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

• ClinicalTrials.gov Identifier: NCT01294787
• Recruitment Status: Completed
• First Posted: February 11, 2011
• Results First Posted: March 20, 2013
• Last Update Posted: March 20, 2013
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
COPD	Drug: indacaterol and glycopyrronium bromide (QVA149); Drug: placebo; Drug: tiotropium	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: February 2011
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: indacaterol and glycopyrronium bromide (QVA149); QVA149 delivered once daily via single-dose dry powder inhaler.	Drug: indacaterol and glycopyrronium bromide (QVA149)
Placebo Comparator: placebo; Placebo, delivered once daily via single-dose dry powder inhaler.	Drug: placebo
Active Comparator: tiotropium; Tiotropium delivered once daily via HandiHaler® device.	Drug: tiotropium

Outcome Measures

Primary Outcome Measures :

1. Exercise Tolerance Comparison Between QVA149 and Placebo Groups [ Time Frame: 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 Outcome Measures :

1. Dynamic Inspiratory Capacity Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
2. Trough 24 Hour Post Dose Inspiratory Capacity Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
3. Trough 24 Hour Post Dose Forced Expiratory Volume in One Second Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
4. Pulmonary Function Test Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
5. Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
6. Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
7. Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
8. Spirometry After Three Weeks of Treatment on Patients Not Exercising [ Time Frame: 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.
9. Exertional Dyspnea Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.

10. Leg Discomfort During Exercise Comparison Between QVA149 and Placebo Groups [ Time Frame: 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.
11. Exercise Endurance Comparison Between QVA149 and Tiotropium Groups [ Time Frame: 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.
12. Exercise Endurance Time Comparison After a Single Dose of QVA149 Versus Placebo [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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/exclusion criteria may apply

Contacts and Locations

Locations

Germany

Novartis Investigative Site

Frankfurt, Germany

Novartis Investigative Site

Grosshansdorf, Germany

Novartis Investigative Site

Hamburg, Germany

Novartis Investigative Site

Lubeck, Germany

Novartis Investigative Site

Mainz, Germany

Novartis Investigative Site

Rudersdorf, Germany

Novartis Investigative Site

Wiesbaden, Germany

Spain

Novartis Investigative Site

Alicante, Spain

Novartis Investigative Site

Badalona, Spain

Novartis Investigative Site

Barakaldo, Spain

Novartis Investigative Site

Barcelona, Spain

Novartis Investigative Site

Madrid, Spain

Novartis Investigative Site

Malaga, Spain

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Beeh KM, Korn S, Beier J, Jadayel D, Henley M, D'Andrea P, Banerji D. Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: the BRIGHT study. Respir Med. 2014 Apr;108(4):584-92. doi: 10.1016/j.rmed.2014.01.006. Epub 2014 Jan 21.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01294787
• Other Study ID Numbers: CQVA149A2305; 2010-022721-14 ( EudraCT Number )
• First Posted: February 11, 2011
• Results First Posted: March 20, 2013
• Last Update Posted: March 20, 2013
• Last Verified: March 2013

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Glycopyrrolate; Bromides; Tiotropium Bromide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Parasympatholytics; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anticonvulsants; Adjuvants, Anesthesia; Muscarinic Antagonists