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

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.

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).

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: placebo; Drug: tiotropium; Drug: indacaterol and glycopyrronium bromide (QVA149)

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • 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
    • Novartis Investigative Site
• Spain
  • 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
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: February 10, 2011
• First Posted (Estimate): February 11, 2011

Study Record Updates

• Last Update Posted (Estimate): March 20, 2013
• Last Update Submitted That Met QC Criteria: March 19, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: exercise; COPD; exercise tolerance; QVA149; combination bronchodilator; tiotropium; moderate to severe COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Glycopyrrolate; Tiotropium Bromide; Bromides
• Other Study ID Numbers: CQVA149A2305; 2010-022721-14 (EudraCT Number)