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Trial record 56 of 183 for:    Foradil Combi OR symbicort OR (Budesonide AND formeterol)

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) (SECURE 1)

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ClinicalTrials.gov Identifier: NCT01397890
Recruitment Status : Completed
First Posted : July 20, 2011
Results First Posted : August 27, 2014
Last Update Posted : March 27, 2015
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: Budesonide/formoterol (Symbicort® Turbuhaler®)
Drug: Tiotropium (SpirivaTM)
Enrollment 793
Recruitment Details There are 793 patients enrolled. 578 patients were randomized, where there are 287 patients randomized in Symbicort+ Spiriva group and 291 in Spiriva group
Pre-assignment Details  
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily) Spiriva 18 μg/inhalation, 1 inhalation once daily
Period Title: Overall Study
Started 287 291
Post-baseline Efficacy Data Collected 287 [1] 290 [1]
Received Correct Randomized Treatment 286 [2] 287 [3]
Completed 264 260
Not Completed 23 31
Reason Not Completed
Withdrawal by Subject             7             11
Eligibility Criteria Not Fulfilled             7             6
Death             2             3
Lost to Follow-up             1             4
Condition under Investigation Worsened             1             3
Adverse Event             1             2
Severe Non-Compliance to Protocol             2             1
Others             2             1
[1]
'Full Analysis Set' used for efficacy analysis
[2]
'Safety Analysis Set' =287+3-1=289. 3 and 1 pts in respective groups received opposite treatment.
[3]
'Safety Analysis Set' =291+1-3=289.
Arm/Group Title Symbicort+Spiriva Spiriva Total
Hide Arm/Group Description Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily) Spiriva 18 μg/inhalation, 1 inhalation once daily Total of all reporting groups
Overall Number of Baseline Participants 287 290 577
Hide Baseline Analysis Population Description
Overall Number of Baseline Participants is not different from the Milestones.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 287 participants 290 participants 577 participants
66.6  (7.99) 66.9  (8.50) 66.8  (8.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 290 participants 577 participants
Female
8
   2.8%
17
   5.9%
25
   4.3%
Male
279
  97.2%
273
  94.1%
552
  95.7%
1.Primary Outcome
Title Pre-dose FEV1
Hide Description Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value
Time Frame Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 284 277
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.050
(1.030 to 1.070)
1.006
(0.987 to 1.025)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments multiplicative ANCOVA model with treatment and country as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.044
Confidence Interval (2-Sided) 95%
1.019 to 1.069
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Post-dose FEV1 at 5 Minutes
Hide Description Ratio of post-dose FEV1 at 5 minutes to baseline value
Time Frame Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 287 286
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.128
(1.109 to 1.147)
1.045
(1.028 to 1.062)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.079
Confidence Interval (2-Sided) 95%
1.057 to 1.102
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Post-dose FEV1 at 60 Minutes
Hide Description Ratio of post-dose FEV1 at 60 minutes to baseline value
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 287 286
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.164
(1.144 to 1.185)
1.072
(1.053 to 1.091)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.086
Confidence Interval (2-Sided) 95%
1.062 to 1.111
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Pre-dose FVC
Hide Description Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 284 277
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.032
(1.017 to 1.047)
1.013
(0.999 to 1.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0570
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.018
Confidence Interval (2-Sided) 95%
0.999 to 1.037
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Post-dose FVC at 5 Minutes
Hide Description Ratio of post-dose FVC at 5 minutes to baseline value
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 287 286
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.096
(1.081 to 1.110)
1.044
(1.030 to 1.057)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.050
Confidence Interval (2-Sided) 95%
1.033 to 1.067
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Post-dose FVC at 60 Minutes
Hide Description Ratio of post-dose FVC at 60 minutes to baseline value
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 287 286
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.116
(1.100 to 1.132)
1.059
(1.044 to 1.074)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.054
Confidence Interval (2-Sided) 95%
1.036 to 1.073
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Pre-dose IC
Hide Description Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value
Time Frame Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 265 263
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.042
(1.017 to 1.068)
1.022
(0.998 to 1.047)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1956
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.020
Confidence Interval (2-Sided) 95%
0.990 to 1.050
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Post-dose IC at 60 Minutes
Hide Description Ratio of post-dose IC at 60 minutes to baseline value
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 263 270
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.154
(1.129 to 1.180)
1.087
(1.064 to 1.110)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and country as fixed factors and week 0 pre-dose value as a (log-transformed) covariate.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.062
Confidence Interval (2-Sided) 95%
1.035 to 1.091
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Pre-dose PEF in Last Week of Treatment
Hide Description Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 217 208
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
15.753
(7.306 to 24.200)
-4.550
(-13.154 to 4.054)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 20.303
Confidence Interval (2-Sided) 95%
9.904 to 30.702
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Pre-dose PEF in First Week of Treatment
Hide Description Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 239 241
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
13.405
(8.464 to 18.345)
-0.182
(-4.994 to 4.630)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13.587
Confidence Interval (2-Sided) 95%
7.407 to 19.766
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Pre-dose PEF in Whole Treatment Period
Hide Description Change in pre-dose morning PEF from run-in period to whole treatment period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 256 262
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
12.271
(6.382 to 18.160)
-5.198
(-10.925 to 0.530)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 17.469
Confidence Interval (2-Sided) 95%
10.147 to 24.791
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Post-dose PEF in Last Week of Treatment
Hide Description Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 177 162
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
23.379
(13.199 to 33.560)
-3.049
(-13.556 to 7.458)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 26.428
Confidence Interval (2-Sided) 95%
13.463 to 39.393
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Post-dose PEF in First Week of Treatment
Hide Description Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 186 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
17.412
(9.349 to 25.476)
0.220
(-7.486 to 7.926)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 17.192
Confidence Interval (2-Sided) 95%
7.491 to 26.894
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Post-dose PEF in Whole Treatment Period
Hide Description Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 248 247
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
15.880
(9.307 to 22.454)
-2.591
(-9.063 to 3.880)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 18.472
Confidence Interval (2-Sided) 95%
10.347 to 26.596
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Use of Reliever Medication During Day in the Last Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during day from run-in period to the last week on treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 274 274
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.750
(-0.935 to 0.566)
-0.082
(-0.267 to 0.103)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.668
Confidence Interval (2-Sided) 95%
-0.900 to -0.437
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Use of Reliever Medication During Day in the First Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 284 284
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.457
(-0.598 to -0.316)
-0.082
(-0.222 to 0.058)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.375
Confidence Interval (2-Sided) 95%
-0.552 to -0.198
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Use of Reliever Medication During Day in the Whole Treatment Period
Hide Description Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 284 286
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.685
(-0.836 to -0.533)
-0.134
(-0.284 to 0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.551
Confidence Interval (2-Sided) 95%
-0.741 to -0.361
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Use of Reliever Medication During Night in the Last Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 272 275
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.174
(-0.299 to -0.049)
0.062
(-0.062 to 0.187)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.236
Confidence Interval (2-Sided) 95%
-0.391 to -0.082
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Use of Reliever Medication During Night in the First Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 283 286
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.113
(-0.206 to -0.019)
0.011
(-0.081 to 0.104)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0372
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.124
Confidence Interval (2-Sided) 95%
-0.240 to -0.007
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Use of Reliever Medication During Night in the Whole Treatment Period
Hide Description Change in the number of inhalations of reliever medication during night from run-in period to the whole treatment period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 285 286
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.241
(-0.336 to -0.147)
-0.010
(-0.104 to 0.084)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.231
Confidence Interval (2-Sided) 95%
-0.350 to -0.113
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change in COPD Symptoms - Breathing
Hide Description Change in breathing symptom score (from 0:none to 4:severe) from run-in period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 284 286
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-0.372
(-0.454 to -0.290)
-0.110
(-0.191 to -0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.262
Confidence Interval (2-Sided) 95%
-0.364 to -0.159
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change in COPD Symptoms - Cough
Hide Description Change in Cough symptom score (from 0:none to 4:severe) from run-in period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 283 286
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-0.311
(-0.394 to -0.229)
-0.169
(-0.250 to -0.087)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.143
Confidence Interval (2-Sided) 95%
-0.246 to -0.040
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change in COPD Symptoms - Sputum
Hide Description Change in Sputum symptom score (from 0:none to 4:severe) from run-in period
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 284 286
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-0.216
(-0.295 to -0.136)
-0.094
(-0.173 to -0.014)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0171
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.122
Confidence Interval (2-Sided) 95%
-0.222 to -0.022
Estimation Comments [Not Specified]
24.Secondary Outcome
Title COPD Exacerbations
Hide Description Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms
Time Frame Whole treatment period of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (287 + 290); less number of patients analyzed was caused by missing values.
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description:
Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily)
Spiriva 18 μg/inhalation, 1 inhalation once daily
Overall Number of Participants Analyzed 287 290
Least Squares Mean (95% Confidence Interval)
Unit of Measure: exacerbations/participant/12 weeks
0.182
(0.138 to 0.239)
0.307
(0.248 to 0.379)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments [Not Specified]
Method Poisson regression
Comments Poisson regression model with treatment as a factor and the duration time in study as an offset variable morning PEF as a covariate
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.593
Confidence Interval (2-Sided) 95%
0.419 to 0.839
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0167
Comments [Not Specified]
Method Regression, Cox
Comments Time to the first COPD exacerbation
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.614
Confidence Interval (2-Sided) 95%
0.412 to 0.916
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Symbicort+Spiriva, Spiriva
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0196
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Time Frame 12 weeks of treatment period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Symbicort+Spiriva Spiriva
Hide Arm/Group Description Budesonide/formoterol (Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to tiotropium (Spiriva 18 μg/inhalation, 1 inhalation once daily) Spiriva 18 μg/inhalation, 1 inhalation once daily
All-Cause Mortality
Symbicort+Spiriva Spiriva
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Symbicort+Spiriva Spiriva
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/289 (4.84%)      24/289 (8.30%)    
Cardiac disorders     
Supraventricular tachycardia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Cardiac failure congestion  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Gastrointestinal disorders     
Dyspepsia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Gastroenteritis  1  1/289 (0.35%)  1 0/289 (0.00%)  0
General disorders     
Death  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Hepatobiliary disorders     
Bile duct cancer  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Infections and infestations     
Pneumonia  1  2/289 (0.69%)  2 4/289 (1.38%)  4
H1N1 influenza  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Lower respiratory tract infection  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Influenza  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Hypoglycaemia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Musculoskeletal and connective tissue disorders     
Joint dislocation  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Spinal column stenosis  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastric cancer  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Metastases to bone  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Metastatic renal cell carcinoma  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Nervous system disorders     
Presyncope  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  7/289 (2.42%)  7 13/289 (4.50%)  13
Dyspnoea  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Pulmonary oedema  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Symbicort+Spiriva Spiriva
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   75/289 (25.95%)      76/289 (26.30%)    
Blood and lymphatic system disorders     
Eosinophilia * 1  1/289 (0.35%)  1 0/289 (0.00%)  0
Gastrointestinal disorders     
Dry mouth  1  3/289 (1.04%)  3 4/289 (1.38%)  4
Dyspepsia  1  2/289 (0.69%)  2 3/289 (1.04%)  3
Constipation  1  1/289 (0.35%)  1 2/289 (0.69%)  2
Gastritis  1  1/289 (0.35%)  1 2/289 (0.69%)  2
Abdominal discomfort  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Abdominal distension  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Dysphagia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Faecal incontinence  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Stomatitis  1  1/289 (0.35%)  1 1/289 (0.35%)  1
Aphthous stomatitis  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Colon adenoma  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Diarrhoea  1  2/289 (0.69%)  2 0/289 (0.00%)  0
Gastroenteritis  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Gingival oedema  1  1/289 (0.35%)  1 0/289 (0.00%)  0
General disorders     
Chest pain  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Gait disturbance  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Oedema  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Oedema peripheral  1  2/289 (0.69%)  2 1/289 (0.35%)  1
Pyrexia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Chills  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Influenza like illness  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Hepatobiliary disorders     
Hyperplastic cholecystopathy * 1  1/289 (0.35%)  1 0/289 (0.00%)  0
Infections and infestations     
Oral candidiasis  1  3/289 (1.04%)  3 3/289 (1.04%)  3
Upper respiratory tract infection  1  5/289 (1.73%)  5 3/289 (1.04%)  3
Herpes zoster  1  0/289 (0.00%)  0 2/289 (0.69%)  2
Lower respiratory tract infection  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Candidiasis  1  1/289 (0.35%)  1 1/289 (0.35%)  1
Influenza  1  4/289 (1.38%)  4 1/289 (0.35%)  1
Pharyngitis  1  1/289 (0.35%)  1 1/289 (0.35%)  1
Post herpetic neuralgia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Urinary tract infection  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Injury, poisoning and procedural complications     
Open wound * 1  2/289 (0.69%)  2 1/289 (0.35%)  1
Muscle strain * 1  1/289 (0.35%)  1 0/289 (0.00%)  0
Investigations     
Sputum abnormal * 1  0/289 (0.00%)  0 1/289 (0.35%)  1
Metabolism and nutrition disorders     
Hypoalbuminaemia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Hypokalaemia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Hyponatraemia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/289 (0.35%)  1 2/289 (0.69%)  2
Bursitis  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Joint swelling  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Myalgia  1  6/289 (2.08%)  6 1/289 (0.35%)  1
Spondylitis  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Back pain  1  2/289 (0.69%)  2 0/289 (0.00%)  0
Fracture  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Muscle spasms  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Nervous system disorders     
Headache  1  1/289 (0.35%)  1 4/289 (1.38%)  4
Dementia  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Dizziness  1  2/289 (0.69%)  2 1/289 (0.35%)  1
Lumbar radiculopathy  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  1/289 (0.35%)  1 1/289 (0.35%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Nasopharyngitis  1  6/289 (2.08%)  6 13/289 (4.50%)  13
Cough  1  2/289 (0.69%)  2 7/289 (2.42%)  7
Dyspnoea  1  2/289 (0.69%)  2 3/289 (1.04%)  3
Pharyngitis  1  2/289 (0.69%)  2 3/289 (1.04%)  3
Rhinorrhoea  1  1/289 (0.35%)  1 2/289 (0.69%)  2
Rhonchi  1  0/289 (0.00%)  0 2/289 (0.69%)  2
Bronchitis  1  5/289 (1.73%)  5 1/289 (0.35%)  1
Haemoptysis  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Oropharyngeal pain  1  2/289 (0.69%)  2 1/289 (0.35%)  1
Sputum increased  1  5/289 (1.73%)  5 1/289 (0.35%)  1
Chest discomfort  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Chest pain  1  2/289 (0.69%)  2 0/289 (0.00%)  0
Dry throat  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Dysphonia  1  5/289 (1.73%)  5 0/289 (0.00%)  0
Productive cough  1  2/289 (0.69%)  2 0/289 (0.00%)  0
Skin and subcutaneous tissue disorders     
Dermatitis  1  1/289 (0.35%)  1 3/289 (1.04%)  3
Rash  1  0/289 (0.00%)  0 2/289 (0.69%)  2
Eczema  1  0/289 (0.00%)  0 1/289 (0.35%)  1
Pruritus  1  2/289 (0.69%)  2 1/289 (0.35%)  1
Skin irritation  1  1/289 (0.35%)  1 0/289 (0.00%)  0
Vascular disorders     
Hypertension * 1  1/289 (0.35%)  1 0/289 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The PI Disclosure Restriction is indicated in the Clinical Study Agreement, please refer to this document of each PI and country.
Results Point of Contact
Name/Title: Nongluk Yimsuan
Organization: AstraZeneca
Phone: 66 2 7397400 ext 429
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01397890     History of Changes
Other Study ID Numbers: D589BL00023
First Submitted: June 27, 2011
First Posted: July 20, 2011
Results First Submitted: June 18, 2014
Results First Posted: August 27, 2014
Last Update Posted: March 27, 2015