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Trial Outcomes & Findings for Effect of QVA149 on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01294787)

NCT ID: NCT01294787

Last Updated: 2013-03-20

Results Overview

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured by exercise endurance time (in seconds) during a sub-maximal constant load cycle ergometry test ((SMETT)which is a cycle exercise test) after three weeks of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

85 participants

Primary outcome timeframe

3 weeks

Results posted on

2013-03-20

Participant Flow

The study consisted of a maximum 28 day screening period, and three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.

A total of 85 patients were randomized and 73 patients completed the study. Since this was a cross-over study a participant may be counted in more than 1 group: 77 participants were treated with QVA149, 83 participants treated with tiotropium and 77 participants treated with placebo. One randomized patient did not receive study drug.

Participant milestones

Participant milestones
Measure
QVA149 / Placebo / Tiotropium
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
QVA149 / Tiotropium / Placebo
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Placebo / QVA149 / Tiotropium
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Placebo / Tiotropium / QVA149
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Tiotropium / QAV149 / Placebo
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Tiotropium / Placebo / QVA149
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Period 1
STARTED
12
16
14
12
16
15
Period 1
COMPLETED
12
16
13
11
14
13
Period 1
NOT COMPLETED
0
0
1
1
2
2
Period 2
STARTED
12
16
13
11
14
13
Period 2
COMPLETED
12
13
13
9
14
13
Period 2
NOT COMPLETED
0
3
0
2
0
0
Period 3
STARTED
12
13
13
9
14
13
Period 3
COMPLETED
12
13
13
9
13
13
Period 3
NOT COMPLETED
0
0
0
0
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
QVA149 / Placebo / Tiotropium
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
QVA149 / Tiotropium / Placebo
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Placebo / QVA149 / Tiotropium
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Placebo / Tiotropium / QVA149
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Tiotropium / QAV149 / Placebo
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Tiotropium / Placebo / QVA149
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods.
Period 1
Adverse Event
0
0
0
0
1
0
Period 1
Withdrawal by Subject
0
0
0
1
1
1
Period 1
Administrative problem
0
0
1
0
0
1
Period 2
Adverse Event
0
3
0
1
0
0
Period 2
No longer needs study drug
0
0
0
1
0
0
Period 3
Adverse Event
0
0
0
0
1
0

Baseline Characteristics

Effect of QVA149 on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Participants
n=84 Participants
Participants received three, 3-week treatment periods followed by a study completion evaluation. A washout of 21 days was used to separate the treatment periods. One participant was randomized but did not receive study drug.
Sex: Female, Male
Male
31 Participants
n=99 Participants
Age Continuous
All participants
62.1 years
STANDARD_DEVIATION 8.11 • n=99 Participants
Sex: Female, Male
Female
53 Participants
n=99 Participants

PRIMARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured by exercise endurance time (in seconds) during a sub-maximal constant load cycle ergometry test ((SMETT)which is a cycle exercise test) after three weeks of treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=74 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
Placebo, delivered once daily via single-dose dry powder inhaler.
Exercise Tolerance Comparison Between QVA149 and Placebo Groups
507.8 Seconds
Standard Error 19.30
448.3 Seconds
Standard Error 19.49
—

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using dynamic inspiratory capacity at isotime during sub-maximal constant load cycle ergometry test ((SMETT)a cycle exercise test), after three weeks of treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=65 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=67 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=59 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Dynamic Inspiratory Capacity Comparison Between QVA149 and Placebo Groups
2.42 Liters
Standard Error 0.034
2.29 Liters
Standard Error 0.033
2.11 Liters
Standard Error 0.035

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using trough 24 hour post dose inspiratory capacity after three weeks of treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=67 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=73 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=66 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Trough 24 Hour Post Dose Inspiratory Capacity Comparison Between QVA149 and Placebo Groups
2.25 Liters
Standard Error 0.035
2.10 Liters
Standard Error 0.034
2.06 Liters
Standard Error 0.035

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using trough 24 hour post dose Forced Expiratory Volume in one second (FEV1) after three weeks of treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=76 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=78 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=73 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Trough 24 Hour Post Dose Forced Expiratory Volume in One Second Comparison Between QVA149 and Placebo Groups
1.53 Liters
Standard Error 0.020
1.43 Liters
Standard Error 0.020
1.33 Liters
Standard Error 0.021

SECONDARY outcome

Timeframe: day 1 and day 21

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Slow Vital Capacity (SVC) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography.

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=83 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=77 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Pulmonary Function Test Comparison Between QVA149 and Placebo Groups
Day 1- 15 min post-dose
3.43 Liters
Standard Error 0.026
3.32 Liters
Standard Error 0.025
3.16 Liters
Standard Error 0.026
Pulmonary Function Test Comparison Between QVA149 and Placebo Groups
Day 21- 5 min post-dose
3.37 Liters
Standard Error 0.037
3.26 Liters
Standard Error 0.036
3.08 Liters
Standard Error 0.038
Pulmonary Function Test Comparison Between QVA149 and Placebo Groups
Day 21- 15 min post-dose
3.38 Liters
Standard Error 0.040
3.29 Liters
Standard Error 0.038
3.09 Liters
Standard Error 0.039
Pulmonary Function Test Comparison Between QVA149 and Placebo Groups
Day 1- 5 min post-dose
3.37 Liters
Standard Error 0.028
3.22 Liters
Standard Error 0.027
3.14 Liters
Standard Error 0.028

SECONDARY outcome

Timeframe: day 1 and day 21

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Residual Volume (RV) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography.

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=83 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=77 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups
Day 1 - 5 min post-dose
3.66 Liters
Standard Error 0.051
3.89 Liters
Standard Error 0.048
3.94 Liters
Standard Error 0.050
Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups
Day 1 - 15 min post-dose
3.63 Liters
Standard Error 0.048
3.66 Liters
Standard Error 0.046
3.89 Liters
Standard Error 0.048
Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups
Day 21- 5 min post-dose
3.58 Liters
Standard Error 0.063
3.69 Liters
Standard Error 0.061
4.03 Liters
Standard Error 0.064
Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups
Day 21- 15 min post-dose
3.54 Liters
Standard Error 0.066
3.59 Liters
Standard Error 0.062
3.96 Liters
Standard Error 0.065

SECONDARY outcome

Timeframe: day 1 and day 21

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Specific Airway Conductance (SGaw) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography.

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=83 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=77 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups
Day 1- 5 min post-dose
0.71 Kilo Pascal per second
Standard Error 0.035
0.58 Kilo Pascal per second
Standard Error 0.033
0.50 Kilo Pascal per second
Standard Error 0.035
Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups
Day 1- 15 min post-dose
0.71 Kilo Pascal per second
Standard Error 0.064
0.79 Kilo Pascal per second
Standard Error 0.061
0.50 Kilo Pascal per second
Standard Error 0.063
Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups
Day 21- 5 min post-dose
0.76 Kilo Pascal per second
Standard Error 0.041
0.64 Kilo Pascal per second
Standard Error 0.039
0.50 Kilo Pascal per second
Standard Error 0.041
Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups
Day 21- 15 min post-dose
0.79 Kilo Pascal per second
Standard Error 0.039
0.67 Kilo Pascal per second
Standard Error 0.038
0.47 Kilo Pascal per second
Standard Error 0.038

SECONDARY outcome

Timeframe: day 1 and day 21

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Functional Residual Capacity (FRC) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography.

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=83 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=77 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups
Day 1- 5 min post-dose
4.68 Liters
Standard Error 0.057
4.78 Liters
Standard Error 0.055
4.98 Liters
Standard Error 0.057
Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups
Day 1- 15 min post-dose
4.62 Liters
Standard Error 0.060
4.63 Liters
Standard Error 0.058
4.92 Liters
Standard Error 0.059
Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups
Day 21- 5 min post-dose
4.58 Liters
Standard Error 0.068
4.66 Liters
Standard Error 0.066
5.00 Liters
Standard Error 0.068
Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups
Day 21- 15 min post-dose
4.53 Liters
Standard Error 0.067
4.55 Liters
Standard Error 0.065
4.91 Liters
Standard Error 0.067

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using dynamic inspiratory capacity post-dose pre-exercise after three weeks of treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=76 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=80 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=70 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Spirometry After Three Weeks of Treatment on Patients Not Exercising
2.34 Liters
Standard Error 0.032
2.19 Liters
Standard Error 0.031
2.01 Liters
Standard Error 0.033

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using exertional dyspnea Borg CR10 Scale® (After 3 weeks of treatment, before, during and after exercise, patients were asked to rate the intensity of their breathing and leg discomfort using the Borg CR10 Scale®). This scale consists of 12-point score that the participants pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 12 indicates maximum breathlessness). A reduction in this score indicates an improvement.

Outcome measures

Outcome measures
Measure
QVA149
n=66 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=70 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=61 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Exertional Dyspnea Comparison Between QVA149 and Placebo Groups
3.77 units on a scale
Standard Error 0.256
3.59 units on a scale
Standard Error 0.248
3.87 units on a scale
Standard Error 0.259

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo on leg discomfort was measured using Borg CR10 Scale® during sub-maximal constant load cycle ergometry test after three weeks treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=66 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=70 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=61 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Leg Discomfort During Exercise Comparison Between QVA149 and Placebo Groups
4.53 units on a scale
Standard Error 0.243
4.57 units on a scale
Standard Error 0.234
4.43 units on a scale
Standard Error 0.245

SECONDARY outcome

Timeframe: 3 weeks

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Effect of QVA149 110/50 µg o.d. compared with tiotropium 18 µg o.d. in patients with moderate to severe COPD with respect to exercise endurance was measured by a sub-maximal constant load cycle ergometry test ((SMETT)cycle exercise test) after three weeks of treatment.

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=80 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
Placebo, delivered once daily via single-dose dry powder inhaler.
Exercise Endurance Comparison Between QVA149 and Tiotropium Groups
507.8 Seconds
Standard Error 19.30
514 Seconds
Standard Error 18.99
—

SECONDARY outcome

Timeframe: Day 1

Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

The effect of a single dose of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured with respect to exercise endurance time during sub-maximal constant load cycle ergometry test ((SMETT)cycle exercise test).

Outcome measures

Outcome measures
Measure
QVA149
n=77 Participants
Indacaterol and glycopyrronium bromide (QVA149) delivered once daily via single-dose dry powder inhaler.
Placebo
n=83 Participants
Placebo, delivered once daily via single-dose dry powder inhaler
Placebo
n=77 Participants
Placebo, delivered once daily via single-dose dry powder inhaler.
Exercise Endurance Time Comparison After a Single Dose of QVA149 Versus Placebo
492.8 Seconds
Standard Error 17.28
481.0 Seconds
Standard Error 16.77
468.8 Seconds
Standard Error 17.18

Adverse Events

Indacaterol and Glycopyrronium Bromide (QVA149)

Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths

Tiotropium

Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Indacaterol and Glycopyrronium Bromide (QVA149)
n=77 participants at risk
QVA149 delivered once daily via single-dose dry powder inhaler.
Tiotropium
n=83 participants at risk
Tiotropium delivered once daily via HandiHaler® device.
Placebo
n=77 participants at risk
Placebo, delivered once daily via single-dose dry powder inhaler.
Cardiac disorders
Acute myocardial infarction
0.00%
0/77
1.2%
1/83
0.00%
0/77
Gastrointestinal disorders
Colitis
1.3%
1/77
0.00%
0/83
0.00%
0/77
Infections and infestations
Pneumonia
0.00%
0/77
0.00%
0/83
1.3%
1/77

Other adverse events

Other adverse events
Measure
Indacaterol and Glycopyrronium Bromide (QVA149)
n=77 participants at risk
QVA149 delivered once daily via single-dose dry powder inhaler.
Tiotropium
n=83 participants at risk
Tiotropium delivered once daily via HandiHaler® device.
Placebo
n=77 participants at risk
Placebo, delivered once daily via single-dose dry powder inhaler.
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
9.1%
7/77
6.0%
5/83
3.9%
3/77
Respiratory, thoracic and mediastinal disorders
Cough
6.5%
5/77
0.00%
0/83
1.3%
1/77

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 41 61 324 1111

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