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

A Randomized, Blinded, Double Dummy, Multi-center, Placebo Controlled, 3 Period, Crossover Study to Assess the Effect of QVA149 (110/50 µg o.d.) on Exercise Endurance in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01294787

Acronym

BRIGHT

Enrollment

Registered

2011-02-11

Start date

2011-02-28

Completion date

2011-11-30

Last updated

2013-03-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD

Keywords

COPD, QVA149, tiotropium, exercise, exercise tolerance, combination bronchodilator, moderate to severe COPD

Brief summary

This study assessed the effect of once-daily indacaterol and glycopyrronium bromide (QVA149) on exercise endurance in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Interventions

DRUGindacaterol and glycopyrronium bromide (QVA149)

DRUGplacebo

DRUGtiotropium

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD) stage II or stage III according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines (2009) * Qualifying spirometry, Forced Expiratory Volume in one second (FEV1) and post-bronchodilator FEV1/FVC (Forced Vital capacity) * Smoking history ≥ 10 pack years

Exclusion criteria

* Pregnant women or nursing mothers or women of child-bearing potential not using adequate contraception * Cardiac abnormality * History of asthma * Contraindications to cardiopulmonary exercise testing * Participation in active phase of pulmonary rehabilitation program * History of cancer within the past 5 years Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Exercise Tolerance Comparison Between QVA149 and Placebo Groups	3 weeks	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.

Secondary

Measure	Time frame	Description
Trough 24 Hour Post Dose Inspiratory Capacity Comparison Between QVA149 and Placebo Groups	3 weeks	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.
Trough 24 Hour Post Dose Forced Expiratory Volume in One Second Comparison Between QVA149 and Placebo Groups	3 weeks	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.
Pulmonary Function Test Comparison Between QVA149 and Placebo Groups	day 1 and day 21	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.
Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups	day 1 and day 21	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.
Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups	day 1 and day 21	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.
Dynamic Inspiratory Capacity Comparison Between QVA149 and Placebo Groups	3 weeks	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.
Spirometry After Three Weeks of Treatment on Patients Not Exercising	3 weeks	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.
Exertional Dyspnea Comparison Between QVA149 and Placebo Groups	3 weeks	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.
Leg Discomfort During Exercise Comparison Between QVA149 and Placebo Groups	3 weeks	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.
Exercise Endurance Comparison Between QVA149 and Tiotropium Groups	3 weeks	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.
Exercise Endurance Time Comparison After a Single Dose of QVA149 Versus Placebo	Day 1	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).
Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups	day 1 and day 21	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.

Countries

Germany, Spain

Participant flow

Recruitment details

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.

Pre-assignment details

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.

Participants by arm

Arm	Count
All 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.	84
Total	84

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG003	FG004	FG005
Period 1	Administrative problem	0	1	0	0	1
Period 1	Adverse Event	0	0	0	1	0
Period 1	Withdrawal by Subject	0	0	1	1	1
Period 2	Adverse Event	3	0	1	0	0
Period 2	No longer needs study drug	0	0	1	0	0
Period 3	Adverse Event	0	0	0	1	0

Baseline characteristics

Characteristic	All Participants
Age Continuous All participants	62.1 years STANDARD_DEVIATION 8.11
Sex: Female, Male Female	53 Participants
Sex: Female, Male Male	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	11 / 77	5 / 83	4 / 77
serious Total, serious adverse events	1 / 77	1 / 83	1 / 77

Outcome results

Primary

Exercise Tolerance Comparison Between QVA149 and Placebo Groups

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.

Time frame: 3 weeks