Trial Outcomes & Findings for Long Term Safety Study of NVA237 vs QAB149 in COPD Patients (NCT NCT01697696)
NCT ID: NCT01697696
Last Updated: 2016-03-16
Results Overview
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
COMPLETED
PHASE3
511 participants
52 weeks
2016-03-16
Participant Flow
Participant milestones
| Measure |
NVA237
12.5 μg twice-daily
|
QAB149
75 μg once-daily
|
|---|---|---|
|
Overall Study
STARTED
|
254
|
257
|
|
Overall Study
Safety Set
|
251
|
256
|
|
Overall Study
Full Analysis Set (FAS)
|
251
|
255
|
|
Overall Study
COMPLETED
|
207
|
210
|
|
Overall Study
NOT COMPLETED
|
47
|
47
|
Reasons for withdrawal
| Measure |
NVA237
12.5 μg twice-daily
|
QAB149
75 μg once-daily
|
|---|---|---|
|
Overall Study
Study terminated by sponsor
|
0
|
3
|
|
Overall Study
Protocol deviation
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Death
|
4
|
2
|
|
Overall Study
Lost to Follow-up
|
10
|
7
|
|
Overall Study
Subject/guardian decision
|
31
|
35
|
Baseline Characteristics
Long Term Safety Study of NVA237 vs QAB149 in COPD Patients
Baseline characteristics by cohort
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=256 Participants
75 μg once-daily
|
Total
n=507 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.3 Years
STANDARD_DEVIATION 9.15 • n=5 Participants
|
63.2 Years
STANDARD_DEVIATION 8.91 • n=7 Participants
|
63.3 Years
STANDARD_DEVIATION 9.02 • n=5 Participants
|
|
Sex: Female, Male
Female
|
110 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
217 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
141 Participants
n=5 Participants
|
149 Participants
n=7 Participants
|
290 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with safety assessments were included in this analysis
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Outcome measures
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=256 Participants
75 μg once-daily
|
|---|---|---|
|
Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate
|
77.3 Percentage of participants
|
77 Percentage of participants
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: The Safety set consisted of all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received.
Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems
Outcome measures
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=256 Participants
75 μg once-daily
|
|---|---|---|
|
Time to Treatment Discontinuation
|
NA Days
NA - Insufficient number of participants with events
|
388 Days
Interval 388.0 to
NA - Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: -45 min and -15 minutes baseline and at Week 52Population: The Full Analysis set (FAS) included patients who received at least one dose of study medication. Patients were analyzed according to the treatment to which they were randomized. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.
Outcome measures
| Measure |
NVA237
n=229 Participants
12.5 μg twice-daily
|
QAB149
n=227 Participants
75 μg once-daily
|
|---|---|---|
|
Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52
|
0.056 Liters
Standard Error 0.0211
|
0.060 Liters
Standard Error 0.0213
|
SECONDARY outcome
Timeframe: -45 min and -15 minutes baseline and at Week 52Population: The Full Analysis set (FAS). At each day/time point, only subjects with a value at both baseline and the respective day/time point are included. Only participants with baseline and specific post baseline time points 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.
Outcome measures
| Measure |
NVA237
n=229 Participants
12.5 μg twice-daily
|
QAB149
n=227 Participants
75 μg once-daily
|
|---|---|---|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 29/-45min
|
0.104 Liters
Standard Deviation 0.1848
|
0.118 Liters
Standard Deviation 0.2093
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 29/-15min
|
0.123 Liters
Standard Deviation 0.1872
|
0.138 Liters
Standard Deviation 0.2061
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 57/-45min
|
0.098 Liters
Standard Deviation 0.2017
|
0.101 Liters
Standard Deviation 0.2091
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 57/-15min
|
0.120 Liters
Standard Deviation 0.2025
|
0.107 Liters
Standard Deviation 0.2111
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 85/-45min
|
0.105 Liters
Standard Deviation 0.2410
|
0.085 Liters
Standard Deviation 0.2255
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 85/-15min
|
0.111 Liters
Standard Deviation 0.2137
|
0.099 Liters
Standard Deviation 0.2328
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 141/-45min
|
0.071 Liters
Standard Deviation 0.2168
|
0.089 Liters
Standard Deviation 0.2595
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 141/-15min
|
0.096 Liters
Standard Deviation 0.2060
|
0.108 Liters
Standard Deviation 0.2670
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 197/-45min
|
0.071 Liters
Standard Deviation 0.2370
|
0.082 Liters
Standard Deviation 0.2637
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 197/-15min
|
0.073 Liters
Standard Deviation 0.2150
|
0.090 Liters
Standard Deviation 0.2827
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 253/-45min
|
0.092 Liters
Standard Deviation 0.2774
|
0.087 Liters
Standard Deviation 0.2679
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 253/-15min
|
0.094 Liters
Standard Deviation 0.2100
|
0.103 Liters
Standard Deviation 0.2659
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 309/-45min
|
0.068 Liters
Standard Deviation 0.2850
|
0.094 Liters
Standard Deviation 0.2594
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 309/-15min
|
0.088 Liters
Standard Deviation 0.2845
|
0.112 Liters
Standard Deviation 0.2638
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 365/-45min
|
0.057 Liters
Standard Deviation 0.2541
|
0.088 Liters
Standard Deviation 0.2521
|
|
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Day 365/-15min
|
0.087 Liters
Standard Deviation 0.2592
|
0.090 Liters
Standard Deviation 0.2627
|
SECONDARY outcome
Timeframe: -45 min and -15 minutes baseline and at Week 52Population: Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants with baseline and specific post baseline time points 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.
Outcome measures
| Measure |
NVA237
n=229 Participants
12.5 μg twice-daily
|
QAB149
n=227 Participants
75 μg once-daily
|
|---|---|---|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 253/-15min
|
0.153 Liters
Standard Deviation 0.3703
|
0.125 Liters
Standard Deviation 0.3984
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 29/-45min
|
0.191 Liters
Standard Deviation 0.3433
|
0.170 Liters
Standard Deviation 0.3536
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 29/-15min
|
0.217 Liters
Standard Deviation 0.3440
|
0.194 Liters
Standard Deviation 0.3495
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 57/-45min
|
0.168 Liters
Standard Deviation 0.3501
|
0.140 Liters
Standard Deviation 0.3655
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 57/-15min
|
0.210 Liters
Standard Deviation 0.3414
|
0.178 Liters
Standard Deviation 0.3610
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 85/-45min
|
0.171 Liters
Standard Deviation 0.3907
|
0.094 Liters
Standard Deviation 0.3711
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 85/-15min
|
0.188 Liters
Standard Deviation 0.3875
|
0.118 Liters
Standard Deviation 0.3823
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 141/-45min
|
0.159 Liters
Standard Deviation 0.3742
|
0.112 Liters
Standard Deviation 0.3822
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 141/-15min
|
0.182 Liters
Standard Deviation 0.3706
|
0.141 Liters
Standard Deviation 0.4068
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 197/-45min
|
0.140 Liters
Standard Deviation 0.3879
|
0.075 Liters
Standard Deviation 0.4043
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 197/-15min
|
0.133 Liters
Standard Deviation 0.3992
|
0.083 Liters
Standard Deviation 0.4183
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 253/-45min
|
0.167 Liters
Standard Deviation 0.4567
|
0.100 Liters
Standard Deviation 0.4219
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 309/-45min
|
0.120 Liters
Standard Deviation 0.4539
|
0.094 Liters
Standard Deviation 0.4122
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 309/-15min
|
0.149 Liters
Standard Deviation 0.4451
|
0.114 Liters
Standard Deviation 0.4207
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 365/-45min
|
0.116 Liters
Standard Deviation 0.4053
|
0.109 Liters
Standard Deviation 0.4426
|
|
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Day 365/-15min
|
0.143 Liters
Standard Deviation 0.3970
|
0.097 Liters
Standard Deviation 0.4171
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. 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 total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18.
Outcome measures
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=255 Participants
75 μg once-daily
|
|---|---|---|
|
Change From Baseline in COPD Symptoms
Daily total symptom score (n=231, 227)
|
-1.18 scores on a scale
Standard Error 0.137
|
-1.47 scores on a scale
Standard Error 0.137
|
|
Change From Baseline in COPD Symptoms
Daytime total symptom score (n=221, 220)
|
-0.95 scores on a scale
Standard Error 0.129
|
-1.14 scores on a scale
Standard Error 0.129
|
|
Change From Baseline in COPD Symptoms
Nighttime total symptom score (n=226, 222)
|
-1.11 scores on a scale
Standard Error 0.126
|
-1.25 scores on a scale
Standard Error 0.128
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.
Outcome measures
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=255 Participants
75 μg once-daily
|
|---|---|---|
|
Change From Baseline in COPD Symptoms
Nights with no nighttime awakenings (n=226, 222)
|
17.4 Percentage of days / nights
Standard Error 1.84
|
18.0 Percentage of days / nights
Standard Error 1.86
|
|
Change From Baseline in COPD Symptoms
Days with no daytime symptoms (n=221, 220)
|
6.0 Percentage of days / nights
Standard Error 1.38
|
5.1 Percentage of days / nights
Standard Error 1.38
|
|
Change From Baseline in COPD Symptoms
Days able to perform daily activities(n=221,220)
|
5.4 Percentage of days / nights
Standard Error 2.09
|
8.5 Percentage of days / nights
Standard Error 2.10
|
SECONDARY outcome
Timeframe: 52 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 by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week 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. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect
Outcome measures
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=255 Participants
75 μg once-daily
|
|---|---|---|
|
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
Daily (n=231, 227)
|
-1.16 Number of puffs
Standard Error 0.199
|
-1.79 Number of puffs
Standard Error 0.199
|
|
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
Daytime (n=221, 220)
|
-0.71 Number of puffs
Standard Error 0.112
|
-1.05 Number of puffs
Standard Error 0.112
|
|
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
Nighttime (n=226, 222)
|
-0.52 Number of puffs
Standard Error 0.094
|
-0.73 Number of puffs
Standard Error 0.095
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Patients were analyzed according to the treatment to which they were randomized
COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.
Outcome measures
| Measure |
NVA237
n=251 Participants
12.5 μg twice-daily
|
QAB149
n=255 Participants
75 μg once-daily
|
|---|---|---|
|
Time to First COPD Exacerbation (Moderate or Severe).
|
NA Days
NA - Insufficient number of participants with events
|
NA Days
NA - Insufficient number of participants with events
|
Adverse Events
NVA237
QAB149
Serious adverse events
| Measure |
NVA237
n=251 participants at risk
12.5 μg twice-daily
|
QAB149
n=256 participants at risk
75 μg once-daily
|
|---|---|---|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.40%
1/251
|
0.78%
2/256
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.40%
1/251
|
0.00%
0/256
|
|
Cardiac disorders
ARTERIOSCLEROSIS CORONARY ARTERY
|
0.00%
0/251
|
0.39%
1/256
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.80%
2/251
|
0.39%
1/256
|
|
Cardiac disorders
CARDIAC ARREST
|
0.00%
0/251
|
0.78%
2/256
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.00%
0/251
|
0.39%
1/256
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.40%
1/251
|
0.39%
1/256
|
|
Cardiac disorders
CORONARY ARTERY STENOSIS
|
0.40%
1/251
|
0.39%
1/256
|
|
Cardiac disorders
HYPERTENSIVE HEART DISEASE
|
0.40%
1/251
|
0.00%
0/256
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.40%
1/251
|
0.39%
1/256
|
|
Cardiac disorders
STRESS CARDIOMYOPATHY
|
0.00%
0/251
|
0.39%
1/256
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
0.40%
1/251
|
0.00%
0/256
|
|
Cardiac disorders
VENTRICULAR FIBRILLATION
|
0.00%
0/251
|
0.39%
1/256
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/251
|
0.39%
1/256
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.40%
1/251
|
0.39%
1/256
|
|
Gastrointestinal disorders
INCARCERATED UMBILICAL HERNIA
|
0.40%
1/251
|
0.00%
0/256
|
|
Gastrointestinal disorders
LARGE INTESTINE POLYP
|
0.40%
1/251
|
0.00%
0/256
|
|
Gastrointestinal disorders
SMALL INTESTINAL OBSTRUCTION
|
0.40%
1/251
|
0.00%
0/256
|
|
Gastrointestinal disorders
SWOLLEN TONGUE
|
0.00%
0/251
|
0.39%
1/256
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.80%
2/251
|
0.00%
0/256
|
|
Hepatobiliary disorders
CHOLECYSTITIS CHRONIC
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
ABSCESS LIMB
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
ACUTE SINUSITIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
APPENDICITIS
|
0.40%
1/251
|
0.00%
0/256
|
|
Infections and infestations
BRONCHITIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
DIVERTICULITIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
|
0.40%
1/251
|
0.00%
0/256
|
|
Infections and infestations
INFLUENZA
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
LOBAR PNEUMONIA
|
0.40%
1/251
|
0.00%
0/256
|
|
Infections and infestations
PNEUMONIA
|
2.0%
5/251
|
1.6%
4/256
|
|
Infections and infestations
SEPSIS
|
0.00%
0/251
|
0.78%
2/256
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/251
|
0.39%
1/256
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
0.40%
1/251
|
0.00%
0/256
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/251
|
0.39%
1/256
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.40%
1/251
|
0.00%
0/256
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.00%
0/251
|
0.39%
1/256
|
|
Injury, poisoning and procedural complications
JOINT INJURY
|
0.00%
0/251
|
0.39%
1/256
|
|
Injury, poisoning and procedural complications
POST-TRAUMATIC PAIN
|
0.00%
0/251
|
0.39%
1/256
|
|
Injury, poisoning and procedural complications
RADIATION OESOPHAGITIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Injury, poisoning and procedural complications
RIB FRACTURE
|
0.00%
0/251
|
0.39%
1/256
|
|
Injury, poisoning and procedural complications
SPINAL COMPRESSION FRACTURE
|
0.00%
0/251
|
0.39%
1/256
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/251
|
0.39%
1/256
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/251
|
0.39%
1/256
|
|
Investigations
LIVER FUNCTION TEST ABNORMAL
|
0.00%
0/251
|
0.39%
1/256
|
|
Metabolism and nutrition disorders
FLUID OVERLOAD
|
0.40%
1/251
|
0.00%
0/256
|
|
Metabolism and nutrition disorders
HYPERAMMONAEMIA
|
0.00%
0/251
|
0.39%
1/256
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
0.00%
0/251
|
0.39%
1/256
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/251
|
0.78%
2/256
|
|
Musculoskeletal and connective tissue disorders
JOINT SWELLING
|
0.00%
0/251
|
0.39%
1/256
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.40%
1/251
|
0.00%
0/256
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER CANCER
|
0.40%
1/251
|
0.00%
0/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
GLIOBLASTOMA MULTIFORME
|
0.00%
0/251
|
0.39%
1/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INVASIVE DUCTAL BREAST CARCINOMA
|
0.40%
1/251
|
0.39%
1/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT
|
0.00%
0/251
|
0.39%
1/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OESOPHAGEAL CARCINOMA
|
0.40%
1/251
|
0.00%
0/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.00%
0/251
|
0.39%
1/256
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SMALL CELL LUNG CANCER
|
0.00%
0/251
|
0.39%
1/256
|
|
Nervous system disorders
CAROTID ARTERY STENOSIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Nervous system disorders
CEREBRAL THROMBOSIS
|
0.40%
1/251
|
0.00%
0/256
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.40%
1/251
|
0.00%
0/256
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/251
|
0.39%
1/256
|
|
Nervous system disorders
DYSARTHRIA
|
0.00%
0/251
|
0.39%
1/256
|
|
Nervous system disorders
GENERALISED TONIC-CLONIC SEIZURE
|
0.40%
1/251
|
0.00%
0/256
|
|
Nervous system disorders
PARTIAL SEIZURES
|
0.00%
0/251
|
0.39%
1/256
|
|
Nervous system disorders
SYNCOPE
|
0.00%
0/251
|
0.39%
1/256
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.40%
1/251
|
0.00%
0/256
|
|
Psychiatric disorders
ALCOHOL ABUSE
|
0.00%
0/251
|
0.39%
1/256
|
|
Psychiatric disorders
ALCOHOLISM
|
0.00%
0/251
|
0.39%
1/256
|
|
Psychiatric disorders
BIPOLAR DISORDER
|
0.00%
0/251
|
0.39%
1/256
|
|
Psychiatric disorders
DYSPHORIA
|
0.00%
0/251
|
0.39%
1/256
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
0.40%
1/251
|
0.00%
0/256
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/251
|
0.39%
1/256
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.40%
1/251
|
0.39%
1/256
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.80%
2/251
|
0.78%
2/256
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
4.4%
11/251
|
4.7%
12/256
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC RESPIRATORY FAILURE
|
0.40%
1/251
|
0.00%
0/256
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.40%
1/251
|
0.00%
0/256
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
0.40%
1/251
|
0.00%
0/256
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY ARREST
|
0.40%
1/251
|
0.00%
0/256
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
1.2%
3/251
|
0.00%
0/256
|
|
Respiratory, thoracic and mediastinal disorders
SLEEP APNOEA SYNDROME
|
0.00%
0/251
|
0.39%
1/256
|
|
Skin and subcutaneous tissue disorders
SKIN REACTION
|
0.00%
0/251
|
0.39%
1/256
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
0.00%
0/251
|
0.39%
1/256
|
|
Vascular disorders
AORTIC DISSECTION
|
0.00%
0/251
|
0.39%
1/256
|
|
Vascular disorders
ARTERIOSCLEROSIS
|
0.40%
1/251
|
0.00%
0/256
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
0.40%
1/251
|
0.00%
0/256
|
Other adverse events
| Measure |
NVA237
n=251 participants at risk
12.5 μg twice-daily
|
QAB149
n=256 participants at risk
75 μg once-daily
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/251
|
2.0%
5/256
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.40%
1/251
|
1.2%
3/256
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
1.2%
3/251
|
0.00%
0/256
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
2.8%
7/251
|
0.00%
0/256
|
|
Gastrointestinal disorders
CONSTIPATION
|
1.6%
4/251
|
0.78%
2/256
|
|
Gastrointestinal disorders
DENTAL CARIES
|
0.00%
0/251
|
1.2%
3/256
|
|
Gastrointestinal disorders
DIARRHOEA
|
3.6%
9/251
|
2.0%
5/256
|
|
Gastrointestinal disorders
DRY MOUTH
|
1.2%
3/251
|
0.00%
0/256
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
1.6%
4/251
|
1.2%
3/256
|
|
Gastrointestinal disorders
NAUSEA
|
3.6%
9/251
|
2.3%
6/256
|
|
Gastrointestinal disorders
TOOTHACHE
|
1.2%
3/251
|
1.6%
4/256
|
|
Gastrointestinal disorders
VOMITING
|
2.0%
5/251
|
2.7%
7/256
|
|
General disorders
FATIGUE
|
4.4%
11/251
|
1.2%
3/256
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.40%
1/251
|
1.2%
3/256
|
|
General disorders
OEDEMA PERIPHERAL
|
0.80%
2/251
|
2.3%
6/256
|
|
Immune system disorders
SEASONAL ALLERGY
|
0.40%
1/251
|
1.2%
3/256
|
|
Infections and infestations
BRONCHITIS
|
4.4%
11/251
|
3.5%
9/256
|
|
Infections and infestations
DIVERTICULITIS
|
0.80%
2/251
|
1.2%
3/256
|
|
Infections and infestations
GASTROENTERITIS VIRAL
|
1.2%
3/251
|
0.78%
2/256
|
|
Infections and infestations
INFLUENZA
|
2.8%
7/251
|
1.2%
3/256
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
1.2%
3/251
|
3.9%
10/256
|
|
Infections and infestations
NASOPHARYNGITIS
|
8.0%
20/251
|
10.5%
27/256
|
|
Infections and infestations
ORAL CANDIDIASIS
|
0.40%
1/251
|
2.0%
5/256
|
|
Infections and infestations
RHINITIS
|
2.0%
5/251
|
0.39%
1/256
|
|
Infections and infestations
SINUSITIS
|
4.0%
10/251
|
4.7%
12/256
|
|
Infections and infestations
TOOTH ABSCESS
|
1.2%
3/251
|
0.39%
1/256
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
5.6%
14/251
|
6.2%
16/256
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
4.0%
10/251
|
2.0%
5/256
|
|
Infections and infestations
URINARY TRACT INFECTION
|
3.2%
8/251
|
2.0%
5/256
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
4.8%
12/251
|
4.7%
12/256
|
|
Injury, poisoning and procedural complications
ARTHROPOD BITE
|
1.6%
4/251
|
0.78%
2/256
|
|
Injury, poisoning and procedural complications
CONTUSION
|
1.6%
4/251
|
0.00%
0/256
|
|
Injury, poisoning and procedural complications
FALL
|
2.0%
5/251
|
1.2%
3/256
|
|
Injury, poisoning and procedural complications
MUSCLE STRAIN
|
1.2%
3/251
|
1.6%
4/256
|
|
Injury, poisoning and procedural complications
PROCEDURAL PAIN
|
0.40%
1/251
|
1.6%
4/256
|
|
Investigations
BLOOD PRESSURE INCREASED
|
1.6%
4/251
|
0.39%
1/256
|
|
Investigations
WEIGHT DECREASED
|
1.2%
3/251
|
0.78%
2/256
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
1.2%
3/251
|
0.78%
2/256
|
|
Metabolism and nutrition disorders
HYPERLIPIDAEMIA
|
1.2%
3/251
|
0.39%
1/256
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.40%
1/251
|
1.2%
3/256
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
2.8%
7/251
|
2.3%
6/256
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
3.2%
8/251
|
1.6%
4/256
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
1.2%
3/251
|
2.3%
6/256
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
1.2%
3/251
|
1.6%
4/256
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.40%
1/251
|
1.2%
3/256
|
|
Musculoskeletal and connective tissue disorders
TENOSYNOVITIS STENOSANS
|
1.2%
3/251
|
0.00%
0/256
|
|
Nervous system disorders
DIZZINESS
|
2.0%
5/251
|
2.3%
6/256
|
|
Nervous system disorders
HEADACHE
|
1.6%
4/251
|
3.1%
8/256
|
|
Nervous system disorders
SYNCOPE
|
1.6%
4/251
|
0.39%
1/256
|
|
Nervous system disorders
TREMOR
|
1.6%
4/251
|
0.78%
2/256
|
|
Psychiatric disorders
ANXIETY
|
1.6%
4/251
|
2.7%
7/256
|
|
Psychiatric disorders
DEPRESSION
|
1.2%
3/251
|
1.6%
4/256
|
|
Psychiatric disorders
INSOMNIA
|
1.6%
4/251
|
0.78%
2/256
|
|
Renal and urinary disorders
HAEMATURIA
|
0.00%
0/251
|
1.6%
4/256
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
33.1%
83/251
|
34.4%
88/256
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
7.2%
18/251
|
7.8%
20/256
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
5.2%
13/251
|
3.5%
9/256
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
0.40%
1/251
|
1.2%
3/256
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
3.6%
9/251
|
3.5%
9/256
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
4.4%
11/251
|
4.3%
11/256
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
0.80%
2/251
|
1.2%
3/256
|
|
Respiratory, thoracic and mediastinal disorders
RHINITIS ALLERGIC
|
1.2%
3/251
|
1.2%
3/256
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
1.6%
4/251
|
2.0%
5/256
|
|
Respiratory, thoracic and mediastinal disorders
SINUS CONGESTION
|
1.6%
4/251
|
2.3%
6/256
|
|
Respiratory, thoracic and mediastinal disorders
SPUTUM INCREASED
|
1.2%
3/251
|
0.39%
1/256
|
|
Respiratory, thoracic and mediastinal disorders
WHEEZING
|
2.0%
5/251
|
0.39%
1/256
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.00%
0/251
|
1.2%
3/256
|
|
Vascular disorders
HYPERTENSION
|
1.2%
3/251
|
3.1%
8/256
|
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