Trial Outcomes & Findings for NVA237 Versus Placebo 12-week Efficacy Study (NCT NCT01709864)
NCT ID: NCT01709864
Last Updated: 2015-03-04
Results Overview
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.
COMPLETED
PHASE3
440 participants
12 weeks
2015-03-04
Participant Flow
Participant milestones
| Measure |
NVA237
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
222
|
219
|
|
Overall Study
Full Analysis Set (FAS)
|
222
|
216
|
|
Overall Study
Per Protocol Set (PPS)
|
204
|
201
|
|
Overall Study
COMPLETED
|
215
|
208
|
|
Overall Study
NOT COMPLETED
|
7
|
11
|
Reasons for withdrawal
| Measure |
NVA237
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
subject/guardian decision
|
5
|
6
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
non-compliance with study treatment
|
1
|
1
|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
NVA237 Versus Placebo 12-week Efficacy Study
Baseline characteristics by cohort
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=219 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
Total
n=441 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.7 years
STANDARD_DEVIATION 8.36 • n=5 Participants
|
62.1 years
STANDARD_DEVIATION 8.34 • n=7 Participants
|
62.4 years
STANDARD_DEVIATION 8.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
98 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
185 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
124 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
256 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.
Outcome measures
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing
|
0.125 liters*hr
Standard Error 0.0162
|
-0.014 liters*hr
Standard Error 0.0165
|
SECONDARY outcome
Timeframe: Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.
Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose
Outcome measures
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Trough FEV1 Day 2 (n=218, n=214)
|
0.141 liters
Standard Error 0.0124
|
0.025 liters
Standard Error 0.0122
|
|
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Pre-dose Trough FEV1 Day 57 (n=217, n=208)
|
0.0106 liters
Standard Error 0.0156
|
-0.006 liters
Standard Error 0.0157
|
|
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Trough FEV1 Day 86 (n=218, n=214)
|
0.123 liters
Standard Error 0.0171
|
0.007 liters
Standard Error 0.0173
|
|
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Pre-dose Trough FEV1 Day 15 (n=217, n=208)
|
0.112 liters
Standard Error 0.0135
|
-0.002 liters
Standard Error 0.0135
|
|
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Pre-dose Trough FEV1 Day 29 (n=217, n=208)
|
0.0105 liters
Standard Error 0.0137
|
-0.005 liters
Standard Error 0.0136
|
|
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Pre-dose Trough FEV1 Day 85 (n=217, n=208)
|
0.090 liters
Standard Error 0.0155
|
-0.029 liters
Standard Error 0.0157
|
SECONDARY outcome
Timeframe: Day 1 and Week 12 (Day 85)Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.
Outcome measures
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 0-12h Day 1 (n=222, n=216)
|
0.140 liters*hr
Standard Error 0.0108
|
-0.001 liters*hr
Standard Error 0.0106
|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 0-4h Day 1 (n=222, n=216)
|
0.174 liters*hr
Standard Error 0.0103
|
0.021 liters*hr
Standard Error 0.0101
|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 0-4h Day 85 (n=222, n=216)
|
0.171 liters*hr
Standard Error 0.0163
|
0.001 liters*hr
Standard Error 0.0167
|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 4-8h Day 1 (n=222, n=215)
|
0.138 liters*hr
Standard Error 0.0123
|
0.001 liters*hr
Standard Error 0.0121
|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 4-8h Day 85 (n=222, n=215)
|
0.115 liters*hr
Standard Error 0.0172
|
-0.017 liters*hr
Standard Error 0.0174
|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 8-12h Day 1 (n=222, n=215)
|
0.102 liters*hr
Standard Error 0.0122
|
-0.037 liters*hr
Standard Error 0.0120
|
|
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
FEV1, AUC 8-12h Day 85 (n=222, n=215)
|
0.074 liters*hr
Standard Error 0.0166
|
-0.034 liters*hr
Standard Error 0.0168
|
SECONDARY outcome
Timeframe: Week 12Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).
Outcome measures
| Measure |
NVA237
n=210 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=192 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire
|
-4.4 score
Standard Error 0.96
|
-1.7 score
Standard Error 0.96
|
SECONDARY outcome
Timeframe: Week 12Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.
The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically significant improvement in SGRQ is defined as less than or equal to -4 change from baseline.
Outcome measures
| Measure |
NVA237
n=210 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=192 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12
|
49.0 percentage of participants
|
40.6 percentage of participants
|
SECONDARY outcome
Timeframe: Week 12Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.
Outcome measures
| Measure |
NVA237
n=200 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=188 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12
|
1.46 scores on a scale
Standard Error 0.289
|
0.54 scores on a scale
Standard Error 0.286
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.
Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least \& 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am \& pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day \& night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day \& night scores.
Outcome measures
| Measure |
NVA237
n=211 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=204 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline of Daily Symptom Scores
|
-1.39 Score
Standard Error 0.139
|
-1.01 Score
Standard Error 0.135
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only and included all randomized patients who received at least one dose of study drug.
Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am \& each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least \& 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day \& night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day \& night scores.
Outcome measures
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline of Morning and Nighttime Symptom Scores at Week 12
Daytime total symptom score (n=208,202)
|
-1.14 score
Standard Error 0.133
|
-0.73 score
Standard Error 0.130
|
|
Change From Baseline of Morning and Nighttime Symptom Scores at Week 12
nighttime total symptom score (n=207,202)
|
-1.22 score
Standard Error 0.143
|
-0.95 score
Standard Error 0.139
|
SECONDARY outcome
Timeframe: from Baseline up to 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Patients are reporting symptoms by using an electronic diary. A night with "no nighttime awakening" is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.
Outcome measures
| Measure |
NVA237
n=207 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=202 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Percentage of Nights With "no Nighttime Awakenings"
|
13.3 percentage of nights
Standard Error 2.00
|
11.3 percentage of nights
Standard Error 1.97
|
SECONDARY outcome
Timeframe: from Baseline up to 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Patients are reporting symptoms by using an electronic diary. A day with "no daytime symptoms" is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.
Outcome measures
| Measure |
NVA237
n=208 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=202 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Percentage of Days With "no Daytime Symptoms"
|
5.1 percentage of days
Standard Error 1.65
|
2.5 percentage of days
Standard Error 1.62
|
SECONDARY outcome
Timeframe: from Baseline up to 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization
Patients are reporting symptoms by using an electronic diary. A "day able to perform usual daily activities" is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.
Outcome measures
| Measure |
NVA237
n=208 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=202 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Percentage of "Days Able to Perform Usual Daily Activities"
|
8.6 pecentage of days
Standard Error 2.20
|
1.8 pecentage of days
Standard Error 2.15
|
SECONDARY outcome
Timeframe: baseline and 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period.
Outcome measures
| Measure |
NVA237
n=211 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=204 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
The Average Number of Puffs of Rescue Medication Per Day
|
-1.63 number of puffs
Standard Error 0.180
|
-0.86 number of puffs
Standard Error 0.177
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12
Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.
Outcome measures
| Measure |
NVA237
n=209 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=202 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Percentage of Days Without Rescue Medication Use
|
16.6 percentage of days
Standard Error 2.37
|
10.5 percentage of days
Standard Error 2.31
|
SECONDARY outcome
Timeframe: Baseline, Day 1 and Week 12 (Day 85)Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.
Outcome measures
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 2h (n=221, 216)
|
0.277 liters
Standard Error 0.0299
|
0.033 liters
Standard Error 0.0307
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 4h (n=220, 213)
|
0.215 liters
Standard Error 0.0317
|
0.076 liters
Standard Error 0.0321
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 11h 55min (n=216, 207)
|
0.110 liters
Standard Error 0.0286
|
-0.006 liters
Standard Error 0.0288
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 5 min (n=221, 214)
|
0.175 liters
Standard Error 0.0152
|
0.037 liters
Standard Error 0.0152
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 15 min (n=222, 216)
|
0.265 liters
Standard Error 0.0181
|
0.044 liters
Standard Error 0.0180
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 1h (n=222, 216)
|
0.318 liters
Standard Error 0.0207
|
0.032 liters
Standard Error 0.0205
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 2h (n=221, 216)
|
0.351 liters
Standard Error 0.0216
|
0.071 liters
Standard Error 0.0213
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 4h (n=220, 213)
|
0.290 liters
Standard Error 0.0235
|
0.067 liters
Standard Error 0.0231
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 6h (n=221, 214)
|
0.252 liters
Standard Error 0.0235
|
0.022 liters
Standard Error 0.0234
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 8h (n=220, 214)
|
0.192 liters
Standard Error 0.0221
|
-0.009 liters
Standard Error 0.0220
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 11h 55min (n=216, 207)
|
0.152 liters
Standard Error 0.0234
|
-0.030 liters
Standard Error 0.0235
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ -45 min (n=217, 208)
|
0.162 liters
Standard Error 0.0289
|
-0.043 liters
Standard Error 0.0296
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ -15 min (n=216, 208)
|
0.156 liters
Standard Error 0.0283
|
-0.017 liters
Standard Error 0.0287
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 5 min (n=221, 214)
|
0.184 liters
Standard Error 0.0282
|
-0.007 liters
Standard Error 0.0287
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 15 min (n=222, 216)
|
0.263 liters
Standard Error 0.0288
|
-0.003 liters
Standard Error 0.0294
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 1h (n=222, 216)
|
0.258 liters
Standard Error 0.0297
|
0.004 liters
Standard Error 0.0302
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 6h (n=221, 214)
|
0.199 liters
Standard Error 0.0304
|
-0.015 liters
Standard Error 0.0305
|
|
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 8h (n=220, 214)
|
0.128 liters
Standard Error 0.0303
|
-0.023 liters
Standard Error 0.0305
|
SECONDARY outcome
Timeframe: Baseline, Day 1 and Week 12 (Day 85)Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.
Outcome measures
| Measure |
NVA237
n=222 Participants
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 Participants
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 5 min (n=221, 214)
|
0.074 liters
Standard Error 0.0075
|
0.015 liters
Standard Error 0.0074
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 11h 55min (n=216, 207)
|
0.072 liters
Standard Error 0.0165
|
-0.043 liters
Standard Error 0.0165
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 15 min (n=222, 216)
|
0.129 liters
Standard Error 0.0085
|
0.015 liters
Standard Error 0.0084
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 1h (n=222, 216)
|
0.176 liters
Standard Error 0.0108
|
0.008 liters
Standard Error 0.0106
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 2h (n=221, 216)
|
0.198 liters
Standard Error 0.0120
|
0.031 liters
Standard Error 0.0118
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 4h (n=220, 213)
|
0.168 liters
Standard Error 0.0132
|
0.028 liters
Standard Error 0.0129
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 6h (n=221, 214)
|
0.132 liters
Standard Error 0.0135
|
0.000 liters
Standard Error 0.0134
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 8h (n=220, 214)
|
0.113 liters
Standard Error 0.0129
|
-0.022 liters
Standard Error 0.0128
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 1/ 11h 55min (n=216, 207)
|
0.083 liters
Standard Error 0.0131
|
-0.046 liters
Standard Error 0.0131
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ -45 min (n=217, 208)
|
0.092 liters
Standard Error 0.0154
|
-0.040 liters
Standard Error 0.0158
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ -15 min (n=216, 208)
|
0.090 liters
Standard Error 0.0160
|
-0.022 liters
Standard Error 0.0162
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 5 min (n=221, 214)
|
0.118 liters
Standard Error 0.0161
|
-0.018 liters
Standard Error 0.0163
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 15 min (n=222, 216)
|
0.171 liters
Standard Error 0.0164
|
-0.016 liters
Standard Error 0.0168
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 1h (n=222, 216)
|
0.178 liters
Standard Error 0.0166
|
-0.014 liters
Standard Error 0.0169
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 2h (n=221, 216)
|
0.186 liters
Standard Error 0.0178
|
0.006 liters
Standard Error 0.0183
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 4h (n=220, 213)
|
0.147 liters
Standard Error 0.0180
|
0.014 liters
Standard Error 0.0182
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 6h (n=221, 214)
|
0.120 liters
Standard Error 0.0183
|
-0.026 liters
Standard Error 0.0183
|
|
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
DAY 85/ 8h (n=220, 214)
|
0.080 liters
Standard Error 0.0180
|
-0.036 liters
Standard Error 0.0181
|
Adverse Events
NVA237
Placebo
Serious adverse events
| Measure |
NVA237
n=222 participants at risk
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 participants at risk
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
0.45%
1/222
|
0.00%
0/216
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.45%
1/222
|
0.46%
1/216
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/222
|
0.93%
2/216
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.90%
2/222
|
0.46%
1/216
|
|
Cardiac disorders
CARDIAC ARREST
|
0.00%
0/222
|
0.46%
1/216
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.00%
0/222
|
0.46%
1/216
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.00%
0/222
|
0.93%
2/216
|
|
Cardiac disorders
VENTRICULAR TACHYCARDIA
|
0.00%
0/222
|
0.46%
1/216
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.00%
0/222
|
0.46%
1/216
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.45%
1/222
|
0.00%
0/216
|
|
General disorders
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
|
0.45%
1/222
|
0.00%
0/216
|
|
Infections and infestations
BRONCHITIS
|
0.00%
0/222
|
0.46%
1/216
|
|
Infections and infestations
PNEUMONIA
|
0.45%
1/222
|
0.00%
0/216
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
0.00%
0/222
|
0.46%
1/216
|
|
Infections and infestations
WOUND INFECTION
|
0.00%
0/222
|
0.46%
1/216
|
|
Injury, poisoning and procedural complications
GUN SHOT WOUND
|
0.45%
1/222
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
HEAT STROKE
|
0.45%
1/222
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE
|
0.00%
0/222
|
0.46%
1/216
|
|
Investigations
VOLUME BLOOD DECREASED
|
0.00%
0/222
|
0.46%
1/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT
|
0.45%
1/222
|
0.00%
0/216
|
|
Nervous system disorders
SUBARACHNOID HAEMORRHAGE
|
0.00%
0/222
|
0.46%
1/216
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.45%
1/222
|
0.00%
0/216
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.00%
0/222
|
0.46%
1/216
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.90%
2/222
|
1.4%
3/216
|
Other adverse events
| Measure |
NVA237
n=222 participants at risk
NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
|
Placebo
n=216 participants at risk
Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
|
|---|---|---|
|
Ear and labyrinth disorders
VERTIGO
|
1.4%
3/222
|
0.00%
0/216
|
|
Eye disorders
VISION BLURRED
|
0.90%
2/222
|
0.46%
1/216
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/222
|
1.4%
3/216
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.90%
2/222
|
0.93%
2/216
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.45%
1/222
|
0.93%
2/216
|
|
Gastrointestinal disorders
NAUSEA
|
0.45%
1/222
|
0.93%
2/216
|
|
General disorders
FATIGUE
|
0.00%
0/222
|
0.93%
2/216
|
|
General disorders
OEDEMA PERIPHERAL
|
0.90%
2/222
|
0.93%
2/216
|
|
Infections and infestations
BRONCHITIS
|
1.4%
3/222
|
0.46%
1/216
|
|
Infections and infestations
GASTROENTERITIS VIRAL
|
0.00%
0/222
|
0.93%
2/216
|
|
Infections and infestations
INFLUENZA
|
0.90%
2/222
|
0.46%
1/216
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
1.4%
3/222
|
0.00%
0/216
|
|
Infections and infestations
NASOPHARYNGITIS
|
1.4%
3/222
|
3.2%
7/216
|
|
Infections and infestations
ORAL CANDIDIASIS
|
0.90%
2/222
|
0.46%
1/216
|
|
Infections and infestations
PNEUMONIA
|
1.4%
3/222
|
0.00%
0/216
|
|
Infections and infestations
SINUSITIS
|
1.4%
3/222
|
0.93%
2/216
|
|
Infections and infestations
TOOTH ABSCESS
|
0.00%
0/222
|
0.93%
2/216
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
3.6%
8/222
|
2.8%
6/216
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
0.90%
2/222
|
1.9%
4/216
|
|
Infections and infestations
URINARY TRACT INFECTION
|
1.4%
3/222
|
1.4%
3/216
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
0.90%
2/222
|
1.4%
3/216
|
|
Injury, poisoning and procedural complications
EXCORIATION
|
0.90%
2/222
|
0.00%
0/216
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/222
|
0.93%
2/216
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.45%
1/222
|
1.4%
3/216
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.90%
2/222
|
0.00%
0/216
|
|
Musculoskeletal and connective tissue disorders
ARTHROPATHY
|
0.00%
0/222
|
0.93%
2/216
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.90%
2/222
|
0.46%
1/216
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/222
|
0.93%
2/216
|
|
Nervous system disorders
HEADACHE
|
3.6%
8/222
|
2.8%
6/216
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.00%
0/222
|
0.93%
2/216
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
9.9%
22/222
|
12.0%
26/216
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
3.2%
7/222
|
2.3%
5/216
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/222
|
0.93%
2/216
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
1.8%
4/222
|
1.9%
4/216
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
1.8%
4/222
|
1.9%
4/216
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
0.00%
0/222
|
0.93%
2/216
|
|
Vascular disorders
HYPERTENSION
|
0.90%
2/222
|
0.00%
0/216
|
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