Trial Outcomes & Findings for Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD (NCT NCT00489853)

NCT ID: NCT00489853

Last Updated: 2012-08-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 137 participants
• Primary outcome timeframe: Single measurement taken1 hour post-dose at the end of each 1-week treatment period
• Results posted on: 2012-08-30

Participant Flow

Patients were recruited in 12 centers in Germany and 12 centers in Switzerland.

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.)

Participant milestones

Measure	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	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	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
Treatment Period 1 STARTED	36	37	38
Treatment Period 1 COMPLETED	36	37	38
Treatment Period 1 NOT COMPLETED	0	0	0
Wash-out Period 1 STARTED	36	37	38
Wash-out Period 1 COMPLETED	35	34	32
Wash-out Period 1 NOT COMPLETED	1	3	6
Treatment Period 2 STARTED	33	35	33
Treatment Period 2 COMPLETED	33	35	33
Treatment Period 2 NOT COMPLETED	0	0	0
Wash-out Period 2 STARTED	33	35	33
Wash-out Period 2 COMPLETED	29	32	31
Wash-out Period 2 NOT COMPLETED	4	3	2
Treatment Period 3 STARTED	29	30	33
Treatment Period 3 COMPLETED	29	29	33
Treatment Period 3 NOT COMPLETED	0	1	0
Follow-up Period STARTED	29	29	33
Follow-up Period COMPLETED	29	29	33
Follow-up Period NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	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	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	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
Wash-out Period 1 Withdrawal by Subject	1	0	0
Wash-out Period 1 Adverse Event	0	1	1
Wash-out Period 1 Protocol Violation	0	1	1
Wash-out Period 1 Study-specific discontinuation criteria	0	1	4
Wash-out Period 2 Adverse Event	1	1	0
Wash-out Period 2 Study specific discontinuation criteria	3	2	2
Treatment Period 3 Study specific discontinuation criteria	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Entire Study Population n=111 Participants 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
Age Continuous	63.7 Year n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	84 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=96 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=99 Participants Placebo, 1 inhalation twice daily
Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 1 Hour Post-dose	529 Seconds Standard Deviation 377	441 Seconds Standard Deviation 292	406 Seconds Standard Deviation 306

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=98 Participants Placebo, 1 inhalation twice daily
Exercise Endurance Time (EET) at 75% of Peak Work Capacity With Cycle Ergometry 6 Hour Post-dose	463 Seconds Standard Deviation 312	408 Seconds Standard Deviation 283	388 Seconds Standard Deviation 306

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Forced Expiratory Flow (FEV1) Pre-dose	0.0830 Liters Standard Deviation 0.2480	0.0630 Liters Standard Deviation 0.2500	-0.046 Liters Standard Deviation 0.1830

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Forced Vital Capacity (FVC) Pre-dose	0.060 Liters Standard Deviation 0.406	0.067 Liters Standard Deviation 0.407	-0.094 Liters Standard Deviation 0.360

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Vital Capacity (VC) Pre-dose (Change From Pre-treatment to Treatment)	0.105 Liters Standard Deviation 0.3600	0.089 Liters Standard Deviation 0.370	-0.083 Liters Standard Deviation 0.371

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=97 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=100 Participants Placebo, 1 inhalation twice daily
Peak Expiratory Flow (PEF) Before Morning Dose	1.30 Liters/minute Standard Deviation 32.70	5.60 Liters/minute Standard Deviation 21.50	-10.00 Liters/minute Standard Deviation 27.00

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Symbicort n=98 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Sleep Score	-1.70 Score on Scale Standard Deviation 0.47	-0.03 Score on Scale Standard Deviation 0.47	0.11 Score on Scale Standard Deviation 0.47

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=98 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Breathlessness Score	-0.12 Score on Scale Standard Deviation 0.54	-0.40 Score on Scale Standard Deviation 0.46	0.15 Score on Scale Standard Deviation 0.49

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Symbicort n=98 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Chest Tightness Score	-0.08 Score on a scale Standard Deviation 0.46	-0.02 Score on a scale Standard Deviation 0.47	0.17 Score on a scale Standard Deviation 0.47

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Symbicort n=98 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Cough Score	-0.11 Scores on a scale Standard Deviation 0.51	-0.05 Scores on a scale Standard Deviation 0.50	0.10 Scores on a scale Standard Deviation 0.45

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=97 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Number of Inhalations of Reliever Medication	-0.42 Number of inhalations during 24 hours Standard Deviation 1.51	-0.36 Number of inhalations during 24 hours Standard Deviation 1.26	0.51 Number of inhalations during 24 hours Standard Deviation 1.33

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=98 Participants Placebo, 1 inhalation twice daily
Borg CR10 Score Before Exercise Endurance Time (EET) Performed 1 Hour Post-dose	3.3 Scores on a scale Standard Deviation 3.2	3.4 Scores on a scale Standard Deviation 3.1	3.9 Scores on a scale Standard Deviation 3.5

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=97 Participants Placebo, 1 inhalation twice daily
Borg CR10 Score After Exercise Endurance Time (EET) Performed 1 Hour Post-dose	11.5 Scores on a scale Standard Deviation 2.7	11.6 Scores on a scale Standard Deviation 2.9	11.4 Scores on a scale Standard Deviation 2.9

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=98 Participants Placebo, 1 inhalation twice daily
Borg CR10 Score Before Exercise Endurance Time (EET) Performed 6 Hour Post-dose	3.6 Scores on a scale Standard Deviation 3.2	3.4 Scores on a scale Standard Deviation 3.1	3.9 Scores on a scale Standard Deviation 3.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=94 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=98 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=96 Participants Placebo, 1 inhalation twice daily
Borg CR10 Score After Exercise Endurance Time (EET) Performed 6 Hours Post-dose	11.5 Scores on a scale Standard Deviation 2.9	11.5 Scores on a scale Standard Deviation 3.1	11.8 Scores on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=72 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=78 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=70 Participants Placebo, 1 inhalation twice daily
Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 1 Hour Postdose	2.06 Liter Standard Deviation 0.85	2.10 Liter Standard Deviation 0.82	1.97 Liter Standard Deviation 0.72

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=71 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=78 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=76 Participants Placebo, 1 inhalation twice daily
Inspiratory Capacity (IC) Before Exercise Endurance Time (EET) Performed 6 Hours Post-dose	2.12 Liters Standard Deviation 0.79	2.12 Liters Standard Deviation 0.80	1.85 Liters Standard Deviation 0.84

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=96 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=102 Participants Placebo, 1 inhalation twice daily
Vital Capacity (VC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)	2.75 Liters Standard Deviation 0.72	2.73 Liters Standard Deviation 0.77	2.37 Liters Standard Deviation 0.66

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=96 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=102 Participants Placebo, 1 inhalation twice daily
Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)	2.19 Liters Standard Deviation 0.61	2.18 Liters Standard Deviation 0.70	1.91 Liters Standard Deviation 0.58

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=96 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=102 Participants Placebo, 1 inhalation twice daily
Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)	5.59 Liters Standard Deviation 1.69	5.66 Liters Standard Deviation 1.61	5.79 Liters Standard Deviation 1.64

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=102 Participants Placebo, 1 inhalation twice daily
Residual Volume (RV) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)	4.83 Liters Standard Deviation 1.59	4.94 Liters Standard Deviation 1.62	5.13 Liters Standard Deviation 1.65

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=96 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=102 Participants Placebo, 1 inhalation twice daily
Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 1 Hour Exercise Endurance Time (EET)	7.58 Liter Standard Deviation 1.71	7.62 Liter Standard Deviation 1.68	7.45 Liter Standard Deviation 1.76

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=96 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=101 Participants Placebo, 1 inhalation twice daily
Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 1 Hour Post-dose Exercise Endurance Time (EET)	2.90 kilopascal Standard Deviation 1.66	2.98 kilopascal Standard Deviation 1.81	4.22 kilopascal Standard Deviation 2.29

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=100 Participants Placebo, 1 inhalation twice daily
Vital Capacity (VC) (Body Plethysmography) Performed Before 6 Hour Exercise Endurance Time (EET)	2.69 Liters Standard Deviation 0.730	2.64 Liters Standard Deviation 0.78	2.42 Liters Standard Deviation 0.71

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=100 Participants Placebo, 1 inhalation twice daily
Inspiratory Capacity (IC) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)	2.14 Liters Standard Deviation 0.60	2.08 Liters Standard Deviation 0.69	1.92 Liters Standard Deviation 0.66

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=94 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=99 Participants Placebo, 1 inhalation twice daily
Forced Respiratory Capacity (FRC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)	5.47 Liters Standard Deviation 1.65	5.49 Liters Standard Deviation 1.45	5.82 Liters Standard Deviation 1.88

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=94 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=99 Participants Placebo, 1 inhalation twice daily
Residual Volume (RV) (Body Plethysmography) Performed Before 6 Hour Post-dose Exercise Endurance Time (EET)	4.74 Liters Standard Deviation 1.63	4.79 Liters Standard Deviation 1.52	5.19 Liters Standard Deviation 1.92

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=94 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=100 Participants Placebo, 1 inhalation twice daily
Total Lung Capacity (TLC) (Body Plethysmography) Performed Before 6 Hours Post-dose Exercise Endurance Time (EET)	7.41 Liters Standard Deviation 1.68	7.37 Liters Standard Deviation 1.55	7.63 Liters Standard Deviation 2.00

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=95 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=99 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=100 Participants Placebo, 1 inhalation twice daily
Specific Airway Resistance (sRaw) (Body Plethysmography) Performed Before 6 Hours Post-dose EET	3.06 Kilopascals Standard Deviation 1.68	3.20 Kilopascals Standard Deviation 2.02	4.12 Kilopascals Standard Deviation 2.54

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Symbicort n=85 Participants Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=93 Participants Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=91 Participants Placebo, 1 inhalation twice daily
SGRQ-C (St. George's Respiratory Questionnaire for COPD Patients) Total Score	51.7 Scores on a scale Standard Deviation 18	51.6 Scores on a scale Standard Deviation 19.2	54.5 Scores on a scale Standard Deviation 18.9

Adverse Events

Symbicort

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Formoterol

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Symbicort n=101 participants at risk Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=102 participants at risk Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=104 participants at risk Placebo, 1 inhalation twice daily
Injury, poisoning and procedural complications Wrist Fracture	0.99% 1/101	0.00% 0/102	0.00% 0/104
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.99% 1/101	0.98% 1/102	0.96% 1/104

Other adverse events

Measure	Symbicort n=101 participants at risk Symbicort (budesonide/formoterol) Turbuhaler 320/9 micrograms, 1 inhalation twice daily	Formoterol n=102 participants at risk Formoterol Turbuhaler 9 micrograms, 1 inhalation twice daily	Placebo n=104 participants at risk Placebo, 1 inhalation twice daily
Respiratory, thoracic and mediastinal disorders Chonic Obstructive Pulmonary Disease	4.0% 4/101	2.9% 3/102	5.8% 6/104

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

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

Restriction type: OTHER