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 NCT01712516)
NCT ID: NCT01712516
Last Updated: 2015-07-15
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
1001 participants
baseline (BL), 12 weeks
2015-07-15
Participant Flow
Participants were randomized to each treatment arm in a 1:1:1:1 ratio.
One thousand one participants were randomized. (One participant was randomized twice, took study drug twice and was counted twice in the randomized and safety sets). 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
|
250
|
251
|
251
|
249
|
|
Overall Study
Safety Set
|
250
|
251
|
251
|
248
|
|
Overall Study
Full Analysis Set
|
250
|
251
|
250
|
247
|
|
Overall Study
COMPLETED
|
244
|
241
|
245
|
236
|
|
Overall Study
NOT COMPLETED
|
6
|
10
|
6
|
13
|
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
Technical problems
|
0
|
0
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
2
|
1
|
|
Overall Study
Death
|
0
|
1
|
0
|
0
|
|
Overall Study
Protocol deviation
|
1
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
2
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
9
|
3
|
9
|
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=250 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=251 Participants
12.5 ug b.i.d.
|
Placebo
n=249 Participants
b.i.d.
|
Total
n=1001 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
62.8 Years
STANDARD_DEVIATION 8.46 • n=5 Participants
|
63.7 Years
STANDARD_DEVIATION 8.58 • n=7 Participants
|
63.1 Years
STANDARD_DEVIATION 8.53 • n=5 Participants
|
62.5 Years
STANDARD_DEVIATION 8.07 • n=4 Participants
|
63.0 Years
STANDARD_DEVIATION 8.41 • n=21 Participants
|
|
Sex: Female, Male
Female
|
96 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
111 Participants
n=4 Participants
|
415 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
154 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
138 Participants
n=4 Participants
|
586 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=249 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=250 Participants
12.5 ug b.i.d.
|
Placebo
n=246 Participants
b.i.d.
|
|---|---|---|---|---|
|
Primary: Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))
|
0.234 Liters
Standard Error 0.0134
|
0.122 Liters
Standard Error 0.0134
|
0.155 Liters
Standard Error 0.0134
|
-0.028 Liters
Standard Error 0.0137
|
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=238 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=234 Participants
27.5 ug b.i.d.
|
NVA237
n=237 Participants
12.5 ug b.i.d.
|
Placebo
n=226 Participants
b.i.d.
|
|---|---|---|---|---|
|
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
|
-7.5 score on a scale
Standard Error 0.85
|
-5.9 score on a scale
Standard Error 0.86
|
-6.0 score on a scale
Standard Error 0.86
|
-1.1 score on a scale
Standard Error 0.88
|
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=238 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=234 Participants
27.5 ug b.i.d.
|
NVA237
n=237 Participants
12.5 ug b.i.d.
|
Placebo
n=226 Participants
b.i.d.
|
|---|---|---|---|---|
|
Percentage of Participants With a Clinically Important Improvement of at Least 4 Units in the SGRQ Total Score
|
59.2 Percentage of participants
|
56.8 Percentage of participants
|
51.5 Percentage of participants
|
34.5 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=246 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=249 Participants
12.5 ug b.i.d.
|
Placebo
n=245 Participants
b.i.d.
|
|---|---|---|---|---|
|
Change From Baseline in Trough FEV1
day 2
|
0.208 Liters
Standard Error 0.0107
|
0.111 Liters
Standard Error 0.0106
|
0.132 Liters
Standard Error 0.0107
|
0.010 Liters
Standard Error 0.0107
|
|
Change From Baseline in Trough FEV1
day 86
|
0.216 Liters
Standard Error 0.0142
|
0.138 Liters
Standard Error 0.0141
|
0.128 Liters
Standard Error 0.0142
|
-0.017 Liters
Standard Error 0.0145
|
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=243 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=249 Participants
27.5 ug b.i.d.
|
NVA237
n=246 Participants
12.5 ug b.i.d.
|
Placebo
n=241 Participants
b.i.d.
|
|---|---|---|---|---|
|
Change From Baseline in Pre-dose Trough FEV1
|
0.193 Liters
Standard Error 0.0132
|
0.100 Liters
Standard Error 0.0132
|
0.108 Liters
Standard Error 0.0133
|
-0.027 Liters
Standard Error 0.0135
|
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; 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=250 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=250 Participants
12.5 ug b.i.d.
|
Placebo
n=247 Participants
b.i.d.
|
|---|---|---|---|---|
|
Change From Baseline in FEV1
day 1, 5 min (n=248,249,249,243)
|
0.117 Liters
Standard Error 0.0061
|
0.076 Liters
Standard Error 0.0060
|
0.072 Liters
Standard Error 0.0061
|
-0.001 Liters
Standard Error 0.0062
|
|
Change From Baseline in FEV1
day 1, 15 min (n=248,251,249,244)
|
0.160 Liters
Standard Error 0.0070
|
0.090 Liters
Standard Error 0.0069
|
0.126 Liters
Standard Error 0.0070
|
0.005 Liters
Standard Error 0.0070
|
|
Change From Baseline in FEV1
day 1, 4 h (n=247,247,248,237)
|
0.220 Liters
Standard Error 0.0099
|
0.108 Liters
Standard Error 0.0099
|
0.167 Liters
Standard Error 0.0099
|
0.019 Liters
Standard Error 0.0101
|
|
Change From Baseline in FEV1
day 1, 6 h (n=247,246,244,239)
|
0.181 Liters
Standard Error 0.0103
|
0.085 Liters
Standard Error 0.0104
|
0.135 Liters
Standard Error 0.0104
|
-0.005 Liters
Standard Error 0.0106
|
|
Change From Baseline in FEV1
day 1, 11 h 55 min(n=242,243,244,239)
|
0.116 Liters
Standard Error 0.0114
|
0.029 Liters
Standard Error 0.0114
|
0.066 Liters
Standard Error 0.0114
|
-0.045 Liters
Standard Error 0.0115
|
|
Change From Baseline in FEV1
day 15, - 45 min (243,249,246,240)
|
0.208 Liters
Standard Error 0.0126
|
0.114 Liters
Standard Error 0.0124
|
0.108 Liters
Standard Error 0.0126
|
-0.045 Liters
Standard Error 0.0127
|
|
Change From Baseline in FEV1
day 15, -15 min (n=243,248,246,241)
|
0.238 Liters
Standard Error 0.0124
|
0.143 Liters
Standard Error 0.0123
|
0.132 Liters
Standard Error 0.0124
|
-0.025 Liters
Standard Error 0.0124
|
|
Change From Baseline in FEV1
day 15, 1 h (n=249,251,249,246)
|
0.321 Liters
Standard Error 0.0134
|
0.179 Liters
Standard Error 0.0133
|
0.212 Liters
Standard Error 0.0134
|
-0.019 Liters
Standard Error 0.0135
|
|
Change From Baseline in FEV1
day 29, -45 min (n=243,249,246,240)
|
0.213 Liters
Standard Error 0.0132
|
0.127 Liters
Standard Error 0.0131
|
0.117 Liters
Standard Error 0.0132
|
-0.030 Liters
Standard Error 0.0133
|
|
Change From Baseline in FEV1
day 29, -15 min (n=243,248,246,241)
|
0.235 Liters
Standard Error 0.0132
|
0.147 Liters
Standard Error 0.0131
|
0.138 Liters
Standard Error 0.0132
|
-0.013 Liters
Standard Error 0.0134
|
|
Change From Baseline in FEV1
day 57, -15 min (n=243,248,246,241)
|
0.224 Liters
Standard Error 0.0136
|
0.125 Liters
Standard Error 0.0135
|
0.147 Liters
Standard Error 0.0136
|
-0.014 Liters
Standard Error 0.0139
|
|
Change From Baseline in FEV1
day 57, 1 h (n=249,251,249,246)
|
0.319 Liters
Standard Error 0.0143
|
0.163 Liters
Standard Error 0.0143
|
0.221 Liters
Standard Error 0.0144
|
-0.016 Liters
Standard Error 0.0146
|
|
Change From Baseline in FEV1
day 85, -45 min (n=243,249,246,240)
|
0.187 Liters
Standard Error 0.0134
|
0.090 Liters
Standard Error 0.0135
|
0.096 Liters
Standard Error 0.0135
|
-0.032 Liters
Standard Error 0.0138
|
|
Change From Baseline in FEV1
day 85, - 15 min (n=243,248,246,241)
|
0.199 Liters
Standard Error 0.0138
|
0.109 Liters
Standard Error 0.0137
|
0.123 Liters
Standard Error 0.0138
|
-0.018 Liters
Standard Error 0.0141
|
|
Change From Baseline in FEV1
day 85, 5 min (n=248,249,249,243)
|
0.246 Liters
Standard Error 0.0142
|
0.151 Liters
Standard Error 0.0143
|
0.143 Liters
Standard Error 0.0142
|
-0.020 Liters
Standard Error 0.0144
|
|
Change From Baseline in FEV1
day 85, 15 min (n=248,251,249,244)
|
0.269 Liters
Standard Error 0.0141
|
0.153 Liters
Standard Error 0.0142
|
0.179 Liters
Standard Error 0.0141
|
-0.001 Liters
Standard Error 0.0145
|
|
Change From Baseline in FEV1
day 85, 1 h (n=249,251,249,246)
|
0.293 Liters
Standard Error 0.0144
|
0.141 Liters
Standard Error 0.0144
|
0.208 Liters
Standard Error 0.0144
|
-0.018 Liters
Standard Error 0.0147
|
|
Change From Baseline in FEV1
day 85, 2 h (n=249,249,248,246)
|
0.315 Liters
Standard Error 0.0146
|
0.159 Liters
Standard Error 0.0147
|
0.216 Liters
Standard Error 0.0148
|
-0.001 Liters
Standard Error 0.0150
|
|
Change From Baseline in FEV1
day 85, 4 h (n=247,247,248,237)
|
0.260 Liters
Standard Error 0.0150
|
0.145 Liters
Standard Error 0.0151
|
0.172 Liters
Standard Error 0.0151
|
-0.004 Liters
Standard Error 0.0157
|
|
Change From Baseline in FEV1
day 85, 6 h (n=247,246,244,239)
|
0.226 Liters
Standard Error 0.0149
|
0.122 Liters
Standard Error 0.0150
|
0.139 Liters
Standard Error 0.0151
|
-0.011 Liters
Standard Error 0.0155
|
|
Change From Baseline in FEV1
day 85, 8 h (n=248,247,245,242)
|
0.198 Liters
Standard Error 0.0146
|
0.107 Liters
Standard Error 0.0147
|
0.133 Liters
Standard Error 0.0149
|
-0.039 Liters
Standard Error 0.0153
|
|
Change From Baseline in FEV1
day 85, 11 h 55 min(n=242,243,244,239)
|
0.163 Liters
Standard Error 0.0147
|
0.078 Liters
Standard Error 0.0150
|
0.105 Liters
Standard Error 0.0150
|
-0.073 Liters
Standard Error 0.0154
|
|
Change From Baseline in FEV1
day 86, 23 h 15 min (n=241,246,245,241)
|
0.206 Liters
Standard Error 0.0148
|
0.130 Liters
Standard Error 0.0147
|
0.117 Liters
Standard Error 0.0149
|
-0.023 Liters
Standard Error 0.0150
|
|
Change From Baseline in FEV1
day 86, 23 h 45 min (n=246,251,248,244)
|
0.221 Liters
Standard Error 0.0144
|
0.144 Liters
Standard Error 0.0144
|
0.132 Liters
Standard Error 0.0146
|
-0.012 Liters
Standard Error 0.0149
|
|
Change From Baseline in FEV1
day 1, 1 h (n=249,251,249,246)
|
0.199 Liters
Standard Error 0.0082
|
0.089 Liters
Standard Error 0.0082
|
0.176 Liters
Standard Error 0.0083
|
0.008 Liters
Standard Error 0.0083
|
|
Change From Baseline in FEV1
day 1, 2 h (n=249,249,248,246)
|
0.237 Liters
Standard Error 0.0091
|
0.109 Liters
Standard Error 0.0091
|
0.197 Liters
Standard Error 0.0092
|
0.030 Liters
Standard Error 0.0092
|
|
Change From Baseline in FEV1
day 1, 8 h (n=248,247,245,242)
|
0.165 Liters
Standard Error 0.0102
|
0.077 Liters
Standard Error 0.0101
|
0.112 Liters
Standard Error 0.0103
|
-0.019 Liters
Standard Error 0.0104
|
|
Change From Baseline in FEV1
day 2, 23 h 15 min (n=241,246,245,241)
|
0.201 Liters
Standard Error 0.0111
|
0.105 Liters
Standard Error 0.0110
|
0.128 Liters
Standard Error 0.0111
|
0.002 Liters
Standard Error 0.0111
|
|
Change From Baseline in FEV1
day 2, 23 h 45 min (n= 246,251,248,244)
|
0.216 Liters
Standard Error 0.0111
|
0.118 Liters
Standard Error 0.0109
|
0.137 Liters
Standard Error 0.0111
|
0.018 Liters
Standard Error 0.0111
|
|
Change From Baseline in FEV1
day 29, 1 h (n=249,251,249,246)
|
0.320 Liters
Standard Error 0.0135
|
0.170 Liters
Standard Error 0.0135
|
0.216 Liters
Standard Error 0.0136
|
-0.004 Liters
Standard Error 0.0137
|
|
Change From Baseline in FEV1
day 57, -45 min (n=243,249,246,240)
|
0.203 Liters
Standard Error 0.0136
|
0.104 Liters
Standard Error 0.0136
|
0.117 Liters
Standard Error 0.0137
|
-0.037 Liters
Standard Error 0.0140
|
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; 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=250 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=250 Participants
12.5 ug b.i.d.
|
Placebo
n=247 Participants
b.i.d.
|
|---|---|---|---|---|
|
Change From Baseline in FVC
day 1, 5 min (n=248,249,249,243)
|
0.245 Liters
Standard Error 0.0138
|
0.175 Liters
Standard Error 0.0136
|
0.158 Liters
Standard Error 0.0137
|
-0.006 Liters
Standard Error 0.0140
|
|
Change From Baseline in FVC
day 1, 15 min (n=248,251,249,244)
|
0.318 Liters
Standard Error 0.0154
|
0.185 Liters
Standard Error 0.0153
|
0.238 Liters
Standard Error 0.0155
|
0.009 Liters
Standard Error 0.0155
|
|
Change From Baseline in FVC
day 1, 1 h (n=249,251,249,246)
|
0.355 Liters
Standard Error 0.0165
|
0.153 Liters
Standard Error 0.0164
|
0.309 Liters
Standard Error 0.0166
|
0.013 Liters
Standard Error 0.0166
|
|
Change From Baseline in FVC
day 1, 2 h (n=249,249,248,246)
|
0.395 Liters
Standard Error 0.0181
|
0.214 Liters
Standard Error 0.0180
|
0.324 Liters
Standard Error 0.0182
|
0.044 Liters
Standard Error 0.0183
|
|
Change From Baseline in FVC
day 1, 4 h (n=247,247,248,237)
|
0.364 Liters
Standard Error 0.0187
|
0.189 Liters
Standard Error 0.0187
|
0.271 Liters
Standard Error 0.0188
|
0.026 Liters
Standard Error 0.0192
|
|
Change From Baseline in FVC
day 1, 6 h (n=247,246,244,239)
|
0.316 Liters
Standard Error 0.0186
|
0.159 Liters
Standard Error 0.0188
|
0.244 Liters
Standard Error 0.0189
|
0.004 Liters
Standard Error 0.0192
|
|
Change From Baseline in FVC
day 1, 8 h (n=248,247,245,242)
|
0.285 Liters
Standard Error 0.0179
|
0.154 Liters
Standard Error 0.0178
|
0.212 Liters
Standard Error 0.0182
|
-0.021 Liters
Standard Error 0.0183
|
|
Change From Baseline in FVC
day 1, 11 h 55 min (n=242,243,244,239)
|
0.235 Liters
Standard Error 0.0188
|
0.093 Liters
Standard Error 0.0188
|
0.125 Liters
Standard Error 0.0188
|
-0.060 Liters
Standard Error 0.0190
|
|
Change From Baseline in FVC
day 2, 23 h 15 min (n=241,246,245,241)
|
0.343 Liters
Standard Error 0.0193
|
0.191 Liters
Standard Error 0.0191
|
0.217 Liters
Standard Error 0.0194
|
0.001 Liters
Standard Error 0.0194
|
|
Change From Baseline in FVC
day 2, 23 h 45 min (n=246,251,248,244)
|
0.355 Liters
Standard Error 0.0195
|
0.196 Liters
Standard Error 0.0192
|
0.229 Liters
Standard Error 0.0194
|
0.027 Liters
Standard Error 0.0195
|
|
Change From Baseline in FVC
day 15, -45 min (n=243,249,246,240)
|
0.313 Liters
Standard Error 0.0205
|
0.163 Liters
Standard Error 0.0201
|
0.168 Liters
Standard Error 0.0204
|
-0.047 Liters
Standard Error 0.0206
|
|
Change From Baseline in FVC
day 15, 1 h (n=249,251,249,246)
|
0.473 Liters
Standard Error 0.0025
|
0.269 Liters
Standard Error 0.0223
|
0.311 Liters
Standard Error 0.0225
|
-0.009 Liters
Standard Error 0.0227
|
|
Change From Baseline in FVC
day 29, 1 h (n=249,251,249,246)
|
0.449 Liters
Standard Error 0.0224
|
0.259 Liters
Standard Error 0.0223
|
0.322 Liters
Standard Error 0.0225
|
0.008 Liters
Standard Error 0.0227
|
|
Change From Baseline in FVC
day 57, -15 min (n=243,248,246,241)
|
0.298 Liters
Standard Error 0.0223
|
0.167 Liters
Standard Error 0.0222
|
0.222 Liters
Standard Error 0.0224
|
-0.009 Liters
Standard Error 0.0229
|
|
Change From Baseline in FVC
day 85, -45 min (n=243,249,246,240)
|
0.252 Liters
Standard Error 0.0223
|
0.121 Liters
Standard Error 0.0224
|
0.143 Liters
Standard Error 0.0225
|
-0.029 Liters
Standard Error 0.0229
|
|
Change From Baseline in FVC
day 85, -15 min (n=243,248,246,241)
|
0.263 Liters
Standard Error 0.0224
|
0.142 Liters
Standard Error 0.0223
|
0.180 Liters
Standard Error 0.0225
|
-0.031 Liters
Standard Error 0.0229
|
|
Change From Baseline in FVC
day 85, 5 min (n=248,249,249,243)
|
0.331 Liters
Standard Error 0.0243
|
0.215 Liters
Standard Error 0.0244
|
0.225 Liters
Standard Error 0.0243
|
-0.048 Liters
Standard Error 0.0247
|
|
Change From Baseline in FVC
day 85, 15 min (n=248,251,249,244)
|
0.377 Liters
Standard Error 0.0242
|
0.223 Liters
Standard Error 0.0243
|
0.276 Liters
Standard Error 0.0243
|
-0.004 Liters
Standard Error 0.0248
|
|
Change From Baseline in FVC
day 85, 2h (n=249,249,248,246)
|
0.414 Liters
Standard Error 0.0244
|
0.218 Liters
Standard Error 0.0245
|
0.301 Liters
Standard Error 0.0247
|
-0.001 Liters
Standard Error 0.0251
|
|
Change From Baseline in FVC
day 85, 4 h (n=247,247,248,237)
|
0.338 Liters
Standard Error 0.0247
|
0.203 Liters
Standard Error 0.0249
|
0.261 Liters
Standard Error 0.0250
|
0.002 Liters
Standard Error 0.0259
|
|
Change From Baseline in FVC
day 86, 23 h 45 min (n=246,251,248,244)
|
0.298 Liters
Standard Error 0.0240
|
0.199 Liters
Standard Error 0.0239
|
0.210 Liters
Standard Error 0.0244
|
-0.017 Liters
Standard Error 0.0248
|
|
Change From Baseline in FVC
day 15, -15 min (n=243,248,246,241)
|
0.358 Liters
Standard Error 0.0207
|
0.201 Liters
Standard Error 0.0204
|
0.198 Liters
Standard Error 0.0207
|
-0.020 Liters
Standard Error 0.0207
|
|
Change From Baseline in FVC
day 29, -45 min (n=243,249,246,240)
|
0.320 Liters
Standard Error 0.0217
|
0.194 Liters
Standard Error 0.0216
|
0.188 Liters
Standard Error 0.0217
|
-0.025 Liters
Standard Error 0.0220
|
|
Change From Baseline in FVC
day 29, -15 min (n=243,248,246,241)
|
0.332 Liters
Standard Error 0.0216
|
0.218 Liters
Standard Error 0.0215
|
0.197 Liters
Standard Error 0.0216
|
-0.004 Liters
Standard Error 0.0219
|
|
Change From Baseline in FVC
day 57, -45 min (n=243,249,246,240)
|
0.293 Liters
Standard Error 0.0215
|
0.142 Liters
Standard Error 0.0215
|
0.173 Liters
Standard Error 0.0217
|
-0.034 Liters
Standard Error 0.0221
|
|
Change From Baseline in FVC
day 57, 1 h (n=249,251,249,246)
|
0.445 Liters
Standard Error 0.0233
|
0.227 Liters
Standard Error 0.0233
|
0.326 Liters
Standard Error 0.0234
|
-0.011 Liters
Standard Error 0.0238
|
|
Change From Baseline in FVC
day 85, 1 h (n=249,251,249,246)
|
0.400 Liters
Standard Error 0.0243
|
0.209 Liters
Standard Error 0.0243
|
0.295 Liters
Standard Error 0.0244
|
-0.023 Liters
Standard Error 0.0248
|
|
Change From Baseline in FVC
day 85, 6 h (n=247,246,244,239)
|
0.305 Liters
Standard Error 0.0239
|
0.164 Liters
Standard Error 0.0240
|
0.211 Liters
Standard Error 0.0241
|
-0.011 Liters
Standard Error 0.0248
|
|
Change From Baseline in FVC
day 85, 8 h (n=248,247,245,242)
|
0.273 Liters
Standard Error 0.0233
|
0.152 Liters
Standard Error 0.0235
|
0.213 Liters
Standard Error 0.0237
|
-0.038 Liters
Standard Error 0.0244
|
|
Change From Baseline in FVC
day 85, 11 55 min (n=242,243,244,239)
|
0.233 Liters
Standard Error 0.0239
|
0.131 Liters
Standard Error 0.0243
|
0.197 Liters
Standard Error 0.0243
|
-0.093 Liters
Standard Error 0.0250
|
|
Change From Baseline in FVC
day 86, 23 h 15 min (n=241,246,245,241)
|
0.278 Liters
Standard Error 0.0248
|
0.172 Liters
Standard Error 0.0247
|
0.176 Liters
Standard Error 0.0250
|
-0.021 Liters
Standard Error 0.0251
|
SECONDARY outcome
Timeframe: BL, day 1, 12 weeksPopulation: 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=250 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=250 Participants
12.5 ug b.i.d.
|
Placebo
n=247 Participants
b.i.d.
|
|---|---|---|---|---|
|
Secondary: 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, AUC 4-8h (n=248,248,250,243)
|
0.187 Liters
Standard Error 0.0093
|
0.090 Liters
Standard Error 0.0093
|
0.134 Liters
Standard Error 0.0093
|
-0.003 Liters
Standard Error 0.0095
|
|
Secondary: 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, AUC 4-8h (n=248,248,250,243)
|
0.229 Liters
Standard Error 0.0140
|
0.120 Liters
Standard Error 0.0141
|
0.148 Liters
Standard Error 0.0141
|
-0.021 Liters
Standard Error 0.0145
|
|
Secondary: 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, AUC 8-12h (n=248,249,249,245)
|
0.182 Liters
Standard Error 0.0141
|
0.095 Liters
Standard Error 0.0142
|
0.123 Liters
Standard Error 0.0143
|
-0.055 Liters
Standard Error 0.0146
|
|
Secondary: 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, AUC 8-12h (n=248,249,249,245)
|
0.143 Liters
Standard Error 0.0099
|
0.054 Liters
Standard Error 0.0099
|
0.092 Liters
Standard Error 0.0100
|
-0.031 Liters
Standard Error 0.0101
|
|
Secondary: 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, AUC 0-4h (n=249,251,250,246)
|
0.213 Liters
Standard Error 0.0077
|
0.101 Liters
Standard Error 0.0077
|
0.174 Liters
Standard Error 0.0077
|
0.019 Liters
Standard Error 0.0078
|
|
Secondary: 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, AUC 0-12h (n=249,251,250,246)
|
0.184 Liters
Standard Error 0.0084
|
0.080 Liters
Standard Error 0.0084
|
0.135 Liters
Standard Error 0.0084
|
-0.003 Liters
Standard Error 0.0085
|
|
Secondary: 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, AUC 0-4h (n=249,251,250,246)
|
0.289 Liters
Standard Error 0.0138
|
0.147 Liters
Standard Error 0.0138
|
0.196 Liters
Standard Error 0.0138
|
-0.008 Liters
Standard Error 0.0141
|
|
Secondary: 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, AUC 0-12h (n=249,251,250,246)
|
0.234 Liters
Standard Error 0.0134
|
0.122 Liters
Standard Error 0.0134
|
0.155 Liters
Standard Error 0.0134
|
-0.028 Liters
Standard Error 0.0137
|
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=233 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=238 Participants
27.5 ug b.i.d.
|
NVA237
n=232 Participants
12.5 ug b.i.d.
|
Placebo
n=222 Participants
b.i.d.
|
|---|---|---|---|---|
|
Transitional Dyspnea Index (TDI) Focal Score
|
2.88 score on a scale
Standard Error 0.251
|
1.98 score on a scale
Standard Error 0.252
|
1.88 score on a scale
Standard Error 0.252
|
0.85 score on a scale
Standard Error 0.256
|
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=243 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=242 Participants
27.5 ug b.i.d.
|
NVA237
n=242 Participants
12.5 ug b.i.d.
|
Placebo
n=235 Participants
b.i.d.
|
|---|---|---|---|---|
|
Secondary: Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
|
-2.19 number of puffs
Standard Error 0.150
|
-2.05 number of puffs
Standard Error 0.150
|
-1.78 number of puffs
Standard Error 0.151
|
-1.04 number of puffs
Standard Error 0.153
|
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=250 Participants
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 Participants
27.5 ug b.i.d.
|
NVA237
n=250 Participants
12.5 ug b.i.d.
|
Placebo
n=247 Participants
b.i.d.
|
|---|---|---|---|---|
|
Secondary: Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
total daily (n=243,242,242,235)
|
-1.34 score on a scale
Standard Error 0.108
|
-1.22 score on a scale
Standard Error 0.108
|
-1.09 score on a scale
Standard Error 0.108
|
-0.61 score on a scale
Standard Error 0.110
|
|
Secondary: Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
total daytime (n=242,239,240,234)
|
-1.16 score on a scale
Standard Error 0.105
|
-1.05 score on a scale
Standard Error 0.105
|
-0.96 score on a scale
Standard Error 0.105
|
-0.53 score on a scale
Standard Error 0.106
|
|
Secondary: Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
total nighttime (n=243,239,238,234)
|
-1.09 score on a scale
Standard Error 0.107
|
-1.01 score on a scale
Standard Error 0.107
|
-0.90 score on a scale
Standard Error 0.108
|
-0.41 score on a scale
Standard Error 0.109
|
Adverse Events
QVA149
QAB149
NVA237
Placebo
Serious adverse events
| Measure |
QVA149
n=250 participants at risk
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 participants at risk
27.5 ug b.i.d.
|
NVA237
n=251 participants at risk
12.5 ug b.i.d.
|
Placebo
n=248 participants at risk
b.i.d.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/250
|
0.40%
1/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Cardiac disorders
CARDIOPULMONARY FAILURE
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.40%
1/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Gastrointestinal disorders
PNEUMOPERITONEUM
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
General disorders
CHEST PAIN
|
0.40%
1/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
General disorders
OEDEMA PERIPHERAL
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
|
0.00%
0/250
|
0.40%
1/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Infections and infestations
EPIGLOTTITIS
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.00%
0/250
|
0.40%
1/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Infections and infestations
PERIRECTAL ABSCESS
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Infections and infestations
PNEUMONIA
|
0.40%
1/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Infections and infestations
SINUSITIS
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Injury, poisoning and procedural complications
FEMUR FRACTURE
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.40%
1/248
|
|
Injury, poisoning and procedural complications
GUN SHOT WOUND
|
0.00%
0/250
|
0.40%
1/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Investigations
HEPATIC ENZYME INCREASED
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.00%
0/250
|
0.40%
1/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.40%
1/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC CANCER
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC MALIGNANT MELANOMA
|
0.40%
1/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NON-SMALL CELL LUNG CANCER
|
0.40%
1/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA OF SKIN
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.40%
1/250
|
0.40%
1/251
|
2.0%
5/251
|
2.8%
7/248
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Respiratory, thoracic and mediastinal disorders
LUNG INFILTRATION
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
0.40%
1/248
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.00%
0/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
Other adverse events
| Measure |
QVA149
n=250 participants at risk
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
|
QAB149
n=251 participants at risk
27.5 ug b.i.d.
|
NVA237
n=251 participants at risk
12.5 ug b.i.d.
|
Placebo
n=248 participants at risk
b.i.d.
|
|---|---|---|---|---|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
1.2%
3/250
|
0.00%
0/251
|
0.00%
0/251
|
0.00%
0/248
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/250
|
0.00%
0/251
|
1.2%
3/251
|
0.40%
1/248
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/250
|
0.40%
1/251
|
1.2%
3/251
|
0.00%
0/248
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.80%
2/250
|
0.40%
1/251
|
0.00%
0/251
|
1.2%
3/248
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/250
|
0.40%
1/251
|
0.80%
2/251
|
1.6%
4/248
|
|
Immune system disorders
SEASONAL ALLERGY
|
1.2%
3/250
|
0.00%
0/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Infections and infestations
BRONCHITIS
|
1.2%
3/250
|
2.0%
5/251
|
2.0%
5/251
|
1.2%
3/248
|
|
Infections and infestations
INFLUENZA
|
0.80%
2/250
|
1.6%
4/251
|
0.40%
1/251
|
0.40%
1/248
|
|
Infections and infestations
NASOPHARYNGITIS
|
1.6%
4/250
|
2.0%
5/251
|
2.8%
7/251
|
1.2%
3/248
|
|
Infections and infestations
PHARYNGITIS
|
1.2%
3/250
|
0.40%
1/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Infections and infestations
SINUSITIS
|
0.00%
0/250
|
1.2%
3/251
|
0.80%
2/251
|
0.81%
2/248
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
2.4%
6/250
|
1.2%
3/251
|
3.6%
9/251
|
2.8%
7/248
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
1.2%
3/250
|
2.4%
6/251
|
0.80%
2/251
|
2.4%
6/248
|
|
Infections and infestations
URINARY TRACT INFECTION
|
1.2%
3/250
|
0.00%
0/251
|
1.6%
4/251
|
0.81%
2/248
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
1.6%
4/250
|
0.80%
2/251
|
1.2%
3/251
|
2.0%
5/248
|
|
Injury, poisoning and procedural complications
CONTUSION
|
0.80%
2/250
|
1.2%
3/251
|
0.40%
1/251
|
0.40%
1/248
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
1.6%
4/250
|
0.80%
2/251
|
0.40%
1/251
|
0.81%
2/248
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.00%
0/250
|
0.40%
1/251
|
0.00%
0/251
|
1.2%
3/248
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/250
|
0.00%
0/251
|
1.2%
3/251
|
0.00%
0/248
|
|
Nervous system disorders
HEADACHE
|
0.40%
1/250
|
2.0%
5/251
|
0.80%
2/251
|
1.6%
4/248
|
|
Psychiatric disorders
INSOMNIA
|
1.2%
3/250
|
0.40%
1/251
|
0.40%
1/251
|
0.00%
0/248
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
11.2%
28/250
|
9.2%
23/251
|
9.2%
23/251
|
14.5%
36/248
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
1.2%
3/250
|
1.2%
3/251
|
0.40%
1/251
|
2.4%
6/248
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
1.2%
3/248
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
2.0%
5/250
|
0.00%
0/251
|
1.6%
4/251
|
1.2%
3/248
|
|
Respiratory, thoracic and mediastinal disorders
SPUTUM INCREASED
|
0.00%
0/250
|
0.00%
0/251
|
0.00%
0/251
|
1.2%
3/248
|
|
Vascular disorders
HYPERTENSION
|
1.2%
3/250
|
0.80%
2/251
|
1.2%
3/251
|
1.6%
4/248
|
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