Trial Outcomes & Findings for Efficacy and Safety of Four Doses of Glycopyrronium Bromide (NVA237) in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD), in Comparison to an Active Comparator Tiotropium (NCT NCT00501852)
NCT ID: NCT00501852
Last Updated: 2012-05-08
Results Overview
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
83 participants
Primary outcome timeframe
Day 7
Results posted on
2012-05-08
Participant Flow
Participant milestones
| Measure |
Overall Study
|
|---|---|
|
Overall Study
STARTED
|
83
|
|
Overall Study
NVA237 12.5µg
|
55
|
|
Overall Study
NVA237 25µg
|
51
|
|
Overall Study
NVA237 50µg
|
53
|
|
Overall Study
NVA237 100µg
|
54
|
|
Overall Study
Placebo
|
55
|
|
Overall Study
Tiotropium
|
55
|
|
Overall Study
COMPLETED
|
78
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Overall Study
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
Efficacy and Safety of Four Doses of Glycopyrronium Bromide (NVA237) in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD), in Comparison to an Active Comparator Tiotropium
Baseline characteristics by cohort
| Measure |
Overall Study
n=83 Participants
|
|---|---|
|
Age Continuous
|
64.4 years
STANDARD_DEVIATION 9.05 • n=113 Participants
|
|
Age, Customized
40-64 years
|
39 participants
n=113 Participants
|
|
Age, Customized
>= 65 years
|
44 participants
n=113 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=113 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=113 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=113 Participants
|
|
Race (NIH/OMB)
Asian
|
25 Participants
n=113 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=113 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=113 Participants
|
|
Race (NIH/OMB)
White
|
58 Participants
n=113 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=113 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=113 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: Modified Intent-to-Treat (mITT) population. The modified intent-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients were analyzed according to the treatment they received.
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing.
Outcome measures
| Measure |
NVA237 12.5 ug
n=55 Participants
12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 25 ug
n=51 Participants
25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 50 ug
n=53 Participants
50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 100 ug
n=53 Participants
100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Placebo
n=49 Participants
Placebo via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Tiotropium Bromide
n=55 Participants
18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
|---|---|---|---|---|---|---|
|
Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment
|
1.317 Liters
Standard Error 0.0145
|
1.333 Liters
Standard Error 0.0151
|
1.374 Liters
Standard Error 0.0148
|
1.385 Liters
Standard Error 0.0148
|
1.243 Liters
Standard Error 0.0156
|
1.370 Liters
Standard Error 0.0145
|
SECONDARY outcome
Timeframe: Day 1FEV1 was measured at 5, 15, 30 minutes, 1, 2, 3, 4, 5, 23 hours and 15 minutes, and 23 hours and 45 minutes post dose.
Outcome measures
| Measure |
NVA237 12.5 ug
n=55 Participants
12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 25 ug
n=51 Participants
25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 50 ug
n=53 Participants
50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 100 ug
n=54 Participants
100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Placebo
n=55 Participants
Placebo via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Tiotropium Bromide
n=55 Participants
18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
|---|---|---|---|---|---|---|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 4 hours
|
1.41 Liters
Standard Error 0.01
|
1.45 Liters
Standard Error 0.01
|
1.49 Liters
Standard Error 0.01
|
1.52 Liters
Standard Error 0.01
|
1.30 Liters
Standard Error 0.01
|
1.46 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Trough
|
1.28 Liters
Standard Error 0.01
|
1.30 Liters
Standard Error 0.01
|
1.36 Liters
Standard Error 0.01
|
1.38 Liters
Standard Error 0.01
|
1.24 Liters
Standard Error 0.01
|
1.36 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: -45 minutes
|
1.25 Liters
Standard Error 0.00
|
1.24 Liters
Standard Error 0.00
|
1.24 Liters
Standard Error 0.00
|
1.24 Liters
Standard Error 0.00
|
1.24 Liters
Standard Error 0.00
|
1.25 Liters
Standard Error 0.00
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: -15 minutes
|
1.25 Liters
Standard Error 0.00
|
1.26 Liters
Standard Error 0.00
|
1.25 Liters
Standard Error 0.00
|
1.26 Liters
Standard Error 0.00
|
1.26 Liters
Standard Error 0.00
|
1.25 Liters
Standard Error 0.00
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 5 minutes
|
1.30 Liters
Standard Error 0.01
|
1.34 Liters
Standard Error 0.01
|
1.34 Liters
Standard Error 0.01
|
1.35 Liters
Standard Error 0.01
|
1.26 Liters
Standard Error 0.01
|
1.31 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 15 minutes
|
1.36 Liters
Standard Error 0.01
|
1.41 Liters
Standard Error 0.01
|
1.41 Liters
Standard Error 0.01
|
1.41 Liters
Standard Error 0.01
|
1.27 Liters
Standard Error 0.01
|
1.35 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 30 minutes
|
1.41 Liters
Standard Error 0.01
|
1.44 Liters
Standard Error 0.01
|
1.44 Liters
Standard Error 0.01
|
1.45 Liters
Standard Error 0.01
|
1.28 Liters
Standard Error 0.01
|
1.40 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 1 hour
|
1.42 Liters
Standard Error 0.01
|
1.46 Liters
Standard Error 0.01
|
1.46 Liters
Standard Error 0.01
|
1.48 Liters
Standard Error 0.01
|
1.28 Liters
Standard Error 0.01
|
1.41 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 2 hours
|
1.44 Liters
Standard Error 0.01
|
1.48 Liters
Standard Error 0.01
|
1.50 Liters
Standard Error 0.01
|
1.52 Liters
Standard Error 0.01
|
1.31 Liters
Standard Error 0.01
|
1.45 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 3 hours
|
1.43 Liters
Standard Error 0.01
|
1.48 Liters
Standard Error 0.01
|
1.49 Liters
Standard Error 0.01
|
1.53 Liters
Standard Error 0.01
|
1.30 Liters
Standard Error 0.01
|
1.46 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 5 hours
|
1.39 Liters
Standard Error 0.01
|
1.43 Liters
Standard Error 0.01
|
1.44 Liters
Standard Error 0.01
|
1.49 Liters
Standard Error 0.01
|
1.28 Liters
Standard Error 0.01
|
1.45 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 23 hours 15 minutes
|
1.27 Liters
Standard Error 0.01
|
1.29 Liters
Standard Error 0.01
|
1.36 Liters
Standard Error 0.01
|
1.37 Liters
Standard Error 0.01
|
1.24 Liters
Standard Error 0.01
|
1.35 Liters
Standard Error 0.01
|
|
Least Squares Means of FEV1 (L) at Day 1, by Timepoint
Day 1: 23 hours 45 minutes
|
1.29 Liters
Standard Error 0.01
|
1.31 Liters
Standard Error 0.01
|
1.37 Liters
Standard Error 0.01
|
1.39 Liters
Standard Error 0.01
|
1.25 Liters
Standard Error 0.01
|
1.37 Liters
Standard Error 0.01
|
Adverse Events
NVA237 12.5 ug
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
NVA237 25 ug
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
NVA237 50 ug
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
NVA237 100 ug
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Tiotropium Bromide
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
NVA237 12.5 ug
n=55 participants at risk
12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 25 ug
n=51 participants at risk
25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 50 ug
n=53 participants at risk
50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 100 ug
n=54 participants at risk
100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Placebo
n=55 participants at risk
Placebo via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Tiotropium Bromide
n=54 participants at risk
18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
|---|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/55
|
0.00%
0/51
|
1.9%
1/53
|
0.00%
0/54
|
0.00%
0/55
|
0.00%
0/54
|
Other adverse events
| Measure |
NVA237 12.5 ug
n=55 participants at risk
12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 25 ug
n=51 participants at risk
25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 50 ug
n=53 participants at risk
50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
NVA237 100 ug
n=54 participants at risk
100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Placebo
n=55 participants at risk
Placebo via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
Tiotropium Bromide
n=54 participants at risk
18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Rhinitis
|
0.00%
0/55
|
5.9%
3/51
|
0.00%
0/53
|
0.00%
0/54
|
1.8%
1/55
|
0.00%
0/54
|
|
Nervous system disorders
Headache
|
7.3%
4/55
|
2.0%
1/51
|
1.9%
1/53
|
1.9%
1/54
|
0.00%
0/55
|
3.7%
2/54
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.5%
3/55
|
0.00%
0/51
|
0.00%
0/53
|
1.9%
1/54
|
3.6%
2/55
|
0.00%
0/54
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
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.
- Publication restrictions are in place
Restriction type: OTHER