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Efficacy, Tolerability and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01513460
Recruitment Status : Completed
First Posted : January 20, 2012
Results First Posted : January 5, 2015
Last Update Posted : January 5, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease
Interventions Drug: NVA237 50µg once daily
Drug: Tiotropium 18µg once daily
Drug: Flu/Sal
Drug: NVA237 placebo + Tiotropium placebo.
Enrollment 773
Recruitment Details  
Pre-assignment Details  
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Period Title: Overall Study
Started 258 258 257
Full Analysis Set 257 258 257
Per-protocol Set 196 186 166
Completed 229 226 201
Not Completed 29 32 56
Reason Not Completed
Death             0             0             1
Lost to Follow-up             0             0             2
Abnormal laboratory value             1             0             1
Lack of Efficacy             1             2             5
Protocol deviations             3             4             3
Withdrawal by Subject             7             8             21
Adverse Event             16             18             23
Abnormal test procedure             1             0             0
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal Total
Hide Arm/Group Description NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Total of all reporting groups
Overall Number of Baseline Participants 257 258 257 772
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 257 participants 258 participants 257 participants 772 participants
68.2  (8.38) 68.0  (7.74) 67.8  (8.49) 68.0  (8.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 258 participants 257 participants 772 participants
Female
94
  36.6%
98
  38.0%
83
  32.3%
275
  35.6%
Male
163
  63.4%
160
  62.0%
174
  67.7%
497
  64.4%
1.Primary Outcome
Title Change From Baseline in Mean Trough Forced Expiratory Volume in 1 Second (FEV1) (NVA237 Versus Tiotropium)
Hide Description Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15 hours and 23:45 hours after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45 min and 15 min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.
Time Frame baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the per-protocol set (PPS), who had values at both baseline and week 12, were included in the analysis. The PPS included all randomized participants who had at least one dose of study drug and who were without any major protocol or non-protocol deviations.
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal
Hide Arm/Group Description:
NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Overall Number of Participants Analyzed 194 185
Mean (Standard Error)
Unit of Measure: liters
0.095  (0.0131) 0.102  (0.0135)
2.Secondary Outcome
Title Change From Baseline in Mean Trough FEV1 (Flu/Sal Versus NVA237/Tiotropium+Flu/Sal)
Hide Description Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15h and 23:45h after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45min and 15min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.
Time Frame baseline, 4 weeks, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Flu/Sal NVA237/Tiotropium+Flu/Sal
Hide Arm/Group Description:
Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
NVA237+Flu/Sal and Tiotropium+Flu/Sal arms
Overall Number of Participants Analyzed 257 515
Mean (Standard Error)
Unit of Measure: Liters
Week 4 -0.010  (0.0099) 0.077  (0.0073)
Week 8 -0.002  (0.0099) 0.088  (0.0073)
Week 12 -0.012  (0.0099) 0.088  (0.0073)
3.Secondary Outcome
Title Change From Baseline in Mean Trough FEV1
Hide Description Spirometry was conducted according to internationally accepted standards. Trough FEV1 referred to the mean of FEV1 at 23:15h and 23:45h after the morning dose of study drug. The baseline was defined as the average of FEV1 values taken in the clinic 45min and 15min prior to the first dose of randomized treatment at Visit 3. A mixed model was used and contained treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilators, and FEV1 post-inhalation of bronchodilators and stratification factors as covariates. A positive change from baseline indicates improvement.
Time Frame baseline, 4 weeks, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description:
NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Overall Number of Participants Analyzed 257 258 257
Mean (Standard Error)
Unit of Measure: Liters
Week 4 0.077  (0.0100) 0.077  (0.0101) -0.010  (0.0099)
Week 8 0.084  (0.0100) 0.092  (0.0101) -0.002  (0.0099)
Week 12 0.089  (0.0100) 0.087  (0.0101) -0.012  (0.0099)
4.Secondary Outcome
Title Change From Baseline in Total Score of the St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) After 12 Weeks of Treatment
Hide Description SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest is 100. Higher values corresponded to greater impairment in quality of life. An analysis model included terms for treatment, baseline total SGRQ score, FEV1 and baseline smoking status. The model also contained as fixed effects the baseline total SGRQ score, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator and stratification factors as covariates. A negative change from baseline indicates improvement.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description:
NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Overall Number of Participants Analyzed 257 258 257
Mean (Standard Error)
Unit of Measure: units on a scale
-2.806  (0.6772) -3.902  (0.6920) -0.652  (0.6871)
5.Secondary Outcome
Title Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Use
Hide Description The total number of puffs of rescue medication used over the last 12 h recorded in the morning (nighttime use) and in the evening (daytime use) over the full 12 weeks was divided by the total number of days with non-missing rescue data to derive the mean daytime and nighttime number of puffs of rescue medication. Change from baseline in the mean daytime and nighttime number of puffs of rescue medication was analyzed as for the change from baseline in the mean daily number of puffs of rescue medication.
Time Frame baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description:
NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Overall Number of Participants Analyzed 247 251 241
Mean (Standard Error)
Unit of Measure: puffs of rescue medication
2.191  (0.1384) 2.093  (0.1397) 2.908  (0.1395)
6.Secondary Outcome
Title Mean Percentage of Nights With 'no Nighttime Awakenings'
Hide Description A night with 'no nighttime awakenings' is defined from diary data as any night where patient did not wake up due to symptoms. Total number of nights with 'no nighttime awakenings' over treatment period was divided by total number of nights where diary recordings have been made in order to derive percentage of 'no nighttime awakenings' which will be summarized by treatment and analyzed using a similar mixed model as specified for primary analysis. Diary data recorded during the 7 day run-in period was used to calculate baseline percentage of nights 'no nighttime awakenings'.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description:
NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Overall Number of Participants Analyzed 242 251 239
Mean (Standard Error)
Unit of Measure: Percentage of nights
0.834  (0.0124) 0.816  (0.0124) 0.823  (0.0124)
7.Secondary Outcome
Title Mean Percentage of Days With Performance of Usual Activities
Hide Description A 'day able to perform usual daily activities' was defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' was derived and analyzed using a similar mixed model as specified for primary analysis as for the percentage of nights with 'no nighttime awakenings'.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description:
NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
Overall Number of Participants Analyzed 243 248 237
Mean (Standard Error)
Unit of Measure: Percentage of days
0.934  (0.0087) 0.946  (0.0088) 0.903  (0.0088)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Hide Arm/Group Description NVA237 50 µg once daily (NVA237 + Tiotropium placebo + Flu/Sal). NVA237 50 μg o.d., delivered via single-dose dry-powder inhaler (SDDPI) o.d. plus Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Tiotropium 18µg once daily (NVA237 placebo + Tiotropium + Flu/Sal). Tiotropium 18 μg o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication. Placebo (NVA237 placebo + Tiotropium placebo + Flu/Sal). Placebo to tiotropium o.d. delivered via a proprietary inhalation device plus Placebo to NVA237 o.d. delivered via single-dose dry-powder inhaler (SDDPI) plus Flu/Sal 500/50 μg b.i.d. delivered via a proprietary inhalation device. In addition, at Visit 1, all participants were provided with a short acting β2-agonist (salbutamol) which they were instructed to use throughout the study as rescue medication.
All-Cause Mortality
NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/257 (5.84%)   22/258 (8.53%)   15/257 (5.84%) 
Blood and lymphatic system disorders       
Anaemia † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Cardiac disorders       
Acute coronary syndrome † 1  0/257 (0.00%)  1/258 (0.39%)  1/257 (0.39%) 
Angina pectoris † 1  0/257 (0.00%)  1/258 (0.39%)  1/257 (0.39%) 
Atrial fibrillation † 1  0/257 (0.00%)  2/258 (0.78%)  1/257 (0.39%) 
Atrial flutter † 1  1/257 (0.39%)  1/258 (0.39%)  0/257 (0.00%) 
Atrioventricular block complete † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Cardiac failure congestive † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Tachyarrhythmia † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Ventricular fibrillation † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Ear and labyrinth disorders       
Vertigo † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Gastrointestinal disorders       
Abdominal pain upper † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Duodenal ulcer † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Erosive oesophagitis † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Inguinal hernia strangulated † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Oral disorder † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Small intestinal obstruction † 1  2/257 (0.78%)  0/258 (0.00%)  0/257 (0.00%) 
General disorders       
Chest discomfort † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Chest pain † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Multi-organ failure † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Hepatobiliary disorders       
Ischaemic hepatitis † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Infections and infestations       
Breast abscess † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Cellulitis † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Herpes zoster † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Infective exacerbation of chronic obstructive airways disease † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Lobar pneumonia † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Pharyngitis † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Pneumonia † 1  0/257 (0.00%)  2/258 (0.78%)  2/257 (0.78%) 
Pneumonia viral † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Urosepsis † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Wound infection † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Injury, poisoning and procedural complications       
Accidental overdose † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Contusion † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Fall † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Femoral neck fracture † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Foreign body † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Post procedural haematoma † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Radius fracture † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Spinal compression fracture † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Investigations       
International normalised ratio increased † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Metabolism and nutrition disorders       
Dehydration † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Gout † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Musculoskeletal and connective tissue disorders       
Joint effusion † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Lumbar spinal stenosis † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Prostate cancer † 1  0/257 (0.00%)  1/258 (0.39%)  1/257 (0.39%) 
Nervous system disorders       
Subarachnoid haemorrhage † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis † 1  0/257 (0.00%)  0/258 (0.00%)  1/257 (0.39%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease † 1  0/257 (0.00%)  1/258 (0.39%)  2/257 (0.78%) 
Dyspnoea † 1  0/257 (0.00%)  1/258 (0.39%)  1/257 (0.39%) 
Lung disorder † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Pleural effusion † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Pleurisy † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Pulmonary embolism † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Pulmonary oedema † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Vascular disorders       
Deep vein thrombosis † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Femoral artery aneurysm † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Haematoma † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
Orthostatic hypotension † 1  1/257 (0.39%)  0/258 (0.00%)  0/257 (0.00%) 
Peripheral ischaemia † 1  0/257 (0.00%)  1/258 (0.39%)  0/257 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
NVA237 + Fluticasone/Salmeterol (Flu/Sal) Tiotropium + Flu/Sal Flu/Sal
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   114/257 (44.36%)   124/258 (48.06%)   111/257 (43.19%) 
Cardiac disorders       
Palpitations † 1  0/257 (0.00%)  3/258 (1.16%)  0/257 (0.00%) 
Eye disorders       
Conjunctivitis † 1  0/257 (0.00%)  3/258 (1.16%)  3/257 (1.17%) 
Gastrointestinal disorders       
Constipation † 1  4/257 (1.56%)  2/258 (0.78%)  2/257 (0.78%) 
Diarrhoea † 1  5/257 (1.95%)  2/258 (0.78%)  2/257 (0.78%) 
Dry mouth † 1  5/257 (1.95%)  9/258 (3.49%)  2/257 (0.78%) 
Gastrooesophageal reflux disease † 1  2/257 (0.78%)  3/258 (1.16%)  2/257 (0.78%) 
Mouth ulceration † 1  3/257 (1.17%)  0/258 (0.00%)  0/257 (0.00%) 
Nausea † 1  3/257 (1.17%)  9/258 (3.49%)  3/257 (1.17%) 
General disorders       
Chest discomfort † 1  2/257 (0.78%)  3/258 (1.16%)  0/257 (0.00%) 
Chest pain † 1  3/257 (1.17%)  2/258 (0.78%)  3/257 (1.17%) 
Fatigue † 1  0/257 (0.00%)  5/258 (1.94%)  2/257 (0.78%) 
Oedema peripheral † 1  3/257 (1.17%)  3/258 (1.16%)  1/257 (0.39%) 
Infections and infestations       
Bronchitis † 1  2/257 (0.78%)  1/258 (0.39%)  3/257 (1.17%) 
Diverticulitis † 1  0/257 (0.00%)  1/258 (0.39%)  3/257 (1.17%) 
Gastroenteritis † 1  1/257 (0.39%)  3/258 (1.16%)  2/257 (0.78%) 
Lower respiratory tract infection † 1  7/257 (2.72%)  5/258 (1.94%)  4/257 (1.56%) 
Nasopharyngitis † 1  3/257 (1.17%)  7/258 (2.71%)  5/257 (1.95%) 
Oral candidiasis † 1  12/257 (4.67%)  13/258 (5.04%)  9/257 (3.50%) 
Sinusitis † 1  2/257 (0.78%)  2/258 (0.78%)  5/257 (1.95%) 
Upper respiratory tract infection † 1  17/257 (6.61%)  13/258 (5.04%)  11/257 (4.28%) 
Viral upper respiratory tract infection † 1  3/257 (1.17%)  4/258 (1.55%)  5/257 (1.95%) 
Wound infection † 1  3/257 (1.17%)  1/258 (0.39%)  0/257 (0.00%) 
Injury, poisoning and procedural complications       
Fall † 1  3/257 (1.17%)  2/258 (0.78%)  3/257 (1.17%) 
Laceration † 1  2/257 (0.78%)  3/258 (1.16%)  2/257 (0.78%) 
Limb injury † 1  1/257 (0.39%)  3/258 (1.16%)  0/257 (0.00%) 
Muscle strain † 1  4/257 (1.56%)  3/258 (1.16%)  4/257 (1.56%) 
Investigations       
Weight increased † 1  3/257 (1.17%)  2/258 (0.78%)  1/257 (0.39%) 
Musculoskeletal and connective tissue disorders       
Back pain † 1  4/257 (1.56%)  8/258 (3.10%)  5/257 (1.95%) 
Muscle spasms † 1  11/257 (4.28%)  9/258 (3.49%)  5/257 (1.95%) 
Myalgia † 1  1/257 (0.39%)  4/258 (1.55%)  1/257 (0.39%) 
Osteoarthritis † 1  0/257 (0.00%)  2/258 (0.78%)  3/257 (1.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma † 1  3/257 (1.17%)  1/258 (0.39%)  2/257 (0.78%) 
Nervous system disorders       
Aphonia † 1  0/257 (0.00%)  3/258 (1.16%)  2/257 (0.78%) 
Dizziness † 1  2/257 (0.78%)  4/258 (1.55%)  4/257 (1.56%) 
Headache † 1  3/257 (1.17%)  4/258 (1.55%)  13/257 (5.06%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease † 1  0/257 (0.00%)  3/258 (1.16%)  4/257 (1.56%) 
Cough † 1  16/257 (6.23%)  15/258 (5.81%)  11/257 (4.28%) 
Dysphonia † 1  6/257 (2.33%)  15/258 (5.81%)  5/257 (1.95%) 
Dyspnoea † 1  7/257 (2.72%)  8/258 (3.10%)  9/257 (3.50%) 
Epistaxis † 1  4/257 (1.56%)  4/258 (1.55%)  1/257 (0.39%) 
Oropharyngeal pain † 1  9/257 (3.50%)  10/258 (3.88%)  8/257 (3.11%) 
Productive cough † 1  2/257 (0.78%)  3/258 (1.16%)  1/257 (0.39%) 
Rhinorrhoea † 1  6/257 (2.33%)  1/258 (0.39%)  3/257 (1.17%) 
Sputum increased † 1  3/257 (1.17%)  3/258 (1.16%)  2/257 (0.78%) 
Skin and subcutaneous tissue disorders       
Pruritus † 1  3/257 (1.17%)  0/258 (0.00%)  1/257 (0.39%) 
Vascular disorders       
Hypertension † 1  3/257 (1.17%)  6/258 (2.33%)  5/257 (1.95%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[Not Specified]
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01513460    
Other Study ID Numbers: CNVA237AAU01
First Submitted: January 16, 2012
First Posted: January 20, 2012
Results First Submitted: December 10, 2014
Results First Posted: January 5, 2015
Last Update Posted: January 5, 2015