Trial Outcomes & Findings for Efficacy of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01922271)
NCT ID: NCT01922271
Last Updated: 2015-01-01
Results Overview
Standardized Forced Expiratory Volume in One Second (FEV1) AUC0-2h will be measured via spirometry. The AUC will be calculated from the FEV1 measurements obtained at timepoints between 0 min and 2h using the trapezoidal rule and will be standardized (=divided) by the measurement time (i.e. 2h).
COMPLETED
PHASE4
152 participants
Day 1
2015-01-01
Participant Flow
Participant milestones
| Measure |
NVA237 Followed by Tiotropium
Period 1: NVA237 plus placebo to tiotropium on day 1, followed by a 7 day washout. Period 2: tiotropium plus placebo to NVA237 on day 8. Salbutamol was used as rescue medication.
|
Tiotropium Followed by NVA237
Period 1: tiotropium plus placebo to NVA237 on day 1, followed by a 7 day washout. Period 2: NVA237 plus placebo to tiotropium on day 8. Salbutamol was used as rescue medication.
|
|---|---|---|
|
PERIOD 1
STARTED
|
76
|
76
|
|
PERIOD 1
COMPLETED
|
76
|
76
|
|
PERIOD 1
NOT COMPLETED
|
0
|
0
|
|
WASHOUT Period
STARTED
|
76
|
76
|
|
WASHOUT Period
COMPLETED
|
75
|
76
|
|
WASHOUT Period
NOT COMPLETED
|
1
|
0
|
|
PERIOD 2
STARTED
|
75
|
76
|
|
PERIOD 2
COMPLETED
|
75
|
76
|
|
PERIOD 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
NVA237 Followed by Tiotropium
Period 1: NVA237 plus placebo to tiotropium on day 1, followed by a 7 day washout. Period 2: tiotropium plus placebo to NVA237 on day 8. Salbutamol was used as rescue medication.
|
Tiotropium Followed by NVA237
Period 1: tiotropium plus placebo to NVA237 on day 1, followed by a 7 day washout. Period 2: NVA237 plus placebo to tiotropium on day 8. Salbutamol was used as rescue medication.
|
|---|---|---|
|
WASHOUT Period
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Efficacy of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
NVA237 Followed by Tiotropium
n=76 Participants
Period 1: NVA237 plus placebo to tiotropium on day 1, followed by a 7 day washout. Period 2: tiotropium plus placebo to NVA237 on day 8. Salbutamol was used as rescue medication.
|
Tiotropium Followed by NVA237
n=76 Participants
Period 1: tiotropium plus placebo to NVA237 on day 1, followed by a 7 day washout. Period 2: NVA237 plus placebo to tiotropium on day 8. Salbutamol was used as rescue medication.
|
Total
n=152 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.9 years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
61.7 years
STANDARD_DEVIATION 8.2 • n=7 Participants
|
61.8 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
98 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Standardized Forced Expiratory Volume in One Second (FEV1) AUC0-2h will be measured via spirometry. The AUC will be calculated from the FEV1 measurements obtained at timepoints between 0 min and 2h using the trapezoidal rule and will be standardized (=divided) by the measurement time (i.e. 2h).
Outcome measures
| Measure |
NVA237
n=151 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=150 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-2
|
1.490 liters per hour
Standard Deviation 0.4232
|
1.453 liters per hour
Standard Deviation 0.4135
|
SECONDARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 will be measured by spirometry. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.
Outcome measures
| Measure |
NVA237
n=152 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=151 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Forced Expiratory Volume in One Second (FEV1) 15 Min Post Dose
|
1.433 liters per hour
Standard Deviation 0.4110
|
1.398 liters per hour
Standard Deviation 0.4092
|
SECONDARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Specific Airway Resistance (sRAW) indicates volume and resistance-dependent work of breathing needed in order to generate a reference flow rate of 1 L/s, measured by kPa\*s. Whole body plethysmography (Bodybox) is used to measure SRaw.
Outcome measures
| Measure |
NVA237
n=152 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=152 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Specific Airway Resistance (sRAW)
-45 min (n=152, 150)
|
4.203 kilopascal (kPa)
Standard Deviation 1.8102
|
4.105 kilopascal (kPa)
Standard Deviation 1.8338
|
|
Specific Airway Resistance (sRAW)
30 min (n=150, 151)
|
2.904 kilopascal (kPa)
Standard Deviation 1.4759
|
3.089 kilopascal (kPa)
Standard Deviation 1.4555
|
|
Specific Airway Resistance (sRAW)
1 hr (n=151, 149)
|
2.656 kilopascal (kPa)
Standard Deviation 1.3062
|
2.877 kilopascal (kPa)
Standard Deviation 1.4130
|
|
Specific Airway Resistance (sRAW)
1 hr 30 min (n=151, 150)
|
2.632 kilopascal (kPa)
Standard Deviation 1.3152
|
2.811 kilopascal (kPa)
Standard Deviation 1.4065
|
|
Specific Airway Resistance (sRAW)
2 hr 30 min (n=150, 149)
|
2.643 kilopascal (kPa)
Standard Deviation 1.3146
|
2.756 kilopascal (kPa)
Standard Deviation 1.4091
|
|
Specific Airway Resistance (sRAW)
3 hr 30 min (n=150, 149)
|
2.779 kilopascal (kPa)
Standard Deviation 1.4496
|
2.828 kilopascal (kPa)
Standard Deviation 1.4534
|
SECONDARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Functional Resistance Capacity (FRCpleth) will be measured using whole body plethysmography (Bodybox).
Outcome measures
| Measure |
NVA237
n=152 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=152 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Functional Resistance Capacity (FRCpleth)
-45 min (n=152, 150)
|
5.211 Liters
Standard Deviation 1.3086
|
5.142 Liters
Standard Deviation 1.2656
|
|
Functional Resistance Capacity (FRCpleth)
30 min (n=150, 151)
|
4.823 Liters
Standard Deviation 1.2517
|
4.852 Liters
Standard Deviation 1.1812
|
|
Functional Resistance Capacity (FRCpleth)
1 hr (n=151, 149)
|
4.769 Liters
Standard Deviation 1.2571
|
4.725 Liters
Standard Deviation 1.1496
|
|
Functional Resistance Capacity (FRCpleth)
1 hr 30 min (n=151, 149)
|
4.756 Liters
Standard Deviation 1.2366
|
4.714 Liters
Standard Deviation 1.1523
|
|
Functional Resistance Capacity (FRCpleth)
2 h 30 min (n= 150, 149)
|
4.736 Liters
Standard Deviation 1.1545
|
4.676 Liters
Standard Deviation 1.2243
|
|
Functional Resistance Capacity (FRCpleth)
3 h 30 min (n= 150, 148)
|
4.761 Liters
Standard Deviation 1.2286
|
4.704 Liters
Standard Deviation 1.1911
|
SECONDARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Residual Volume (RV) will be measured using whole body plethysmography (Bodybox).
Outcome measures
| Measure |
NVA237
n=152 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=152 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Residual Volume (RV)
-45 min (n=152, 150)
|
4.433 Liters
Standard Deviation 1.2596
|
4.344 Liters
Standard Deviation 1.1707
|
|
Residual Volume (RV)
30 min (n=150, 151)
|
3.996 Liters
Standard Deviation 1.1862
|
4.035 Liters
Standard Deviation 1.0689
|
|
Residual Volume (RV)
1 hr (n=151, 149)
|
3.891 Liters
Standard Deviation 1.1997
|
3.913 Liters
Standard Deviation 1.0281
|
|
Residual Volume (RV)
1 hr 30 min (n=151, 149)
|
3.910 Liters
Standard Deviation 1.1534
|
3.903 Liters
Standard Deviation 1.0281
|
|
Residual Volume (RV)
2 h 30 min (n= 150, 149)
|
3.893 Liters
Standard Deviation 1.0486
|
3.861 Liters
Standard Deviation 1.1058
|
|
Residual Volume (RV)
3 h 30 min (n= 150, 148)
|
3.970 Liters
Standard Deviation 1.1576
|
3.895 Liters
Standard Deviation 1.0740
|
SECONDARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Total Lung Capacity (TLC) is the best vital capacity plus residual volume (RV). Whole body plethysmography (Bodybox) will be used to measure TLC.
Outcome measures
| Measure |
NVA237
n=152 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=152 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Total Lung Capacity (TLC)
-45 min (n=152, 150)
|
7.380 Liters
Standard Deviation 1.4781
|
7.335 Liters
Standard Deviation 1.4328
|
|
Total Lung Capacity (TLC)
30 min (n=150, 151)
|
7.255 Liters
Standard Deviation 1.4628
|
7.274 Liters
Standard Deviation 1.4032
|
|
Total Lung Capacity (TLC)
1hr (n=151, 149)
|
7.224 Liters
Standard Deviation 1.4294
|
7.161 Liters
Standard Deviation 1.4015
|
|
Total Lung Capacity (TLC)
1hr 30 min (n=151, 149)
|
7.227 Liters
Standard Deviation 1.4383
|
7.165 Liters
Standard Deviation 1.3690
|
|
Total Lung Capacity (TLC)
2hr 30 min (n=150, 149)
|
7.203 Liters
Standard Deviation 1.3700
|
7.149 Liters
Standard Deviation 1.4476
|
|
Total Lung Capacity (TLC)
3hr 30 min (n=150, 148)
|
7.240 Liters
Standard Deviation 1.4297
|
7.149 Liters
Standard Deviation 1.3963
|
SECONDARY outcome
Timeframe: Day 1Population: The Full Analysis Set (FAS) consisted of all randomized patients who applied at least one dose of study medication during at least one study period.
Inspiratory Capacity (IC) is the volume of air breathed in by a maximum inspiration at the end of a normal expiration. Whole body plethysmography (Bodybox) will be used to measure IC.
Outcome measures
| Measure |
NVA237
n=152 Participants
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=152 Participants
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Inspiratory Capacity (IC)
1hr (n=151, 149)
|
2.455 Liters
Standard Deviation 0.6001
|
2.435 Liters
Standard Deviation 0.5908
|
|
Inspiratory Capacity (IC)
-45 min (n=152, 150)
|
2.169 Liters
Standard Deviation 0.5548
|
2.193 Liters
Standard Deviation 0.5583
|
|
Inspiratory Capacity (IC)
30 min (n=150, 151)
|
2.433 Liters
Standard Deviation 0.5934
|
2.422 Liters
Standard Deviation 0.5996
|
|
Inspiratory Capacity (IC)
1hr 30 min (n=151, 150)
|
2.472 Liters
Standard Deviation 0.6200
|
2.457 Liters
Standard Deviation 0.5883
|
|
Inspiratory Capacity (IC)
2hr 30 min (n=150, 149)
|
2.467 Liters
Standard Deviation 0.5929
|
2.474 Liters
Standard Deviation 0.6051
|
|
Inspiratory Capacity (IC)
3hr 30 min (n=150, 149)
|
2.479 Liters
Standard Deviation 0.6036
|
2.449 Liters
Standard Deviation 0.5907
|
Adverse Events
NVA237
Tiotropium
Serious adverse events
| Measure |
NVA237
n=152 participants at risk
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=151 participants at risk
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.66%
1/152
|
0.00%
0/151
|
|
Cardiac disorders
Myocardial infarction
|
0.66%
1/152
|
0.00%
0/151
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/152
|
0.66%
1/151
|
|
Surgical and medical procedures
Nephrectomy
|
0.00%
0/152
|
0.66%
1/151
|
Other adverse events
| Measure |
NVA237
n=152 participants at risk
ALL patients on NVA237 for Period 1 \& Period 2
|
Tiotropium
n=151 participants at risk
ALL patients onTiotropium for Period 1 \& Period 2
|
|---|---|---|
|
General disorders
Condition aggravated
|
0.66%
1/152
|
0.00%
0/151
|
|
Infections and infestations
Nasopharyngitis
|
2.0%
3/152
|
2.6%
4/151
|
|
Infections and infestations
Rhinitis
|
0.00%
0/152
|
1.3%
2/151
|
|
Infections and infestations
Urinary tract infection
|
0.66%
1/152
|
0.00%
0/151
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/152
|
0.66%
1/151
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.66%
1/152
|
0.00%
0/151
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/152
|
0.66%
1/151
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.66%
1/152
|
0.00%
0/151
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/152
|
0.66%
1/151
|
|
Nervous system disorders
Headache
|
0.66%
1/152
|
0.66%
1/151
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/152
|
0.66%
1/151
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.66%
1/152
|
1.3%
2/151
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.66%
1/152
|
2.0%
3/151
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
2/152
|
0.00%
0/151
|
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