Trial Outcomes & Findings for Efficacy, Safety and Tolerability of the Co-administration of NVA237 Plus Indacaterol Once Daily Versus Indacaterol Once Daily in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01604278)
NCT ID: NCT01604278
Last Updated: 2014-11-14
Results Overview
Centralized spirometry according to internationally accepted standards was used. The model contained treatment, baseline smoking status and baseline inhaled corticosteroid (ICS) use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilator as covariates and center nested in region as a random effect. If trough FEV1 was missing at week 12, the latest non-missing pre-dose trough FEV1 (the mean of 45 and 15 min pre-dose measurements) from day 29, 57 or 84) was carried forward. These measurements had to have been taken before the next dose of study medication. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
COMPLETED
PHASE3
449 participants
12 weeks
2014-11-14
Participant Flow
The number of patients randomized was 449. Of these participants, the Full Analysis Set (FAS) comprised 446 participants who received at least one dose of study drug and had no major deviations which led to removal from the FAS. The Safety Set included 447 participants who received at least one dose of study drug.
Participant milestones
| Measure |
NVA237 + Indacaterol
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Overall Study
STARTED
|
226
|
223
|
|
Overall Study
Safety Set
|
226
|
221
|
|
Overall Study
Full Analysis Set
|
226
|
220
|
|
Overall Study
COMPLETED
|
212
|
210
|
|
Overall Study
NOT COMPLETED
|
14
|
13
|
Reasons for withdrawal
| Measure |
NVA237 + Indacaterol
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Administrative problems
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Adverse Event
|
3
|
5
|
|
Overall Study
Protocol Deviation
|
5
|
3
|
Baseline Characteristics
Efficacy, Safety and Tolerability of the Co-administration of NVA237 Plus Indacaterol Once Daily Versus Indacaterol Once Daily in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
NVA237 + Indacaterol
n=226 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=221 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
Total
n=447 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.4 Years
STANDARD_DEVIATION 8.44 • n=5 Participants
|
64.1 Years
STANDARD_DEVIATION 7.67 • n=7 Participants
|
63.7 Years
STANDARD_DEVIATION 8.07 • n=5 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
180 Participants
n=5 Participants
|
186 Participants
n=7 Participants
|
366 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Centralized spirometry according to internationally accepted standards was used. The model contained treatment, baseline smoking status and baseline inhaled corticosteroid (ICS) use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilator as covariates and center nested in region as a random effect. If trough FEV1 was missing at week 12, the latest non-missing pre-dose trough FEV1 (the mean of 45 and 15 min pre-dose measurements) from day 29, 57 or 84) was carried forward. These measurements had to have been taken before the next dose of study medication. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=214 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=214 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Trough Forced Expiratory Volume at 1 Second (FEV1)
|
1.499 Liters
Standard Error 0.0135
|
1.436 Liters
Standard Error 0.0136
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Centralized spirometry was used according to internationally accepted standards was used. The trapezoidal rule was applied to calculate FEV1 Area Under the Curve (AUC) and then normalized to the length of time. Whether the participants had complete or incomplete FEV1 assessments in respective time ranges, their AUCs were calculated based on the existing FEV1 measurements (i.e., the missing FEV1 measurements were not interpolated). Specifically, for those participants who had a FEV1 assessment at only one time-point, their AUC was approximated by the observed FEV1. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=208 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=208 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
FEV(1) Area Under the Curve (AUC) During 30 Minutes to 4 Hours Post Dose
|
1.641 Liters
Standard Error 0.0132
|
1.530 Liters
Standard Error 0.0134
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Centralized spirometry was used according to internationally accepted standards was used. Peak FEV1 was defined as the maximum FEV1 during the first 4 hours post morning dosing. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilator as covariates and center nested in a region as a random effect. If all FEV1 measurements were missing from 30 minutes onward, the peak FEV1 was not calculated. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=208 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=208 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Peak FEV1 During 30 Minutes to 4 Hours Post-dose at 12 Weeks
|
1.702 Liters
Standard Error 0.0137
|
1.596 Liters
Standard Error 0.0138
|
SECONDARY outcome
Timeframe: Day 1, Day 29, Day 57 and Days 84/85Population: Full Analysis Set
Centralized spirometry according to internationally accepted standards was used. FEV1 was measured at all post-dose time points up to 4 hours, and at 23 hours 15 minutes and 23 hours 45 minutes, by visit. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhaltion of short acting bronchodilators and FEV1 post inhaltion of short acting bronchodilators as covariates and center nested in region as a random effect. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=226 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=220 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
FEV1 at Individual Time-points
Day 1, 30 minutes (min) post dose (n=208,199)
|
1.544 Liters
Standard Error 0.0086
|
1.467 Liters
Standard Error 0.0088
|
|
FEV1 at Individual Time-points
Day 1, 1 hour (h) post dose (n=214,209)
|
1.589 Liters
Standard Error 0.0102
|
1.479 Liters
Standard Error 0.0104
|
|
FEV1 at Individual Time-points
Day 1, 2 h post dose (n=212,207)
|
1.626 Liters
Standard Error 0.0114
|
1.506 Liters
Standard Error 0.0117
|
|
FEV1 at Individual Time-points
Day 1, 4 h post dose (n=206,213)
|
1.630 Liters
Standard Error 0.0122
|
1.518 Liters
Standard Error 0.0122
|
|
FEV1 at Individual Time-points
Day 1, 23 h 15 min post dose (n=201,203)
|
1.481 Liters
Standard Error 0.0118
|
1.409 Liters
Standard Error 0.0118
|
|
FEV1 at Individual Time-points
Day 1, 23 h 45 min post dose (n=213,204)
|
1.502 Liters
Standard Error 0.0109
|
1.425 Liters
Standard Error 0.0112
|
|
FEV1 at Individual Time-points
Day 29, 45 min pre-dose (n=198,202)
|
1.491 Liters
Standard Error 0.0150
|
1.438 Liters
Standard Error 0.0150
|
|
FEV1 at Individual Time-points
Day 29, 15 min pre-dose (n=198,200)
|
1.524 Liters
Standard Error 0.0156
|
1.470 Liters
Standard Error 0.0155
|
|
FEV1 at Individual Time-points
Day 29, 30 min post dose (n=202,201)
|
1.617 Liters
Standard Error 0.0152
|
1.508 Liters
Standard Error 0.0154
|
|
FEV1 at Individual Time-points
Day 29, 1 h post dose (n=200,199)
|
1.648 Liters
Standard Error 0.0144
|
1.524 Liters
Standard Error 0.0145
|
|
FEV1 at Individual Time-points
Day 56, 45 min pre-dose (n=201,202)
|
1.482 Liters
Standard Error 0.0145
|
1.418 Liters
Standard Error 0.0146
|
|
FEV1 at Individual Time-points
Day 56, 15 min pre-dose (n=199,198)
|
1.509 Liters
Standard Error 0.0148
|
1.443 Liters
Standard Error 0.0149
|
|
FEV1 at Individual Time-points
Day 56, 30 min post dose (n=200,200)
|
1.606 Liters
Standard Error 0.0144
|
1.495 Liters
Standard Error 0.0146
|
|
FEV1 at Individual Time-points
Day 56, 1 h post dose (n=197,204)
|
1.634 Liters
Standard Error 0.0149
|
1.520 Liters
Standard Error 0.0148
|
|
FEV1 at Individual Time-points
Days 84/85, 45 min pre-dose (n=201,206)
|
1.459 Liters
Standard Error 0.0127
|
1.411 Liters
Standard Error 0.0126
|
|
FEV1 at Individual Time-points
Days 84/85, 15 min pre-dose (n=190,196)
|
1.476 Liters
Standard Error 0.0129
|
1.439 Liters
Standard Error 0.0129
|
|
FEV1 at Individual Time-points
Days 84/85, 30 min post dose (n=198,199)
|
1.604 Liters
Standard Error 0.0125
|
1.514 Liters
Standard Error 0.0126
|
|
FEV1 at Individual Time-points
Days 84/85, 1 h post dose (n=201,200)
|
1.638 Liters
Standard Error 0.0125
|
1.514 Liters
Standard Error 0.0126
|
|
FEV1 at Individual Time-points
Days 84/85, 2 h post dose (n=198,201)
|
1.665 Liters
Standard Error 0.0139
|
1.542 Liters
Standard Error 0.0139
|
|
FEV1 at Individual Time-points
Days 84/85, 23 h 15 min post dose (n=193,188)
|
1.474 Liters
Standard Error 0.0139
|
1.426 Liters
Standard Error 0.0143
|
|
FEV1 at Individual Time-points
Days 84/85, 23 h 45 min post dose (n=197,199)
|
1.508 Liters
Standard Error 0.0147
|
1.452 Liters
Standard Error 0.0148
|
|
FEV1 at Individual Time-points
Days 84/85, 4 h post dose (n=200,198)
|
1.620 Liters
Standard Error 0.0162
|
1.529 Liters
Standard Error 0.0165
|
SECONDARY outcome
Timeframe: Day 1, Day 29, Day 57 and Days 84/85Population: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 15 minutes and 23 hours 45 minutes, by visit. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of FVC, FEV1 prior to inhaltion of short acting bronchodilators and FEV1 post inhaltion of short acting bronchodilators as covariates and center nested in region as a random effect. FVC measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were set to missing.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=226 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=220 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 1, 30 min post dose (n=208,199)
|
3.214 Liters
Standard Error 0.0181
|
3.135 Liters
Standard Error 0.0186
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 1, 1 h post dose (n=214,209)
|
3.295 Liters
Standard Error 0.0260
|
3.182 Liters
Standard Error 0.0264
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 1, 2 h post dose (n=212,207)
|
3.325 Liters
Standard Error 0.0229
|
3.200 Liters
Standard Error 0.0234
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 1, 4 h post dose (n=206,213)
|
3.340 Liters
Standard Error 0.0239
|
3.218 Liters
Standard Error 0.0238
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 1, 23 h 15 min post dose (n=201,203)
|
3.155 Liters
Standard Error 0.0267
|
3.039 Liters
Standard Error 0.0268
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 1, 23 h 45 min post dose (n=213,204)
|
3.201 Liters
Standard Error 0.0257
|
3.095 Liters
Standard Error 0.0263
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 29, 45 min pre-dose (n=198,202)
|
3.146 Liters
Standard Error 0.0299
|
3.043 Liters
Standard Error 0.0299
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 29, 15 min pre-dose (n=198,200)
|
3.184 Liters
Standard Error 0.0315
|
3.092 Liters
Standard Error 0.0314
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 29, 30 min post dose (n=202,201)
|
3.316 Liters
Standard Error 0.0338
|
3.201 Liters
Standard Error 0.0341
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 29, 1 h post dose (n=200,199)
|
3.362 Liters
Standard Error 0.0336
|
3.197 Liters
Standard Error 0.0337
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 56, 45 min pre-dose (n=201,202)
|
3.102 Liters
Standard Error 0.0302
|
3.015 Liters
Standard Error 0.0303
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 56, 15 min pre-dose (n=199,198)
|
3.156 Liters
Standard Error 0.0321
|
3.086 Liters
Standard Error 0.0322
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 56, 30 min post dose (n=200,200)
|
3.282 Liters
Standard Error 0.0316
|
3.190 Liters
Standard Error 0.0319
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Day 56, 1 h post dose (n=197,204)
|
3.327 Liters
Standard Error 0.0323
|
3.219 Liters
Standard Error 0.0321
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 45 min pre-dose (n=201,206)
|
3.052 Liters
Standard Error 0.0280
|
3.016 Liters
Standard Error 0.0279
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 30 min post dose (n=198,199)
|
3.246 Liters
Standard Error 0.0262
|
3.162 Liters
Standard Error 0.0264
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 4 h post dose (n=200,198)
|
3.251 Liters
Standard Error 0.0292
|
3.161 Liters
Standard Error 0.0297
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 23 h 15 min post dose (n=193,188)
|
3.123 Liters
Standard Error 0.0285
|
3.050 Liters
Standard Error 0.0292
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 23 h 45 min post dose (n=197,199)
|
3.136 Liters
Standard Error 0.0256
|
3.047 Liters
Standard Error 0.0258
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 15 min pre-dose (n=190,196)
|
3.064 Liters
Standard Error 0.0256
|
3.012 Liters
Standard Error 0.0254
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 1 h post dose (n=201,200)
|
3.312 Liters
Standard Error 0.0291
|
3.179 Liters
Standard Error 0.0294
|
|
Forced Vital Capacity (FVC) at Individual Time-points
Days 84/85, 2 h post dose (n=198,201)
|
3.318 Liters
Standard Error 0.0261
|
3.181 Liters
Standard Error 0.0261
|
SECONDARY outcome
Timeframe: Day 1, Days 84/85Population: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Inspiratory Capacity (IC) was measured at 20 min pre-dose and at post-dose at 25 minutes, 1 hour 55 minutes, 3 hours 55 minutes and 23 hours 40 minutes, by visit. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of IC, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilators as covariates and center nested in region as a random effect. IC measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were set to missing.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=226 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=220 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Inspiratory Capacity (IC) at Individual Time-points
Day 1, 25 min post dose (n=164,168)
|
2.493 Liters
Standard Error 0.0234
|
2.434 Liters
Standard Error 0.0231
|
|
Inspiratory Capacity (IC) at Individual Time-points
Day 1, 1 h 55 min (n=161,176)
|
2.587 Liters
Standard Error 0.0294
|
2.478 Liters
Standard Error 0.0287
|
|
Inspiratory Capacity (IC) at Individual Time-points
Days 84/85, 25 min post dose (n=149,145)
|
2.580 Liters
Standard Error 0.0372
|
2.420 Liters
Standard Error 0.0377
|
|
Inspiratory Capacity (IC) at Individual Time-points
Days 84/85, 1 h 55 min post dose (n=146,153)
|
2.607 Liters
Standard Error 0.0388
|
2.485 Liters
Standard Error 0.0384
|
|
Inspiratory Capacity (IC) at Individual Time-points
Days 84/85, 3 h 55 min (n=146,145)
|
2.577 Liters
Standard Error 0.0332
|
2.439 Liters
Standard Error 0.0333
|
|
Inspiratory Capacity (IC) at Individual Time-points
Days 84/85, 23 h 40 min (n=153,150)
|
2.405 Liters
Standard Error 0.0371
|
2.337 Liters
Standard Error 0.0376
|
|
Inspiratory Capacity (IC) at Individual Time-points
Day 1, 3 h 55 min (n=160,173)
|
2.557 Liters
Standard Error 0.0298
|
2.475 Liters
Standard Error 0.0291
|
|
Inspiratory Capacity (IC) at Individual Time-points
Days 84/85, 20 min pre-dose (n=144,148)
|
2.444 Liters
Standard Error 0.0327
|
2.363 Liters
Standard Error 0.0324
|
SECONDARY outcome
Timeframe: Baseline, 12 weeksPopulation: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
The number of puffs of rescue medication taken in the previous 12 hours was recorded in the patient diary in the morning and evening. The total number of puffs of rescue medication per day over the whole active treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=219 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=216 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
|
-1.9 Number of puffs
Standard Error 0.16
|
-1.8 Number of puffs
Standard Error 0.16
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Dyspnea was measured at baseline using the Baseline Dyspnea Index (BDI) and during treatment using the Transitional Dyspnea Index (TDI). Analysis was done via mixed model. 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 is considered a minimal clinically important difference.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=207 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=209 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Transitional Dyspnea Index (TDI) Focal Score
|
2.506 Score
Standard Error 0.2781
|
2.012 Score
Standard Error 0.2797
|
SECONDARY outcome
Timeframe: Baseline, 12 weeksPopulation: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
The symptoms (respiratory, cough, wheeze, sputum color, sputum production, breathlessness, sore throat, nasal discharge or congestion, and fever) for the whole active treatment period was analyzed using a mixed model, which contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline symptom score, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilators as covariates and center nested in region as a random effect. Each symptom was scored as 0, 1, 2 or 3 where the description for each score varied. For each of the symptoms, the range of scores from 0 to 3 represented an increase in symptoms where 0 represented little to no symptom and 3 represented severe or worst symptom. The total symptom score, which is the sum of the individual scores, ranged from 0 (best possible outcome) to 27 (worst possible outcome).
Outcome measures
| Measure |
NVA237 + Indacaterol
n=212 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=214 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Cold symptom score
|
0.0 Score
Standard Error 0.02
|
0.0 Score
Standard Error 0.02
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Fever symptom score
|
0.0 Score
Standard Error 0.01
|
0.0 Score
Standard Error 0.01
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Sore throat symptom score
|
0.0 Score
Standard Error 0.01
|
0.0 Score
Standard Error 0.01
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Sputum color score
|
-0.1 Score
Standard Error 0.02
|
-0.1 Score
Standard Error 0.02
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Respiratory symptom score
|
-0.3 Score
Standard Error 0.03
|
-0.2 Score
Standard Error 0.03
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Cough symptom score
|
-0.2 Score
Standard Error 0.03
|
-0.2 Score
Standard Error 0.03
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Breathless symptom score
|
-0.2 Score
Standard Error 0.03
|
-0.2 Score
Standard Error 0.03
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Sputum production score
|
-0.1 Score
Standard Error 0.03
|
-0.1 Score
Standard Error 0.03
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Wheeze symptom score
|
-0.3 Score
Standard Error 0.03
|
-0.2 Score
Standard Error 0.03
|
|
Change From Baseline in Mean Daily Total and Individual Symptom Scores
Total symptom score
|
-1.2 Score
Standard Error 0.13
|
-1.1 Score
Standard Error 0.13
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Safety Set: The safety set included all patients who received at least one dose of study drug whether or not they were randomized.
All study emergent adverse events including Chronic Obstructive Pulmonary Disease exacerbations were monitored from screening through the end of study.
Outcome measures
| Measure |
NVA237 + Indacaterol
n=226 Participants
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=221 Participants
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Number of Participants With Adverse Events and Serious Adverse Events
Adverse Events (serious and non-serious)
|
85 Number of participants
|
75 Number of participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Serious adverse events
|
5 Number of participants
|
5 Number of participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Deaths
|
0 Number of participants
|
0 Number of participants
|
Adverse Events
NVA237 + Indacaterol
Placebo to NVA237 + Indacaterol
Serious adverse events
| Measure |
NVA237 + Indacaterol
n=226 participants at risk
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=221 participants at risk
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/226
|
0.45%
1/221
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.44%
1/226
|
0.00%
0/221
|
|
Immune system disorders
Hypersensitivity
|
0.44%
1/226
|
0.00%
0/221
|
|
Infections and infestations
Bacterial infection
|
0.44%
1/226
|
0.00%
0/221
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/226
|
0.45%
1/221
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/226
|
0.45%
1/221
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.44%
1/226
|
0.00%
0/221
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/226
|
0.45%
1/221
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.44%
1/226
|
0.90%
2/221
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.44%
1/226
|
0.00%
0/221
|
Other adverse events
| Measure |
NVA237 + Indacaterol
n=226 participants at risk
Participants received Indacaterol 150 ug once daily delivered via single dose dry powder inhaler (SDDPI) plus NVA237 50 ug once daily delivered via SDDPI
|
Placebo to NVA237 + Indacaterol
n=221 participants at risk
Participants received Indacaterol 150 ug once daily delivered via SDDPI plus placebo to NVA237 delivered via SDDPI
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
14.2%
32/226
|
12.2%
27/221
|
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