Trial Outcomes & Findings for A 12 Week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation. (NCT NCT01727141)
NCT ID: NCT01727141
Last Updated: 2016-03-29
Results Overview
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction. Missing values of FEV1 AUC0-12 at Day 1 and Week 12 will not imputed. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.
COMPLETED
PHASE3
1042 participants
baseline (BL), 12 Weeks
2016-03-29
Participant Flow
Participants were randomized to each treatment arm in a 1:1:1:1 ratio.
One thousand forty two participants were randomized. (One participant was randomized twice and was counted twice in the randomized set.) In the safety set, participants were analyzed according to the treatment received.
Participant milestones
| Measure |
QVA149
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
27.5 ug b.i.d.
|
NVA237
12.5 ug b.i.d.
|
Placebo
b.i.d
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
260
|
260
|
261
|
261
|
|
Overall Study
Safety Set
|
258
|
260
|
262
|
260
|
|
Overall Study
Full Analysis Set
|
258
|
260
|
261
|
261
|
|
Overall Study
COMPLETED
|
255
|
251
|
258
|
246
|
|
Overall Study
NOT COMPLETED
|
5
|
9
|
3
|
15
|
Reasons for withdrawal
| Measure |
QVA149
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
27.5 ug b.i.d.
|
NVA237
12.5 ug b.i.d.
|
Placebo
b.i.d
|
|---|---|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
0
|
0
|
|
Overall Study
Death
|
0
|
1
|
1
|
1
|
|
Overall Study
Protocol deviation
|
1
|
1
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
2
|
11
|
Baseline Characteristics
A 12 Week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation.
Baseline characteristics by cohort
| Measure |
QVA149
n=260 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 Participants
27.5 ug b.i.d.
|
NVA237
n=261 Participants
12.5 ug b.i.d.
|
Placebo
n=261 Participants
b.i.d
|
Total
n=1042 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
63.9 Years
STANDARD_DEVIATION 8.76 • n=5 Participants
|
63.7 Years
STANDARD_DEVIATION 8.07 • n=7 Participants
|
63.7 Years
STANDARD_DEVIATION 8.35 • n=5 Participants
|
63.7 Years
STANDARD_DEVIATION 8.19 • n=4 Participants
|
63.8 Years
STANDARD_DEVIATION 8.33 • n=21 Participants
|
|
Sex: Female, Male
Female
|
90 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
92 Participants
n=4 Participants
|
334 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
170 Participants
n=5 Participants
|
186 Participants
n=7 Participants
|
183 Participants
n=5 Participants
|
169 Participants
n=4 Participants
|
708 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: baseline (BL), 12 WeeksPopulation: Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study treatment. Participants, who were missing day 1 and/or week 12 FEV1 AUC 0-12h measurements, were not included in the analysis.
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction. Missing values of FEV1 AUC0-12 at Day 1 and Week 12 will not imputed. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.
Outcome measures
| Measure |
QVA149
n=258 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 Participants
27.5 ug b.i.d.
|
NVA237
n=261 Participants
12.5 ug b.i.d.
|
Placebo
n=260 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))
|
0.211 Liter
Standard Error 0.0140
|
0.117 Liter
Standard Error 0.0140
|
0.112 Liter
Standard Error 0.0141
|
-0.021 Liter
Standard Error 0.0145
|
SECONDARY outcome
Timeframe: BL, 12 WeeksPopulation: Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study treatment. Participants missing week 12 data were not included in the analysis.
Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. Missing week 12 data were imputed with Last Observation Carried Forward (LOCF) method but only if measured at day \>= 29. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
QVA149
n=246 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=244 Participants
27.5 ug b.i.d.
|
NVA237
n=243 Participants
12.5 ug b.i.d.
|
Placebo
n=223 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
|
-6.4 score on a scale
Standard Error 0.75
|
-4.6 score on a scale
Standard Error 0.75
|
-4.8 score on a scale
Standard Error 0.75
|
-2.7 score on a scale
Standard Error 0.78
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants from the full analysis set, who had a SGRQ total score, were included in the analysis. The full analysis set included all randomized participants who received at least one dose of study treatment.
Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
Outcome measures
| Measure |
QVA149
n=246 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=244 Participants
27.5 ug b.i.d.
|
NVA237
n=243 Participants
12.5 ug b.i.d.
|
Placebo
n=223 Participants
b.i.d
|
|---|---|---|---|---|
|
Percentage of Participants With a Clinically Important Improvement of at Least 4 Units in the SGRQ Total Score
|
57.3 Percentage of participants
|
48.0 Percentage of participants
|
46.1 Percentage of participants
|
39.0 Percentage of participants
|
SECONDARY outcome
Timeframe: BL, day 2, day 86Population: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Pulmonary function assessments were performed using centralized spirometry according to international standards. Trough FEV1 was analyzed using the same MMRM as specified for FEV1. Trough FEV1 was defined as the mean of FEV1 at 23 h 15 min and 23 h 45 min after the morning dose of the previous day. Before the mean was calculated, a time window of 10 - 13 hours post-evening dose was applied to these 2 measurements. Recordings outside the time window were set to missing.
Outcome measures
| Measure |
QVA149
n=256 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=257 Participants
27.5 ug b.i.d.
|
NVA237
n=260 Participants
12.5 ug b.i.d.
|
Placebo
n=252 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in Trough FEV1
day 2
|
0.187 Liters
Standard Error 0.0102
|
0.109 Liters
Standard Error 0.0102
|
0.112 Liters
Standard Error 0.0101
|
0.015 Liters
Standard Error 0.0103
|
|
Change From Baseline in Trough FEV1
day 86
|
0.201 Liters
Standard Error 0.0144
|
0.120 Liters
Standard Error 0.0142
|
0.092 Liters
Standard Error 0.0142
|
-0.012 Liters
Standard Error 0.0150
|
SECONDARY outcome
Timeframe: BL, day 85Population: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 values, were included in the analysis.
Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was analyzed using the same MMRM as specified for FEV1. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose. Since the time of evening dose of the previous day was not recorded at these visits, no time window was applied.
Outcome measures
| Measure |
QVA149
n=254 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=254 Participants
27.5 ug b.i.d.
|
NVA237
n=257 Participants
12.5 ug b.i.d.
|
Placebo
n=244 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in Pre-dose Trough FEV1
|
0.161 Liters
Standard Error 0.0140
|
0.083 Liters
Standard Error 0.0140
|
0.061 Liters
Standard Error 0.0140
|
-0.035 Liters
Standard Error 0.0145
|
SECONDARY outcome
Timeframe: BL, Day 1:5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min;Day 2: 23h15min, 23h45min;Day 15: -45min, -15min, 1h;Day 29: -45 min, -15min, 1h;Day 57: -45min, -15min, 1h;Day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55min;Day 86: 23h15min; 23h45minPopulation: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study medication. Participants, who has both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction.
Outcome measures
| Measure |
QVA149
n=258 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 Participants
27.5 ug b.i.d.
|
NVA237
n=261 Participants
12.5 ug b.i.d.
|
Placebo
n=261 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in FEV1
Day 1, 2 h (n=254,257,261,254)
|
0.219 Liters
Standard Error 0.0091
|
0.104 Liters
Standard Error 0.0091
|
0.179 Liters
Standard Error 0.0089
|
0.037 Liters
Standard Error 0.0090
|
|
Change From Baseline in FEV1
Day 1, 4 h (n=252,260,256,254)
|
0.207 Liters
Standard Error 0.0103
|
0.105 Liters
Standard Error 0.0103
|
0.146 Liters
Standard Error 0.0101
|
0.039 Liters
Standard Error 0.0103
|
|
Change From Baseline in FEV1
Day 1, 6 h (n=253,256,254,248)
|
0.178 Liters
Standard Error 0.0105
|
0.102 Liters
Standard Error 0.0105
|
0.125 Liters
Standard Error 0.0104
|
0.021 Liters
Standard Error 0.0107
|
|
Change From Baseline in FEV1
Day 1, 8 h (n=253,251,256,248)
|
0.157 Liters
Standard Error 0.0100
|
0.081 Liters
Standard Error 0.0102
|
0.106 Liters
Standard Error 0.0101
|
0.004 Liters
Standard Error 0.0104
|
|
Change From Baseline in FEV1
Day 1, 11 h (n=246,250,253,245)
|
0.116 Liters
Standard Error 0.0112
|
0.047 Liters
Standard Error 0.0112
|
0.073 Liters
Standard Error 0.0111
|
-0.020 Liters
Standard Error 0.0113
|
|
Change From Baseline in FEV1
Day 2, 23h 15 min (n=249,249,254,242)
|
0.176 Liters
Standard Error 0.0106
|
0.104 Liters
Standard Error 0.0106
|
0.106 Liters
Standard Error 0.0104
|
0.004 Liters
Standard Error 0.0107
|
|
Change From Baseline in FEV1
Day 29, -15 min (n=254,254,256,243)
|
0.193 Liters
Standard Error 0.0128
|
0.131 Liters
Standard Error 0.0127
|
0.092 Liters
Standard Error 0.0127
|
-0.006 Liters
Standard Error 0.0130
|
|
Change From Baseline in FEV1
Day 1, 5 min (n=255,257,260,255)
|
0.111 Liters
Standard Error 0.0062
|
0.071 Liters
Standard Error 0.0062
|
0.065 Liters
Standard Error 0.0062
|
0.009 Liters
Standard Error 0.0062
|
|
Change From Baseline in FEV1
Day 1, 15 min (n=256,256,261,258)
|
0.146 Liters
Standard Error 0.0070
|
0.088 Liters
Standard Error 0.0070
|
0.117 Liters
Standard Error 0.0069
|
0.012 Liters
Standard Error 0.0070
|
|
Change From Baseline in FEV1
Day 1, 1 h (n=258,260,261,258)
|
0.179 Liters
Standard Error 0.0082
|
0.085 Liters
Standard Error 0.0082
|
0.166 Liters
Standard Error 0.0081
|
0.016 Liters
Standard Error 0.0082
|
|
Change From Baseline in FEV1
Day 2, 23h 45min (n= 255,254,258,250)
|
0.194 Liters
Standard Error 0.0108
|
0.119 Liters
Standard Error 0.0109
|
0.119 Liters
Standard Error 0.0107
|
0.022 Liters
Standard Error 0.0110
|
|
Change From Baseline in FEV1
Day 15, -45min (n=254,254,256,244)
|
0.168 Liters
Standard Error 0.0123
|
0.114 Liters
Standard Error 0.0124
|
0.067 Liters
Standard Error 0.0122
|
-0.023 Liters
Standard Error 0.0126
|
|
Change From Baseline in FEV1
Day 15, -15 min (n=254,254,256,243)
|
0.185 Liters
Standard Error 0.0125
|
0.139 Liters
Standard Error 0.0126
|
0.087 Liters
Standard Error 0.0125
|
-0.008 Liters
Standard Error 0.0129
|
|
Change From Baseline in FEV1
Day 15, 1 h (n=258,260,261,258)
|
0.269 Liters
Standard Error 0.0133
|
0.173 Liters
Standard Error 0.0134
|
0.161 Liters
Standard Error 0.0133
|
0.004 Liters
Standard Error 0.0136
|
|
Change From Baseline in FEV1
Day 29, -45 min (n=254,254,256,244)
|
0.175 Liters
Standard Error 0.0123
|
0.111 Liters
Standard Error 0.0124
|
0.073 Liters
Standard Error 0.0123
|
-0.029 Liters
Standard Error 0.0126
|
|
Change From Baseline in FEV1
Day 29, 1 h (n=258,260, 261,258)
|
0.271 Liters
Standard Error 0.0135
|
0.167 Liters
Standard Error 0.0135
|
0.156 Liters
Standard Error 0.0135
|
0.006 Liters
Standard Error 0.0138
|
|
Change From Baseline in FEV1
Day 57, -45 min (n=254,254,256,244)
|
0.181 Liters
Standard Error 0.0134
|
0.097 Liters
Standard Error 0.0134
|
0.069 Liters
Standard Error 0.0133
|
-0.016 Liters
Standard Error 0.0137
|
|
Change From Baseline in FEV1
Day 57, -15 min (n=254,254,256,243)
|
0.193 Liters
Standard Error 0.0132
|
0.117 Liters
Standard Error 0.0132
|
0.094 Liters
Standard Error 0.0132
|
0.006 Liters
Standard Error 0.0136
|
|
Change From Baseline in FEV1
Day 57, 1 h (n=258,260,261,258)
|
0.273 Liters
Standard Error 0.0141
|
0.150 Liters
Standard Error 0.0141
|
0.161 Liters
Standard Error 0.0140
|
0.008 Liters
Standard Error 0.0144
|
|
Change From Baseline in FEV1
Day 85, -45 min (n= 254,254,256,244)
|
0.154 Liters
Standard Error 0.0142
|
0.080 Liters
Standard Error 0.0142
|
0.051 Liters
Standard Error 0.0142
|
-0.038 Liters
Standard Error 0.0146
|
|
Change From Baseline in FEV1
Day 85, -15 min (n=254,254,256,243)
|
0.171 Liters
Standard Error 0.0144
|
0.088 Liters
Standard Error 0.0144
|
0.073 Liters
Standard Error 0.0143
|
-0.035 Liters
Standard Error 0.0149
|
|
Change From Baseline in FEV1
Day 85, 5 min (n=255,257,260,255)
|
0.232 Liters
Standard Error 0.0147
|
0.119 Liters
Standard Error 0.0148
|
0.106 Liters
Standard Error 0.0149
|
-0.036 Liters
Standard Error 0.0154
|
|
Change From Baseline in FEV1
Day 85, 15 min (n=256,256,261,258)
|
0.242 Liters
Standard Error 0.0150
|
0.143 Liters
Standard Error 0.0151
|
0.130 Liters
Standard Error 0.0152
|
-0.020 Liters
Standard Error 0.0159
|
|
Change From Baseline in FEV1
Day 85, 1 h (n=258,260,261,258)
|
0.250 Liters
Standard Error 0.0149
|
0.136 Liters
Standard Error 0.0149
|
0.150 Liters
Standard Error 0.0150
|
-0.021 Liters
Standard Error 0.0154
|
|
Change From Baseline in FEV1
Day 85, 2 h 9n=254,257,261,254)
|
0.265 Liters
Standard Error 0.0150
|
0.145 Liters
Standard Error 0.0150
|
0.171 Liters
Standard Error 0.0151
|
-0.009 Liters
Standard Error 0.0157
|
|
Change From Baseline in FEV1
Day 85, 4 h (n=252,260,256,254)
|
0.242 Liters
Standard Error 0.0158
|
0.140 Liters
Standard Error 0.0155
|
0.132 Liters
Standard Error 0.0158
|
-0.001 Liters
Standard Error 0.0165
|
|
Change From Baseline in FEV1
Day 85, 6 h (n=253,256,254,248)
|
0.197 Liters
Standard Error 0.0154
|
0.123 Liters
Standard Error 0.0155
|
0.109 Liters
Standard Error 0.0157
|
-0.017 Liters
Standard Error 0.0162
|
|
Change From Baseline in FEV1
Day 85, 8 h (n=253,251,256,248)
|
0.180 Liters
Standard Error 0.0152
|
0.103 Liters
Standard Error 0.0152
|
0.086 Liters
Standard Error 0.0151
|
-0.030 Liters
Standard Error 0.0158
|
|
Change From Baseline in FEV1
Day 85, 11 h 55min(n=246,250,253,245)
|
0.143 Liters
Standard Error 0.0155
|
0.066 Liters
Standard Error 0.0154
|
0.055 Liters
Standard Error 0.0150
|
-0.064 Liters
Standard Error 0.0161
|
|
Change From Baseline in FEV1
Day 86, 23 h 15 min (n=249,249,254,242)
|
0.196 Liters
Standard Error 0.0149
|
0.116 Liters
Standard Error 0.0151
|
0.082 Liters
Standard Error 0.0151
|
-0.017 Liters
Standard Error 0.0155
|
|
Change From Baseline in FEV1
Day 86, 23 h 45 min (n=255,254,258,250)
|
0.216 Liters
Standard Error 0.0144
|
0.128 Liters
Standard Error 0.0144
|
0.100 Liters
Standard Error 0.0143
|
-0.004 Liters
Standard Error 0.0150
|
SECONDARY outcome
Timeframe: BL, Day 1: 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min;Day 2: 23h15min, 23h45min;Day 15: -45min, -15min, 1h;Day 29: -45 min, -15min, 1h;Day 57: -45min, -15min, 1h;Day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h 55min;Day 86: 23h15min; 23h45minPopulation: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study medication. Participants, who has both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FVC measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction.
Outcome measures
| Measure |
QVA149
n=258 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 Participants
27.5 ug b.i.d.
|
NVA237
n=261 Participants
12.5 ug b.i.d.
|
Placebo
n=261 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in FVC
Day 57, 1 h (n=258,260,261,258)
|
0.411 Liters
Standard Error 0.0241
|
0.239 Liters
Standard Error 0.0241
|
0.265 Liters
Standard Error 0.0240
|
0.030 Liters
Standard Error 0.0246
|
|
Change From Baseline in FVC
Day 85, -45 min (n=254,254,256,244)
|
0.247 Liters
Standard Error 0.0245
|
0.106 Liters
Standard Error 0.0245
|
0.092 Liters
Standard Error 0.0245
|
-0.055 Liters
Standard Error 0.0252
|
|
Change From Baseline in FVC
Day 85, 6 h (n=253,256,254,248)
|
0.290 Liters
Standard Error 0.0263
|
0.164 Liters
Standard Error 0.0265
|
0.176 Liters
Standard Error 0.0268
|
-0.033 Liters
Standard Error 0.0276
|
|
Change From Baseline in FVC
Day 1, 5 min (n=255,257,260,255)
|
0.234 Liters
Standard Error 0.0131
|
0.175 Liters
Standard Error 0.0132
|
0.136 Liters
Standard Error 0.0131
|
0.009 Liters
Standard Error 0.0131
|
|
Change From Baseline in FVC
Day 1, 15 min (n=256,256,261,258)
|
0.283 Liters
Standard Error 0.0146
|
0.200 Liters
Standard Error 0.0146
|
0.243 Liters
Standard Error 0.0145
|
0.032 Liters
Standard Error 0.0146
|
|
Change From Baseline in FVC
Day 1, 1 h (n=258,260,261,258)
|
0.329 Liters
Standard Error 0.0165
|
0.191 Liters
Standard Error 0.0164
|
0.292 Liters
Standard Error 0.0163
|
0.029 Liters
Standard Error 0.0164
|
|
Change From Baseline in FVC
Day 1, 2 h (n=254,257,261,254)
|
0.390 Liters
Standard Error 0.0180
|
0.220 Liters
Standard Error 0.0180
|
0.306 Liters
Standard Error 0.0177
|
0.076 Liters
Standard Error 0.0178
|
|
Change From Baseline in FVC
Day 1, 4 h (n=252,260,256,254)
|
0.355 Liters
Standard Error 0.0192
|
0.209 Liters
Standard Error 0.0192
|
0.253 Liters
Standard Error 0.0190
|
0.072 Liters
Standard Error 0.0192
|
|
Change From Baseline in FVC
Day 1, 6 h (n=253,256,254,248)
|
0.319 Liters
Standard Error 0.0198
|
0.214 Liters
Standard Error 0.0198
|
0.230 Liters
Standard Error 0.0197
|
0.043 Liters
Standard Error 0.0202
|
|
Change From Baseline in FVC
Day 1, 8 h (n=253,251,256,248)
|
0.306 Liters
Standard Error 0.0189
|
0.188 Liters
Standard Error 0.0192
|
0.195 Liters
Standard Error 0.0189
|
0.040 Liters
Standard Error 0.0195
|
|
Change From Baseline in FVC
Day 1, 11 h 55 min(n=246,250,253,245)
|
0.240 Liters
Standard Error 0.0208
|
0.122 Liters
Standard Error 0.0208
|
0.140 Liters
Standard Error 0.0207
|
-0.019 Liters
Standard Error 0.0210
|
|
Change From Baseline in FVC
Day 2, 23 h 15 min (n=249,249,254,242)
|
0.315 Liters
Standard Error 0.0194
|
0.214 Liters
Standard Error 0.0193
|
0.190 Liters
Standard Error 0.0190
|
0.013 Liters
Standard Error 0.0196
|
|
Change From Baseline in FVC
Day 2, 23 h 45 min (n=255,254,258,250)
|
0.337 Liters
Standard Error 0.0200
|
0.232 Liters
Standard Error 0.0203
|
0.201 Liters
Standard Error 0.0198
|
0.056 Liters
Standard Error 0.0230
|
|
Change From Baseline in FVC
Day 15, -45 min (n=254,254,256,244)
|
0.265 Liters
Standard Error 0.0227
|
0.188 Liters
Standard Error 0.0229
|
0.134 Liters
Standard Error 0.0225
|
-0.016 Liters
Standard Error 0.0232
|
|
Change From Baseline in FVC
Day 15, -15 min (n=254,254,256,243)
|
0.307 Liters
Standard Error 0.0234
|
0.206 Liters
Standard Error 0.0236
|
0.167 Liters
Standard Error 0.0233
|
0.032 Liters
Standard Error 0.0241
|
|
Change From Baseline in FVC
Day 15, 1 h (n=258,260,261,258)
|
0.419 Liters
Standard Error 0.0241
|
0.274 Liters
Standard Error 0.0242
|
0.269 Liters
Standard Error 0.0241
|
0.034 Liters
Standard Error 0.0246
|
|
Change From Baseline in FVC
Day 29, -45 min (n=254,254,256,244)
|
0.276 Liters
Standard Error 0.0225
|
0.177 Liters
Standard Error 0.0226
|
0.142 Liters
Standard Error 0.0224
|
-0.022 Liters
Standard Error 0.0231
|
|
Change From Baseline in FVC
Day 29, -15 min (n=254,254,256,243)
|
0.304 Liters
Standard Error 0.0228
|
0.203 Liters
Standard Error 0.0228
|
0.168 Liters
Standard Error 0.0227
|
0.017 Liters
Standard Error 0.0233
|
|
Change From Baseline in FVC
Day 29, 1 h (n=258,260,261,258)
|
0.422 Liters
Standard Error 0.0243
|
0.259 Liters
Standard Error 0.0244
|
0.272 Liters
Standard Error 0.0243
|
0.046 Liters
Standard Error 0.0248
|
|
Change From Baseline in FVC
Day 57, -45 min (n=254,254,256,244)
|
0.286 Liters
Standard Error 0.0235
|
0.153 Liters
Standard Error 0.0236
|
0.124 Liters
Standard Error 0.0234
|
-0.026 Liters
Standard Error 0.0240
|
|
Change From Baseline in FVC
Day 57, -15 min (n=254,254,256,243)
|
0.299 Liters
Standard Error 0.0234
|
0.177 Liters
Standard Error 0.0234
|
0.172 Liters
Standard Error 0.0234
|
0.022 Liters
Standard Error 0.0241
|
|
Change From Baseline in FVC
Day 85, -15 min (n=254,254,256,243)
|
0.264 Liters
Standard Error 0.0246
|
0.129 Liters
Standard Error 0.0247
|
0.134 Liters
Standard Error 0.0245
|
-0.058 Liters
Standard Error 0.0255
|
|
Change From Baseline in FVC
Day 85, 5 min (n=255,257,260,255)
|
0.350 Liters
Standard Error 0.0253
|
0.192 Liters
Standard Error 0.0255
|
0.179 Liters
Standard Error 0.0255
|
-0.031 Liters
Standard Error 0.0265
|
|
Change From Baseline in FVC
Day 85, 15 min (n=256,256,261,258)
|
0.378 Liters
Standard Error 0.0250
|
0.226 Liters
Standard Error 0.0252
|
0.226 Liters
Standard Error 0.0252
|
-0.011 Liters
Standard Error 0.0263
|
|
Change From Baseline in FVC
Day 85, 1 h (n=258,260,261,258)
|
0.366 Liters
Standard Error 0.0250
|
0.200 Liters
Standard Error 0.0250
|
0.243 Liters
Standard Error 0.0251
|
-0.024 Liters
Standard Error 0.0257
|
|
Change From Baseline in FVC
Day 85, 2 h (n=254,257,261,254)
|
0.380 Liters
Standard Error 0.0255
|
0.222 Liters
Standard Error 0.0255
|
0.285 Liters
Standard Error 0.0255
|
0.012 Liters
Standard Error 0.0265
|
|
Change From Baseline in FVC
Day 85, 4 h (n=252,260,256,254)
|
0.326 Liters
Standard Error 0.0260
|
0.201 Liters
Standard Error 0.0255
|
0.203 Liters
Standard Error 0.0259
|
0.008 Liters
Standard Error 0.0270
|
|
Change From Baseline in FVC
Day 85, 8h (n=253,251,256,248)
|
0.263 Liters
Standard Error 0.0259
|
0.154 Liters
Standard Error 0.0259
|
0.155 Liters
Standard Error 0.0258
|
-0.035 Liters
Standard Error 0.0269
|
|
Change From Baseline in FVC
Day 85, 11 55 min (n=246,250,253,245)
|
0.209 Liters
Standard Error 0.0261
|
0.109 Liters
Standard Error 0.0259
|
0.110 Liters
Standard Error 0.0253
|
-0.071 Liters
Standard Error 0.0271
|
|
Change From Baseline in FVC
Day 86, 23 h 15 min (n=249,249,254,242)
|
0.295 Liters
Standard Error 0.0250
|
0.160 Liters
Standard Error 0.0254
|
0.142 Liters
Standard Error 0.0253
|
-0.007 Liters
Standard Error 0.0259
|
|
Change From Baseline in FVC
Day 86, 23 h 45 min (n=255,254,258,250)
|
0.315 Liters
Standard Error 0.0243
|
0.186 Liters
Standard Error 0.0242
|
0.167 Liters
Standard Error 0.0240
|
0.029 Liters
Standard Error 0.0251
|
SECONDARY outcome
Timeframe: BL, day 1, week 12Population: Full Analysis Set: The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.
Outcome measures
| Measure |
QVA149
n=258 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 Participants
27.5 ug b.i.d.
|
NVA237
n=261 Participants
12.5 ug b.i.d.
|
Placebo
n=261 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
day 1, FEV1 AUC 0-4h (n=249,251,250,246)
|
0.194 Liters
Standard Error 0.0077
|
0.096 Liters
Standard Error 0.0077
|
0.158 Liters
Standard Error 0.0077
|
0.028 Liters
Standard Error 0.0077
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
day 1, FEV1 AUC 4-8h (n=257,260,261,257)
|
0.178 Liters
Standard Error 0.0093
|
0.096 Liters
Standard Error 0.0093
|
0.125 Liters
Standard Error 0.0093
|
0.023 Liters
Standard Error 0.0093
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
day 1, FEV1 AUC 0-12h (n=249,251,250,246)
|
0.171 Liters
Standard Error 0.0083
|
0.083 Liters
Standard Error 0.0083
|
0.128 Liters
Standard Error 0.0082
|
0.016 Liters
Standard Error 0.0083
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
week 12, FEV1 AUC 0-4h (n=249,251,250,246)
|
0.254 Liters
Standard Error 0.0144
|
0.141 Liters
Standard Error 0.0144
|
0.149 Liters
Standard Error 0.0145
|
-0.010 Liters
Standard Error 0.0150
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
week 12, FEV1 AUC 4-8h (n=257,260,261,257)
|
0.205 Liters
Standard Error 0.0145
|
0.121 Liters
Standard Error 0.0144
|
0.111 Liters
Standard Error 0.0145
|
-0.016 Liters
Standard Error 0.0151
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
day 1, FEV1 AUC 8-12h (n=254,256,259,253)
|
0.138 Liters
Standard Error 0.0097
|
0.065 Liters
Standard Error 0.0098
|
0.094 Liters
Standard Error 0.0097
|
-0.006 Liters
Standard Error 0.0098
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
week 12, FEV1 AUC 8-12h (n=254,256,259,253)
|
0.164 Liters
Standard Error 0.0145
|
0.084 Liters
Standard Error 0.0144
|
0.072 Liters
Standard Error 0.0143
|
-0.043 Liters
Standard Error 0.0151
|
|
Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
week 12, FEV1 AUC 0-12h (n=249,251,250,246)
|
0.211 Liters
Standard Error 0.0140
|
0.117 Liters
Standard Error 0.0140
|
0.112 Liters
Standard Error 0.0141
|
-0.021 Liters
Standard Error 0.0145
|
SECONDARY outcome
Timeframe: BL, 12 weeksPopulation: Full Analysis Set (FAS) The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 scores, were included in the analysis.
The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline.
Outcome measures
| Measure |
QVA149
n=246 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=240 Participants
27.5 ug b.i.d.
|
NVA237
n=246 Participants
12.5 ug b.i.d.
|
Placebo
n=226 Participants
b.i.d
|
|---|---|---|---|---|
|
Transitional Dyspnea Index (TDI) Focal Score
|
1.94 score on a scale
Standard Error 0.211
|
1.30 score on a scale
Standard Error 0.212
|
1.48 score on a scale
Standard Error 0.210
|
0.71 score on a scale
Standard Error 0.217
|
SECONDARY outcome
Timeframe: BL, 12 WeeksPopulation: Full Analysis Set (FAS) The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 values, were included in the analysis.
Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
QVA149
n=251 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=250 Participants
27.5 ug b.i.d.
|
NVA237
n=252 Participants
12.5 ug b.i.d.
|
Placebo
n=240 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
|
-2.22 Number of puffs
Standard Error 0.135
|
-1.72 Number of puffs
Standard Error 0.135
|
-1.65 Number of puffs
Standard Error 0.135
|
-1.00 Number of puffs
Standard Error 0.137
|
SECONDARY outcome
Timeframe: BL, 12 WeeksPopulation: Full Analysis Set (FAS) The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 values, were included in the analysis.
The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.
Outcome measures
| Measure |
QVA149
n=258 Participants
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 Participants
27.5 ug b.i.d.
|
NVA237
n=261 Participants
12.5 ug b.i.d.
|
Placebo
n=261 Participants
b.i.d
|
|---|---|---|---|---|
|
Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
Daily (n=251,250,252,240)
|
-1.30 score on a scale
Standard Error 0.104
|
-0.97 score on a scale
Standard Error 0.104
|
-0.99 score on a scale
Standard Error 0.104
|
-0.52 score on a scale
Standard Error 0.106
|
|
Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
Nighttime (n=244,248,248,234)
|
-1.07 score on a scale
Standard Error 0.106
|
-0.83 score on a scale
Standard Error 0.105
|
-0.85 score on a scale
Standard Error 0.105
|
-0.40 score on a scale
Standard Error 0.107
|
|
Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
Daytime (n=245,246,245,238)
|
-1.17 score on a scale
Standard Error 0.102
|
-0.85 score on a scale
Standard Error 0.102
|
-0.88 score on a scale
Standard Error 0.102
|
-0.38 score on a scale
Standard Error 0.103
|
Adverse Events
QVA149
QAB149
NVA237
Placebo
Serious adverse events
| Measure |
QVA149
n=258 participants at risk
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 participants at risk
27.5 ug b.i.d.
|
NVA237
n=262 participants at risk
12.5 ug b.i.d.
|
Placebo
n=260 participants at risk
b.i.d
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
NORMOCHROMIC NORMOCYTIC ANAEMIA
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
0.00%
0/260
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.78%
2/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Cardiac disorders
CARDIAC ARREST
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Gastrointestinal disorders
COLITIS
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Gastrointestinal disorders
SMALL INTESTINAL OBSTRUCTION
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.38%
1/260
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Hepatobiliary disorders
BILIARY COLIC
|
0.00%
0/258
|
0.00%
0/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Immune system disorders
ANAPHYLACTIC REACTION
|
0.00%
0/258
|
0.00%
0/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Infections and infestations
INFLUENZA
|
0.00%
0/258
|
0.00%
0/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/258
|
0.00%
0/260
|
0.76%
2/262
|
0.38%
1/260
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
0.39%
1/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Injury, poisoning and procedural complications
ALCOHOL POISONING
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
0.00%
0/260
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
0.00%
0/260
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER TRANSITIONAL CELL CARCINOMA
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SMALL CELL LUNG CANCER
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Nervous system disorders
BRAIN INJURY
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
0.00%
0/260
|
|
Nervous system disorders
LACUNAR INFARCTION
|
0.39%
1/258
|
0.00%
0/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Nervous system disorders
MIGRAINE
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
0.00%
0/260
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
0.00%
0/260
|
|
Respiratory, thoracic and mediastinal disorders
ASPIRATION
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.78%
2/258
|
1.9%
5/260
|
1.5%
4/262
|
1.2%
3/260
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/258
|
0.00%
0/260
|
0.00%
0/262
|
0.38%
1/260
|
|
Vascular disorders
PERIPHERAL ISCHAEMIA
|
0.00%
0/258
|
0.38%
1/260
|
0.00%
0/262
|
0.00%
0/260
|
Other adverse events
| Measure |
QVA149
n=258 participants at risk
27.5/12.5 ug twice daily (b.i.d) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=260 participants at risk
27.5 ug b.i.d.
|
NVA237
n=262 participants at risk
12.5 ug b.i.d.
|
Placebo
n=260 participants at risk
b.i.d
|
|---|---|---|---|---|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
1.5%
4/260
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.39%
1/258
|
0.77%
2/260
|
0.38%
1/262
|
1.5%
4/260
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
0.39%
1/258
|
0.00%
0/260
|
1.1%
3/262
|
0.00%
0/260
|
|
Infections and infestations
BRONCHITIS
|
0.39%
1/258
|
0.38%
1/260
|
0.38%
1/262
|
1.9%
5/260
|
|
Infections and infestations
INFLUENZA
|
0.78%
2/258
|
1.2%
3/260
|
0.38%
1/262
|
0.77%
2/260
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.39%
1/258
|
1.2%
3/260
|
0.76%
2/262
|
0.77%
2/260
|
|
Infections and infestations
NASOPHARYNGITIS
|
6.6%
17/258
|
3.1%
8/260
|
1.9%
5/262
|
2.3%
6/260
|
|
Infections and infestations
SINUSITIS
|
0.39%
1/258
|
0.00%
0/260
|
1.9%
5/262
|
0.00%
0/260
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
1.9%
5/258
|
1.2%
3/260
|
3.1%
8/262
|
2.3%
6/260
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
1.9%
5/258
|
3.1%
8/260
|
4.2%
11/262
|
3.8%
10/260
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.78%
2/258
|
0.38%
1/260
|
1.1%
3/262
|
1.5%
4/260
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
0.78%
2/258
|
1.2%
3/260
|
0.76%
2/262
|
1.5%
4/260
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
1.9%
5/258
|
1.9%
5/260
|
0.38%
1/262
|
0.38%
1/260
|
|
Nervous system disorders
DIZZINESS
|
1.6%
4/258
|
0.77%
2/260
|
0.76%
2/262
|
0.38%
1/260
|
|
Nervous system disorders
HEADACHE
|
2.3%
6/258
|
1.9%
5/260
|
2.7%
7/262
|
2.3%
6/260
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
17.8%
46/258
|
20.0%
52/260
|
23.3%
61/262
|
22.7%
59/260
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
1.9%
5/258
|
1.5%
4/260
|
1.9%
5/262
|
2.7%
7/260
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/258
|
0.77%
2/260
|
0.38%
1/262
|
3.1%
8/260
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
0.00%
0/258
|
0.00%
0/260
|
0.38%
1/262
|
1.2%
3/260
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
1.2%
3/258
|
1.5%
4/260
|
1.5%
4/262
|
1.2%
3/260
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
0.00%
0/258
|
0.77%
2/260
|
1.1%
3/262
|
0.00%
0/260
|
|
Vascular disorders
HYPERTENSION
|
2.7%
7/258
|
1.2%
3/260
|
0.00%
0/262
|
1.2%
3/260
|
Additional Information
Study Director
Novartis Pharmaceuticals
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