Trial Outcomes & Findings for Efficacy and Tolerability of Symbicort as an add-on Treatment to Spiriva Compare With Spiriva Alone in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01397890)

NCT ID: NCT01397890

Last Updated: 2015-03-27

Results Overview

Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 793 participants
• Primary outcome timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
• Results posted on: 2015-03-27

Participant Flow

There are 793 patients enrolled. 578 patients were randomized, where there are 287 patients randomized in Symbicort+ Spiriva group and 291 in Spiriva group

Participant milestones

Measure	Symbicort+Spiriva Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Study STARTED	287	291
Overall Study Post-baseline Efficacy Data Collected	287	290
Overall Study Received Correct Randomized Treatment	286	287
Overall Study COMPLETED	264	260
Overall Study NOT COMPLETED	23	31

Reasons for withdrawal

Measure	Symbicort+Spiriva Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Study Withdrawal by Subject	7	11
Overall Study Eligibility Criteria Not Fulfilled	7	6
Overall Study Death	2	3
Overall Study Lost to Follow-up	1	4
Overall Study Condition under Investigation Worsened	1	3
Overall Study Adverse Event	1	2
Overall Study Severe Non-Compliance to Protocol	2	1
Overall Study Others	2	1

Baseline Characteristics

Efficacy and Tolerability of Symbicort as an add-on Treatment to Spiriva Compare With Spiriva Alone in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	Symbicort+Spiriva n=287 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=290 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily	Total n=577 Participants Total of all reporting groups
Age, Continuous	66.6 Years STANDARD_DEVIATION 7.99 • n=5 Participants	66.9 Years STANDARD_DEVIATION 8.50 • n=7 Participants	66.8 Years STANDARD_DEVIATION 8.25 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	17 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	279 Participants n=5 Participants	273 Participants n=7 Participants	552 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=284 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=277 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Pre-dose FEV1	1.050 Ratio Interval 1.03 to 1.07	1.006 Ratio Interval 0.987 to 1.025

SECONDARY outcome

Timeframe: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of post-dose FEV1 at 5 minutes to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=287 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose FEV1 at 5 Minutes	1.128 Ratio Interval 1.109 to 1.147	1.045 Ratio Interval 1.028 to 1.062

SECONDARY outcome

Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of post-dose FEV1 at 60 minutes to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=287 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose FEV1 at 60 Minutes	1.164 Ratio Interval 1.144 to 1.185	1.072 Ratio Interval 1.053 to 1.091

SECONDARY outcome

Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=284 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=277 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Pre-dose FVC	1.032 Ratio Interval 1.017 to 1.047	1.013 Ratio Interval 0.999 to 1.029

SECONDARY outcome

Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of post-dose FVC at 5 minutes to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=287 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose FVC at 5 Minutes	1.096 Ratio Interval 1.081 to 1.11	1.044 Ratio Interval 1.03 to 1.057

SECONDARY outcome

Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of post-dose FVC at 60 minutes to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=287 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose FVC at 60 Minutes	1.116 Ratio Interval 1.1 to 1.132	1.059 Ratio Interval 1.044 to 1.074

SECONDARY outcome

Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=265 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=263 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Pre-dose IC	1.042 Ratio Interval 1.017 to 1.068	1.022 Ratio Interval 0.998 to 1.047

SECONDARY outcome

Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Ratio of post-dose IC at 60 minutes to baseline value

Outcome measures

Measure	Symbicort+Spiriva n=263 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=270 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose IC at 60 Minutes	1.154 Ratio Interval 1.129 to 1.18	1.087 Ratio Interval 1.064 to 1.11

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment, up to 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment

Outcome measures

Measure	Symbicort+Spiriva n=217 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=208 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Pre-dose PEF in Last Week of Treatment	15.753 L/min Interval 7.306 to 24.2	-4.550 L/min Interval -13.154 to 4.054

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the first week of treatment

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of treatment

Outcome measures

Measure	Symbicort+Spiriva n=239 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=241 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Pre-dose PEF in First Week of Treatment	13.405 L/min Interval 8.464 to 18.345	-0.182 L/min Interval -4.994 to 4.63

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in pre-dose morning PEF from run-in period to whole treatment period

Outcome measures

Measure	Symbicort+Spiriva n=256 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=262 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Pre-dose PEF in Whole Treatment Period	12.271 L/min Interval 6.382 to 18.16	-5.198 L/min Interval -10.925 to 0.53

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment, up to 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment

Outcome measures

Measure	Symbicort+Spiriva n=177 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=162 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose PEF in Last Week of Treatment	23.379 L/min Interval 13.199 to 33.56	-3.049 L/min Interval -13.556 to 7.458

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the first week of treatment

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment

Outcome measures

Measure	Symbicort+Spiriva n=186 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=201 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose PEF in First Week of Treatment	17.412 L/min Interval 9.349 to 25.476	0.220 L/min Interval -7.486 to 7.926

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period

Outcome measures

Measure	Symbicort+Spiriva n=248 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=247 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Post-dose PEF in Whole Treatment Period	15.880 L/min Interval 9.307 to 22.454	-2.591 L/min Interval -9.063 to 3.88

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in the number of inhalations of reliever medication during day from run-in period to the last week on treatment

Outcome measures

Measure	Symbicort+Spiriva n=274 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=274 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Use of Reliever Medication During Day in the Last Week on Treatment	-0.750 times/day Interval -0.935 to 0.566	-0.082 times/day Interval -0.267 to 0.103

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment

Outcome measures

Measure	Symbicort+Spiriva n=284 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=284 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Use of Reliever Medication During Day in the First Week on Treatment	-0.457 times/day Interval -0.598 to -0.316	-0.082 times/day Interval -0.222 to 0.058

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period

Outcome measures

Measure	Symbicort+Spiriva n=284 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Use of Reliever Medication During Day in the Whole Treatment Period	-0.685 times/day Interval -0.836 to -0.533	-0.134 times/day Interval -0.284 to 0.016

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment

Outcome measures

Measure	Symbicort+Spiriva n=272 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=275 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Use of Reliever Medication During Night in the Last Week on Treatment	-0.174 times/day Interval -0.299 to -0.049	0.062 times/day Interval -0.062 to 0.187

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment

Outcome measures

Measure	Symbicort+Spiriva n=283 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Use of Reliever Medication During Night in the First Week on Treatment	-0.113 times/day Interval -0.206 to -0.019	0.011 times/day Interval -0.081 to 0.104

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in the number of inhalations of reliever medication during night from run-in period to the whole treatment period

Outcome measures

Measure	Symbicort+Spiriva n=285 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Use of Reliever Medication During Night in the Whole Treatment Period	-0.241 times/day Interval -0.336 to -0.147	-0.010 times/day Interval -0.104 to 0.084

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in breathing symptom score (from 0:none to 4:severe) from run-in period

Outcome measures

Measure	Symbicort+Spiriva n=284 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Change in COPD Symptoms - Breathing	-0.372 score on a scale Interval -0.454 to -0.29	-0.110 score on a scale Interval -0.191 to -0.029

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in Cough symptom score (from 0:none to 4:severe) from run-in period

Outcome measures

Measure	Symbicort+Spiriva n=283 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Change in COPD Symptoms - Cough	-0.311 score on a scale Interval -0.394 to -0.229	-0.169 score on a scale Interval -0.25 to -0.087

SECONDARY outcome

Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Change in Sputum symptom score (from 0:none to 4:severe) from run-in period

Outcome measures

Measure	Symbicort+Spiriva n=284 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=286 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
Change in COPD Symptoms - Sputum	-0.216 score on a scale Interval -0.295 to -0.136	-0.094 score on a scale Interval -0.173 to -0.014

SECONDARY outcome

Timeframe: Whole treatment period of 12 weeks

Population: FAS (287 + 290); less number of patients analyzed was caused by missing values.

Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms

Outcome measures

Measure	Symbicort+Spiriva n=287 Participants Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=290 Participants Spiriva 18 μg/inhalation, 1 inhalation once daily
COPD Exacerbations	0.182 exacerbations/participant/12 weeks Interval 0.138 to 0.239	0.307 exacerbations/participant/12 weeks Interval 0.248 to 0.379

Adverse Events

Symbicort+Spiriva

Serious events: 14 serious events

Other events: 75 other events

Deaths: 0 deaths

Spiriva

Serious events: 24 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Measure	Symbicort+Spiriva n=289 participants at risk Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=289 participants at risk Spiriva 18 μg/inhalation, 1 inhalation once daily
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.4% 7/289 • Number of events 7 • 12 weeks of treatment period	4.5% 13/289 • Number of events 13 • 12 weeks of treatment period
Infections and infestations Pneumonia	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	1.4% 4/289 • Number of events 4 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations H1N1 influenza	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Lower respiratory tract infection	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Influenza	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Cardiac disorders Supraventricular tachycardia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Cardiac disorders Cardiac failure congestion	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Gastrointestinal disorders Dyspepsia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Gastrointestinal disorders Gastroenteritis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
General disorders Death	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Hepatobiliary disorders Bile duct cancer	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Nervous system disorders Presyncope	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Joint dislocation	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period

Other adverse events

Measure	Symbicort+Spiriva n=289 participants at risk Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)	Spiriva n=289 participants at risk Spiriva 18 μg/inhalation, 1 inhalation once daily
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	2.1% 6/289 • Number of events 6 • 12 weeks of treatment period	4.5% 13/289 • Number of events 13 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Cough	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	2.4% 7/289 • Number of events 7 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Rhonchi	0.00% 0/289 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Bronchitis	1.7% 5/289 • Number of events 5 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Sputum increased	1.7% 5/289 • Number of events 5 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Chest discomfort	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Chest pain	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Dry throat	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Dysphonia	1.7% 5/289 • Number of events 5 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Respiratory, thoracic and mediastinal disorders Productive cough	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Gastrointestinal disorders Dry mouth	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period	1.4% 4/289 • Number of events 4 • 12 weeks of treatment period
Gastrointestinal disorders Dyspepsia	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period
Gastrointestinal disorders Constipation	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Gastrointestinal disorders Gastritis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Gastrointestinal disorders Abdominal discomfort	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Gastrointestinal disorders Abdominal distension	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Gastrointestinal disorders Dysphagia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Gastrointestinal disorders Faecal incontinence	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Gastrointestinal disorders Stomatitis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Gastrointestinal disorders Aphthous stomatitis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Gastrointestinal disorders Colon adenoma	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Gastrointestinal disorders Diarrhoea	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Gastrointestinal disorders Gastroenteritis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Gastrointestinal disorders Gingival oedema	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Infections and infestations Oral candidiasis	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period
Infections and infestations Upper respiratory tract infection	1.7% 5/289 • Number of events 5 • 12 weeks of treatment period	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period
Infections and infestations Herpes zoster	0.00% 0/289 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Infections and infestations Lower respiratory tract infection	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Candidiasis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Influenza	1.4% 4/289 • Number of events 4 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Pharyngitis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Post herpetic neuralgia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Infections and infestations Urinary tract infection	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Nervous system disorders Headache	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	1.4% 4/289 • Number of events 4 • 12 weeks of treatment period
Nervous system disorders Dementia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Nervous system disorders Dizziness	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Nervous system disorders Lumbar radiculopathy	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Skin and subcutaneous tissue disorders Dermatitis	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	1.0% 3/289 • Number of events 3 • 12 weeks of treatment period
Skin and subcutaneous tissue disorders Rash	0.00% 0/289 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Skin and subcutaneous tissue disorders Eczema	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Skin and subcutaneous tissue disorders Pruritus	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Skin and subcutaneous tissue disorders Skin irritation	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
General disorders Chest pain	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
General disorders Gait disturbance	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
General disorders Oedema	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
General disorders Oedema peripheral	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
General disorders Pyrexia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
General disorders Chills	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
General disorders Influenza like illness	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Arthralgia	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Myalgia	2.1% 6/289 • Number of events 6 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Spondylitis	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Back pain	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Fracture	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Musculoskeletal and connective tissue disorders Muscle spasms	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Hepatobiliary disorders Hyperplastic cholecystopathy	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Injury, poisoning and procedural complications Open wound	0.69% 2/289 • Number of events 2 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Injury, poisoning and procedural complications Muscle strain	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Investigations Sputum abnormal	0.00% 0/289 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Reproductive system and breast disorders Benign prostatic hyperplasia	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period
Blood and lymphatic system disorders Eosinophilia	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period
Vascular disorders Hypertension	0.35% 1/289 • Number of events 1 • 12 weeks of treatment period	0.00% 0/289 • 12 weeks of treatment period

Additional Information

Nongluk Yimsuan

AstraZeneca

Phone: 66 2 7397400

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PI Disclosure Restriction is indicated in the Clinical Study Agreement, please refer to this document of each PI and country.
• Publication restrictions are in place

Restriction type: OTHER