Score [Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period]

   The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any difficulty in breathing) to 4 (almost constant difficulties in breathing). All patients with data from both periods are included.

8. Chest Tightness Score [Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period]

   The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any discomfort) to 4 (almost constant discomfort).

9. Cough Score [Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period]

   The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of coughing) to 4 (never free of need to cough).

10. Number of Inhalations of Reliever Medication [Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period]

    The change in average daily use for the run-in or wash-out period to the average daily use of the subsequent treatment period.

11. Borg CR10 Score Before Exercise Endurance Time (EET) Performed 1 Hour Post-dose [Single measurement performed at rest prior to exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    The Borg CR10 Scale consists of 10-point score that the patients pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness. Patients are allowed to assign an even higher number depending on their perceived level of breathlessness).

12. Borg CR10 Score After Exercise Endurance Time (EET) Performed 1 Hour Post-dose [Single measurement performed after exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort).

13. Borg CR10 Score Before Exercise Endurance Time (EET) Performed 6 Hour Post-dose [Single measurement performed at rest prior to exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort).

14. Borg CR10 Score After Exercise Endurance Time (EET) Performed 6 Hours Post-dose [Single measurement performed after exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). All patients with data are included.

15. Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 1 Hour Postdose [Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

16. Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose [Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

17. Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

18. Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 1hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

19. Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

20. Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

21. Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

22. Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

23. Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

24. Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

25. Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

26. Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 6 hous post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

27. Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET) [Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

28. Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET [Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period]

    Treatment means from individual participant data.

29. SGRQ-C (St. George's Respiratory Questionnaire for COPD Patients) Total Score [Single measurement taken at the end of each 1-week treatment period]

    Score from a questionnaire, with scores ranging form 0 (perfect health) to 100 (worst possible state). Includes all patients with data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• =40 years of age

• diagnosed COPD with symptoms >= 2 years

• pre-bronchodilatory FEV1 <=50% of PN

Exclusion Criteria:

• Current respiratory tract disorder other than COPD

• history of asthma or rhinitis

• significant or unstable cardiovascular disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Berlin		Germany
2	Research Site	Erfurt		Germany
3	Research Site	Fulda		Germany
4	Research Site	Furth		Germany
5	Research Site	Geesthacht		Germany
6	Research Site	Grobhansdorf		Germany
7	Research Site	Leipzig		Germany
8	Research Site	Neuruppin		Germany
9	Research Site	Basel	Basel Stadt	Switzerland

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Tomas Andersson, MD, AstraZeneca
• Principal Investigator: Heinrich Worth, MD, Akademisches Lehrkrankenhaus der Universität Erlangen-Nürnberg, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00489853
• Other Study ID Numbers: D5892C00014; Eudract No: 2006-006519-60
• First Posted: Jun 21, 2007
• Last Update Posted: Aug 30, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by AstraZeneca: COPD
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Budesonide; Formoterol Fumarate

Study Results

Participant Flow

Recruitment Details	Patients were recruited in 12 centers in Germany and 12 centers in Switzerland.
Pre-assignment Detail	Among 137 enrolled patients, 26 patients were not randomised (14 due to violation of inclusion/exclusion criteria, 2 due to adverse events, 1 due to development of study-specific discontinuation criteria, 7 due to voluntary discontinuation, 1 due to lost to follow-up, and 1 due to other reason.)

Arm/Group Title	Symbicort Then Formoterol Then Placebo	Formoterol Then Symbicort Then Placebo	Placebo Then Formoterol Then Symbicort
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily, then Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Placebo, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily, then Placebo, 1 inhalation twice daily	Placebo, 1 inhalation twice daily, then Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily, then Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily
Period Title: Treatment Period 1
STARTED	36	37	38
COMPLETED	36	37	38
NOT COMPLETED	0	0	0
Period Title: Treatment Period 1
STARTED	36	37	38
COMPLETED	35	34	32
NOT COMPLETED	1	3	6
Period Title: Treatment Period 1
STARTED	33	35	33
COMPLETED	33	35	33
NOT COMPLETED	0	0	0
Period Title: Treatment Period 1
STARTED	33	35	33
COMPLETED	29	32	31
NOT COMPLETED	4	3	2
Period Title: Treatment Period 1
STARTED	29	30	33
COMPLETED	29	29	33
NOT COMPLETED	0	1	0
Period Title: Treatment Period 1
STARTED	29	29	33
COMPLETED	29	29	33
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Cross over study with 3 Arms. (1)Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily. (2)Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily. (3) Placebo, 1 inhalation twice daily
Overall Participants	111
Age (Year) [Mean (Full Range) ]
Mean (Full Range) [Year]	63.7
Sex: Female, Male (Count of Participants)
Female	27 24.3%
Male	84 75.7%

Outcome Measures

1. Primary Outcome

Title	Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 1 Hour Post-dose
Description	Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods.
Time Frame	Single measurement taken1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	96	98	99
Mean (Standard Deviation) [Seconds]	529 (377)	441 (292)	406 (306)

2. Secondary Outcome

Title	Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 6 Hour Post-dose
Description	Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods.
Time Frame	Single measurement taken 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	98	98
Mean (Standard Deviation) [Seconds]	463 (312)	408 (283)	388 (306)

3. Secondary Outcome

Title	Forced Expiratory Flow (FEV1) Pre-dose
Description	The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment.
Time Frame	Pre-dose at the start of treatment and pre-dose after one week of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	101
Mean (Standard Deviation) [Liters]	0.0830 (0.2480)	0.0630 (0.2500)	-0.046 (0.1830)

4. Secondary Outcome

Title	Forced Vital Capacity (FVC) Pre-dose
Description	The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment.
Time Frame	Pre-dose at the start of treatment and pre-dose after one week of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	101
Mean (Standard Deviation) [Liters]	0.060 (0.406)	0.067 (0.407)	-0.094 (0.360)

5. Secondary Outcome

Title	Vital Capacity (VC) Pre-dose (Change From Pre-treatment to Treatment)
Description	The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment.
Time Frame	Pre-dose at the start of treatment and pre-dose after one week of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	101
Mean (Standard Deviation) [Liters]	0.105 (0.3600)	0.089 (0.370)	-0.083 (0.371)

6. Secondary Outcome

Title	Peak Expiratory Flow (PEF) Before Morning Dose
Description	The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period.
Time Frame	Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	97	98	100
Mean (Standard Deviation) [Liters/minute]	1.30 (32.70)	5.60 (21.50)	-10.00 (27.00)

7. Secondary Outcome

Title	Sleep Score
Description	The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (symptoms did not cause a sleep problem) to 4 (did not sleep at all due to symptoms).
Time Frame	Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	98	99	101
Mean (Standard Deviation) [Score on Scale]	-1.70 (0.47)	-0.03 (0.47)	0.11 (0.47)

8. Secondary Outcome

Title	Breathlessness Score
Description	The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any difficulty in breathing) to 4 (almost constant difficulties in breathing). All patients with data from both periods are included.
Time Frame	Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	98	99	101
Mean (Standard Deviation) [Score on Scale]	-0.12 (0.54)	-0.40 (0.46)	0.15 (0.49)

9. Secondary Outcome

Title	Chest Tightness Score
Description	The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any discomfort) to 4 (almost constant discomfort).
Time Frame	Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	98	99	101
Mean (Standard Deviation) [Score on a scale]	-0.08 (0.46)	-0.02 (0.47)	0.17 (0.47)

10. Secondary Outcome

Title	Cough Score
Description	The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of coughing) to 4 (never free of need to cough).
Time Frame	Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	98	99	101
Mean (Standard Deviation) [Scores on a scale]	-0.11 (0.51)	-0.05 (0.50)	0.10 (0.45)

11. Secondary Outcome

Title	Number of Inhalations of Reliever Medication
Description	The change in average daily use for the run-in or wash-out period to the average daily use of the subsequent treatment period.
Time Frame	Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	97	99	101
Mean (Standard Deviation) [Number of inhalations during 24 hours]	-0.42 (1.51)	-0.36 (1.26)	0.51 (1.33)

12. Secondary Outcome

Title	Borg CR10 Score Before Exercise Endurance Time (EET) Performed 1 Hour Post-dose
Description	The Borg CR10 Scale consists of 10-point score that the patients pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness. Patients are allowed to assign an even higher number depending on their perceived level of breathlessness).
Time Frame	Single measurement performed at rest prior to exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	98	98
Mean (Standard Deviation) [Scores on a scale]	3.3 (3.2)	3.4 (3.1)	3.9 (3.5)

13. Secondary Outcome

Title	Borg CR10 Score After Exercise Endurance Time (EET) Performed 1 Hour Post-dose
Description	The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort).
Time Frame	Single measurement performed after exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	98	97
Mean (Standard Deviation) [Scores on a scale]	11.5 (2.7)	11.6 (2.9)	11.4 (2.9)

14. Secondary Outcome

Title	Borg CR10 Score Before Exercise Endurance Time (EET) Performed 6 Hour Post-dose
Description	The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort).
Time Frame	Single measurement performed at rest prior to exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	98	98
Mean (Standard Deviation) [Scores on a scale]	3.6 (3.2)	3.4 (3.1)	3.9 (3.5)

15. Secondary Outcome

Title	Borg CR10 Score After Exercise Endurance Time (EET) Performed 6 Hours Post-dose
Description	The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). All patients with data are included.
Time Frame	Single measurement performed after exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	94	98	96
Mean (Standard Deviation) [Scores on a scale]	11.5 (2.9)	11.5 (3.1)	11.8 (3.1)

16. Secondary Outcome

Title	Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 1 Hour Postdose
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	72	78	70
Mean (Standard Deviation) [Liter]	2.06 (0.85)	2.10 (0.82)	1.97 (0.72)

17. Secondary Outcome

Title	Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	71	78	76
Mean (Standard Deviation) [Liters]	2.12 (0.79)	2.12 (0.80)	1.85 (0.84)

18. Secondary Outcome

Title	Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	96	99	102
Mean (Standard Deviation) [Liters]	2.75 (0.72)	2.73 (0.77)	2.37 (0.66)

19. Secondary Outcome

Title	Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	96	99	102
Mean (Standard Deviation) [Liters]	2.19 (0.61)	2.18 (0.70)	1.91 (0.58)

20. Secondary Outcome

Title	Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	96	99	102
Median (Standard Deviation) [Liters]	5.59 (1.69)	5.66 (1.61)	5.79 (1.64)

21. Secondary Outcome

Title	Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	102
Mean (Standard Deviation) [Liters]	4.83 (1.59)	4.94 (1.62)	5.13 (1.65)

22. Secondary Outcome

Title	Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	96	99	102
Mean (Standard Deviation) [Liter]	7.58 (1.71)	7.62 (1.68)	7.45 (1.76)

23. Secondary Outcome

Title	Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	96	99	101
Mean (Standard Deviation) [kilopascal]	2.90 (1.66)	2.98 (1.81)	4.22 (2.29)

24. Secondary Outcome

Title	Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	100
Mean (Standard Deviation) [Liters]	2.69 (0.730)	2.64 (0.78)	2.42 (0.71)

25. Secondary Outcome

Title	Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	100
Mean (Standard Deviation) [Liters]	2.14 (0.60)	2.08 (0.69)	1.92 (0.66)

26. Secondary Outcome

Title	Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	94	99	99
Mean (Standard Deviation) [Liters]	5.47 (1.65)	5.49 (1.45)	5.82 (1.88)

27. Secondary Outcome

Title	Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hous post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	94	99	99
Mean (Standard Deviation) [Liters]	4.74 (1.63)	4.79 (1.52)	5.19 (1.92)

28. Secondary Outcome

Title	Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	94	99	100
Mean (Standard Deviation) [Liters]	7.41 (1.68)	7.37 (1.55)	7.63 (2.00)

29. Secondary Outcome

Title	Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET
Description	Treatment means from individual participant data.
Time Frame	Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	95	99	100
Mean (Standard Deviation) [Kilopascals]	3.06 (1.68)	3.20 (2.02)	4.12 (2.54)

30. Secondary Outcome

Title	SGRQ-C (St. George's Respiratory Questionnaire for COPD Patients) Total Score
Description	Score from a questionnaire, with scores ranging form 0 (perfect health) to 100 (worst possible state). Includes all patients with data.
Time Frame	Single measurement taken at the end of each 1-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Symbicort	Formoterol	Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo, 1 inhalation twice daily
Measure Participants	85	93	91
Mean (Standard Deviation) [Scores on a scale]	51.7 (18)	51.6 (19.2)	54.5 (18.9)

Adverse Events

Arm/Group Title	Symbicort		Formoterol		Placebo
Arm/Group Description	Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily		Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily		Placebo, 1 inhalation twice daily
All Cause Mortality
	Symbicort		Formoterol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Symbicort		Formoterol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/101 (2%)		1/102 (1%)		1/104 (1%)
Injury, poisoning and procedural complications
Wrist Fracture	1/101 (1%)		0/102 (0%)		0/104 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/101 (1%)		1/102 (1%)		1/104 (1%)
Other (Not Including Serious) Adverse Events
	Symbicort		Formoterol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/101 (4%)		3/102 (2.9%)		6/104 (5.8%)
Respiratory, thoracic and mediastinal disorders
Chonic Obstructive Pulmonary Disease	4/101 (4%)		3/102 (2.9%)		6/104 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Prior to any publication or disclosure, the PI provides AstraZeneca with preliminary data and drafts and with the proposed final manuscript. AstraZeneca shall have a period of 30 days from receipt of the proposed final manuscript to review it and may within such time frame require that submission for publication or disclosure be delayed.