Trial Outcomes & Findings for Bronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma (NCT NCT03137784)
NCT ID: NCT03137784
Last Updated: 2019-01-16
Results Overview
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared to placebo in terms of trough FEV1 (mean of 23h 15 min and 23 h 45 min post -dose) following 1 week of treatment in the respective treatment period. Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 15 min and 23h 45 min post dose.
COMPLETED
PHASE2/PHASE3
148 participants
Following 1 week of treatment
2019-01-16
Participant Flow
Participant milestones
| Measure |
1(NVA237 50 ug/NVA237 25 ug/Placebo)
Treatment sequence: NVA 237 50 ug, 25 ug and placebo
|
2(NVA237 50 ug/Placebo/NVA237 25 ug)
Treatment sequence: NVA 237 50 ug, placebo and 25 ug
|
3 (NVA237 25 ug/NVA237 50 ug/Placebo)
Treatment sequence: NVA237 25 ug, 50 ug and placebo
|
4 (NVA237 25 ug/Placebo/NVA237 50 ug)
Treatment sequence: NVA 237 25 ug, placebo and 50 ug
|
5 (Placebo/NVA237 50 ug/ NVA237 25 ug)
Treatment sequence: Placebo, NVA237 50 ug and 25 ug
|
6 (Placebo/ NVA237 25 ug/NVA237 50 ug)
Treatment sequence: placebo, NVA237 25 ug and 50 ug
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
24
|
25
|
25
|
24
|
25
|
25
|
|
Overall Study
COMPLETED
|
22
|
24
|
25
|
24
|
24
|
25
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
1(NVA237 50 ug/NVA237 25 ug/Placebo)
Treatment sequence: NVA 237 50 ug, 25 ug and placebo
|
2(NVA237 50 ug/Placebo/NVA237 25 ug)
Treatment sequence: NVA 237 50 ug, placebo and 25 ug
|
3 (NVA237 25 ug/NVA237 50 ug/Placebo)
Treatment sequence: NVA237 25 ug, 50 ug and placebo
|
4 (NVA237 25 ug/Placebo/NVA237 50 ug)
Treatment sequence: NVA 237 25 ug, placebo and 50 ug
|
5 (Placebo/NVA237 50 ug/ NVA237 25 ug)
Treatment sequence: Placebo, NVA237 50 ug and 25 ug
|
6 (Placebo/ NVA237 25 ug/NVA237 50 ug)
Treatment sequence: placebo, NVA237 25 ug and 50 ug
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Subject/guardian decision
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Non-compliance with study treatment
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Bronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma
Baseline characteristics by cohort
| Measure |
All Participants
n=148 Participants
All participants randomized to one of six treatment sequences
|
|---|---|
|
Age, Continuous
|
47.3 Years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
75 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
73 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
120 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence.
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared to placebo in terms of trough FEV1 (mean of 23h 15 min and 23 h 45 min post -dose) following 1 week of treatment in the respective treatment period. Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 15 min and 23h 45 min post dose.
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Trough FEV1 After One Week of Treatment, Point Estimate
|
2.392 Liters
Standard Error 0.0249
|
2.392 Liters
Standard Error 0.0250
|
2.303 Liters
Standard Error 0.0247
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence.
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 5min-1h)
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
FEV1 AUC (5 Min-1 h) After One Week of Treatment
|
2.489 Liters
Standard Error 0.0226
|
2.492 Liters
Standard Error 0.0228
|
2.324 Liters
Standard Error 0.0227
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence.
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 5min-4h)
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
FEV1 AUC (5 Min-4 h) After One Week of Treatment
|
2.522 Liters
Standard Error 0.0223
|
2.525 Liters
Standard Error 0.0224
|
2.346 Liters
Standard Error 0.0223
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence.
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day AUC (5 min - 23 h 45 min)
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
FEV1 AUC (5 Min - 23 h 45 Min) After One Week of Treatment
|
2.443 Liters
Standard Error 0.0226
|
2.450 Liters
Standard Error 0.0227
|
2.304 Liters
Standard Error 0.0226
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Peak FEV1 following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect following 1 week of treatment was defined as the maximum FEV1 during the first 4 hour on that day.
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Peak FEV1 During 4 Hours Post-dose After 1 Week of Treatment
|
2.621 Liters
Standard Error 0.0228
|
2.630 Liters
Standard Error 0.0229
|
2.457 Liters
Standard Error 0.0228
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FVC following 1 week of treatment in respective treatment period. Trough Forced Vital Capacity (FVC) following 7 Days. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Trough Forced Vital Capacity (FVC) After 1 Week of Treatment
|
3.509 Liters
Standard Error 0.0268
|
3.530 Liters
Standard Error 0.0269
|
3.472 Liters
Standard Error 0.0267
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FEV1/FVC ratio following 1 week of treatment in respective treatment period
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Percent Change From Baseline in FEV1/FVC Ratio
|
0.018 Percent change
Standard Deviation 0.0421
|
0.016 Percent change
Standard Deviation 0.0438
|
0.003 Percent change
Standard Deviation 0.0398
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Mean Morning Peak Expiratory Flow (PEF) Following the 1-week Treatment Period
|
395.09 L/min
Standard Error 2.948
|
393.87 L/min
Standard Error 2.962
|
369.58 L/min
Standard Error 2.958
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits. LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Mean Evening Peak Expiratory Flow Rate (PEF) Following 1-week Treatment
|
409.66 L/min
Standard Error 2.928
|
408.08 L/min
Standard Error 2.934
|
378.72 L/min
Standard Error 2.949
|
SECONDARY outcome
Timeframe: Following 1 week of treatmentPopulation: The Full Analysis Set (FAS) consisted of all patients in the randomized Set (RAN) who received at least one dose of study medication. Following the intent-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence
A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. daytime and nighttime (combined) number of puffs is defined as the average of the respective number of puffs.
Outcome measures
| Measure |
NVA237 50 ug
n=147 Participants
NVA237 50 g capsule
|
NVA237 25 ug
n=146 Participants
NVA237 25 μg capsule
|
Placebo
n=146 Participants
Placebo
|
|---|---|---|---|
|
Mean Daily Number of Puffs of Rescue Medication During 1 Week of Treatment
|
0.98 Puffs/day
Standard Error 0.094
|
1.02 Puffs/day
Standard Error 0.094
|
1.13 Puffs/day
Standard Error 0.094
|
Adverse Events
NVA237 50 ug
NVA237 25 ug
Placebo
Serious adverse events
| Measure |
NVA237 50 ug
n=147 participants at risk
NVA237 50 ug capsule
|
NVA237 25 ug
n=146 participants at risk
NVA237 25 ug capsule
|
Placebo
n=146 participants at risk
Placebo
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Patellofemoral pain syndrome
|
0.68%
1/147 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/147 • Following 1 week of treatment
AE additional description
|
0.68%
1/146 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
Other adverse events
| Measure |
NVA237 50 ug
n=147 participants at risk
NVA237 50 ug capsule
|
NVA237 25 ug
n=146 participants at risk
NVA237 25 ug capsule
|
Placebo
n=146 participants at risk
Placebo
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
1.4%
2/147 • Following 1 week of treatment
AE additional description
|
0.68%
1/146 • Following 1 week of treatment
AE additional description
|
2.1%
3/146 • Following 1 week of treatment
AE additional description
|
|
Infections and infestations
Upper respiratory tract infection
|
0.68%
1/147 • Following 1 week of treatment
AE additional description
|
2.1%
3/146 • Following 1 week of treatment
AE additional description
|
0.68%
1/146 • Following 1 week of treatment
AE additional description
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.68%
1/147 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
|
Nervous system disorders
Dizziness
|
0.68%
1/147 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
|
Nervous system disorders
Headache
|
3.4%
5/147 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/147 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.68%
1/147 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
0.00%
0/146 • Following 1 week of treatment
AE additional description
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/147 • Following 1 week of treatment
AE additional description
|
1.4%
2/146 • Following 1 week of treatment
AE additional description
|
0.68%
1/146 • Following 1 week of treatment
AE additional description
|
Additional Information
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