Trial Outcomes & Findings for Efficacy, Tolerability and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease (NCT NCT01513460)
NCT ID: NCT01513460
Last Updated: 2015-01-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
773 participants
Primary outcome timeframe
baseline, 12 weeks
Results posted on
2015-01-05
Participant Flow
Participant milestones
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
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 + Flu/Sal
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.
|
Flu/Sal
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 Study
STARTED
|
258
|
258
|
257
|
|
Overall Study
Full Analysis Set
|
257
|
258
|
257
|
|
Overall Study
Per-protocol Set
|
196
|
186
|
166
|
|
Overall Study
COMPLETED
|
229
|
226
|
201
|
|
Overall Study
NOT COMPLETED
|
29
|
32
|
56
|
Reasons for withdrawal
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
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 + Flu/Sal
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.
|
Flu/Sal
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 Study
Death
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
2
|
|
Overall Study
Abnormal laboratory value
|
1
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
2
|
5
|
|
Overall Study
Protocol deviations
|
3
|
4
|
3
|
|
Overall Study
Withdrawal by Subject
|
7
|
8
|
21
|
|
Overall Study
Adverse Event
|
16
|
18
|
23
|
|
Overall Study
Abnormal test procedure
|
1
|
0
|
0
|
Baseline Characteristics
Efficacy, Tolerability and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease
Baseline characteristics by cohort
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=257 Participants
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 + Flu/Sal
n=258 Participants
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.
|
Flu/Sal
n=257 Participants
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
n=772 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
68.2 Years
STANDARD_DEVIATION 8.38 • n=5 Participants
|
68.0 Years
STANDARD_DEVIATION 7.74 • n=7 Participants
|
67.8 Years
STANDARD_DEVIATION 8.49 • n=5 Participants
|
68.0 Years
STANDARD_DEVIATION 8.20 • n=4 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
275 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
163 Participants
n=5 Participants
|
160 Participants
n=7 Participants
|
174 Participants
n=5 Participants
|
497 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: baseline, 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=194 Participants
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 + Flu/Sal
n=185 Participants
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.
|
Flu/Sal
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.
|
|---|---|---|---|
|
Change From Baseline in Mean Trough Forced Expiratory Volume in 1 Second (FEV1) (NVA237 Versus Tiotropium)
|
0.095 liters
Standard Error 0.0131
|
0.102 liters
Standard Error 0.0135
|
—
|
SECONDARY outcome
Timeframe: baseline, 4 weeks, 8 weeks, 12 weeksPopulation: Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=257 Participants
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 + Flu/Sal
n=515 Participants
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.
|
Flu/Sal
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.
|
|---|---|---|---|
|
Change From Baseline in Mean Trough FEV1 (Flu/Sal Versus NVA237/Tiotropium+Flu/Sal)
Week 12
|
-0.012 Liters
Standard Error 0.0099
|
0.088 Liters
Standard Error 0.0073
|
—
|
|
Change From Baseline in Mean Trough FEV1 (Flu/Sal Versus NVA237/Tiotropium+Flu/Sal)
Week 4
|
-0.010 Liters
Standard Error 0.0099
|
0.077 Liters
Standard Error 0.0073
|
—
|
|
Change From Baseline in Mean Trough FEV1 (Flu/Sal Versus NVA237/Tiotropium+Flu/Sal)
Week 8
|
-0.002 Liters
Standard Error 0.0099
|
0.088 Liters
Standard Error 0.0073
|
—
|
SECONDARY outcome
Timeframe: baseline, 4 weeks, 8 weeks, 12 weeksPopulation: Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=257 Participants
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 + Flu/Sal
n=258 Participants
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.
|
Flu/Sal
n=257 Participants
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.
|
|---|---|---|---|
|
Change From Baseline in Mean Trough FEV1
Week 4
|
0.077 Liters
Standard Error 0.0100
|
0.077 Liters
Standard Error 0.0101
|
-0.010 Liters
Standard Error 0.0099
|
|
Change From Baseline in Mean Trough FEV1
Week 8
|
0.084 Liters
Standard Error 0.0100
|
0.092 Liters
Standard Error 0.0101
|
-0.002 Liters
Standard Error 0.0099
|
|
Change From Baseline in Mean Trough FEV1
Week 12
|
0.089 Liters
Standard Error 0.0100
|
0.087 Liters
Standard Error 0.0101
|
-0.012 Liters
Standard Error 0.0099
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=257 Participants
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 + Flu/Sal
n=258 Participants
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.
|
Flu/Sal
n=257 Participants
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.
|
|---|---|---|---|
|
Change From Baseline in Total Score of the St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) After 12 Weeks of Treatment
|
-2.806 units on a scale
Standard Error 0.6772
|
-3.902 units on a scale
Standard Error 0.6920
|
-0.652 units on a scale
Standard Error 0.6871
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=247 Participants
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 + Flu/Sal
n=251 Participants
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.
|
Flu/Sal
n=241 Participants
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.
|
|---|---|---|---|
|
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Use
|
2.191 puffs of rescue medication
Standard Error 0.1384
|
2.093 puffs of rescue medication
Standard Error 0.1397
|
2.908 puffs of rescue medication
Standard Error 0.1395
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: 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.
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'.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=242 Participants
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 + Flu/Sal
n=251 Participants
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.
|
Flu/Sal
n=239 Participants
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.
|
|---|---|---|---|
|
Mean Percentage of Nights With 'no Nighttime Awakenings'
|
0.834 Percentage of nights
Standard Error 0.0124
|
0.816 Percentage of nights
Standard Error 0.0124
|
0.823 Percentage of nights
Standard Error 0.0124
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: 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.
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'.
Outcome measures
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=243 Participants
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 + Flu/Sal
n=248 Participants
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.
|
Flu/Sal
n=237 Participants
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.
|
|---|---|---|---|
|
Mean Percentage of Days With Performance of Usual Activities
|
0.934 Percentage of days
Standard Error 0.0087
|
0.946 Percentage of days
Standard Error 0.0088
|
0.903 Percentage of days
Standard Error 0.0088
|
Adverse Events
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
Serious events: 15 serious events
Other events: 114 other events
Deaths: 0 deaths
Tiotropium + Flu/Sal
Serious events: 22 serious events
Other events: 124 other events
Deaths: 0 deaths
Flu/Sal
Serious events: 15 serious events
Other events: 111 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=257 participants at risk
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 + Flu/Sal
n=258 participants at risk
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.
|
Flu/Sal
n=257 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/257
|
0.39%
1/258
|
0.39%
1/257
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/257
|
0.39%
1/258
|
0.39%
1/257
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/257
|
0.78%
2/258
|
0.39%
1/257
|
|
Cardiac disorders
Atrial flutter
|
0.39%
1/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Cardiac disorders
Atrioventricular block complete
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Cardiac disorders
Tachyarrhythmia
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Cardiac disorders
Ventricular fibrillation
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Ear and labyrinth disorders
Vertigo
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Erosive oesophagitis
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Inguinal hernia strangulated
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Oral disorder
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.78%
2/257
|
0.00%
0/258
|
0.00%
0/257
|
|
General disorders
Chest discomfort
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
General disorders
Chest pain
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
General disorders
Multi-organ failure
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Hepatobiliary disorders
Ischaemic hepatitis
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Infections and infestations
Breast abscess
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Infections and infestations
Cellulitis
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Infections and infestations
Pneumonia
|
0.00%
0/257
|
0.78%
2/258
|
0.78%
2/257
|
|
Infections and infestations
Pneumonia viral
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Infections and infestations
Urosepsis
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Infections and infestations
Wound infection
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Foreign body
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Investigations
International normalised ratio increased
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/257
|
0.39%
1/258
|
0.39%
1/257
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/257
|
0.39%
1/258
|
0.78%
2/257
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/257
|
0.39%
1/258
|
0.39%
1/257
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Vascular disorders
Femoral artery aneurysm
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Vascular disorders
Haematoma
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Vascular disorders
Orthostatic hypotension
|
0.39%
1/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/257
|
0.39%
1/258
|
0.00%
0/257
|
Other adverse events
| Measure |
NVA237 + Fluticasone/Salmeterol (Flu/Sal)
n=257 participants at risk
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 + Flu/Sal
n=258 participants at risk
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.
|
Flu/Sal
n=257 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.39%
1/257
|
1.2%
3/258
|
0.78%
2/257
|
|
Infections and infestations
Lower respiratory tract infection
|
2.7%
7/257
|
1.9%
5/258
|
1.6%
4/257
|
|
Cardiac disorders
Palpitations
|
0.00%
0/257
|
1.2%
3/258
|
0.00%
0/257
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/257
|
1.2%
3/258
|
1.2%
3/257
|
|
Gastrointestinal disorders
Constipation
|
1.6%
4/257
|
0.78%
2/258
|
0.78%
2/257
|
|
Gastrointestinal disorders
Diarrhoea
|
1.9%
5/257
|
0.78%
2/258
|
0.78%
2/257
|
|
Gastrointestinal disorders
Dry mouth
|
1.9%
5/257
|
3.5%
9/258
|
0.78%
2/257
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.78%
2/257
|
1.2%
3/258
|
0.78%
2/257
|
|
Gastrointestinal disorders
Mouth ulceration
|
1.2%
3/257
|
0.00%
0/258
|
0.00%
0/257
|
|
Gastrointestinal disorders
Nausea
|
1.2%
3/257
|
3.5%
9/258
|
1.2%
3/257
|
|
General disorders
Chest discomfort
|
0.78%
2/257
|
1.2%
3/258
|
0.00%
0/257
|
|
General disorders
Chest pain
|
1.2%
3/257
|
0.78%
2/258
|
1.2%
3/257
|
|
General disorders
Fatigue
|
0.00%
0/257
|
1.9%
5/258
|
0.78%
2/257
|
|
General disorders
Oedema peripheral
|
1.2%
3/257
|
1.2%
3/258
|
0.39%
1/257
|
|
Infections and infestations
Bronchitis
|
0.78%
2/257
|
0.39%
1/258
|
1.2%
3/257
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/257
|
0.39%
1/258
|
1.2%
3/257
|
|
Infections and infestations
Nasopharyngitis
|
1.2%
3/257
|
2.7%
7/258
|
1.9%
5/257
|
|
Infections and infestations
Oral candidiasis
|
4.7%
12/257
|
5.0%
13/258
|
3.5%
9/257
|
|
Infections and infestations
Sinusitis
|
0.78%
2/257
|
0.78%
2/258
|
1.9%
5/257
|
|
Infections and infestations
Upper respiratory tract infection
|
6.6%
17/257
|
5.0%
13/258
|
4.3%
11/257
|
|
Infections and infestations
Viral upper respiratory tract infection
|
1.2%
3/257
|
1.6%
4/258
|
1.9%
5/257
|
|
Infections and infestations
Wound infection
|
1.2%
3/257
|
0.39%
1/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Fall
|
1.2%
3/257
|
0.78%
2/258
|
1.2%
3/257
|
|
Injury, poisoning and procedural complications
Laceration
|
0.78%
2/257
|
1.2%
3/258
|
0.78%
2/257
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.39%
1/257
|
1.2%
3/258
|
0.00%
0/257
|
|
Injury, poisoning and procedural complications
Muscle strain
|
1.6%
4/257
|
1.2%
3/258
|
1.6%
4/257
|
|
Investigations
Weight increased
|
1.2%
3/257
|
0.78%
2/258
|
0.39%
1/257
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.6%
4/257
|
3.1%
8/258
|
1.9%
5/257
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
4.3%
11/257
|
3.5%
9/258
|
1.9%
5/257
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.39%
1/257
|
1.6%
4/258
|
0.39%
1/257
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/257
|
0.78%
2/258
|
1.2%
3/257
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.2%
3/257
|
0.39%
1/258
|
0.78%
2/257
|
|
Nervous system disorders
Aphonia
|
0.00%
0/257
|
1.2%
3/258
|
0.78%
2/257
|
|
Nervous system disorders
Dizziness
|
0.78%
2/257
|
1.6%
4/258
|
1.6%
4/257
|
|
Nervous system disorders
Headache
|
1.2%
3/257
|
1.6%
4/258
|
5.1%
13/257
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/257
|
1.2%
3/258
|
1.6%
4/257
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
16/257
|
5.8%
15/258
|
4.3%
11/257
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
2.3%
6/257
|
5.8%
15/258
|
1.9%
5/257
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.7%
7/257
|
3.1%
8/258
|
3.5%
9/257
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.6%
4/257
|
1.6%
4/258
|
0.39%
1/257
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
3.5%
9/257
|
3.9%
10/258
|
3.1%
8/257
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.78%
2/257
|
1.2%
3/258
|
0.39%
1/257
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
2.3%
6/257
|
0.39%
1/258
|
1.2%
3/257
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
1.2%
3/257
|
1.2%
3/258
|
0.78%
2/257
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.2%
3/257
|
0.00%
0/258
|
0.39%
1/257
|
|
Vascular disorders
Hypertension
|
1.2%
3/257
|
2.3%
6/258
|
1.9%
5/257
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER