Effect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD) (GLOW3)

A Multi-center, Randomized, Double-blind, Placebo-controlled, Two-period Cross-over Study to Assess the Effect of 50µg Inhaled NVA237 on Exercise Endurance in Patients With Moderate to Severe COPD

The ability for patients with COPD to exercise is limited due to the deterioration of their lung function. NVA237 is being developed to treat COPD. This study is designed to look at how well NVA237 improves the ability to exercise in patients with moderate to severe COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: NVA237; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Novartis Investigative Site
  • Frankfurt, Germany
    • Novartis Investigative Site
  • Mainz, Germany
    • Novartis Investigative Site
  • Mannheim, Germany
    • Novartis Investigative Site
  • Wiesbaden, Germany
    • Novartis Investigative Site
  • Woehrendamm, Germany
    • Novartis Investigative Site
• Italy
  • Verona, Italy
    • Novartis Investigative Site
• Romania
  • Bucharest, Romania
    • Novartis Investigative Site
• United Kingdom
  • Manchester, United Kingdom
    • Novartis Investigative Site
• United States
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research, 485 Simuel Road

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:

• Patients who signed an Informed Consent Form prior to initiation of any study-related procedure
• Patients with moderate to severe stable COPD (clinical diagnosis in compliance with GOLD 2008)
• Current or ex-smokers with a smoking history ≥ 10 pack years. (Ten pack-years were defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.).
• Patients with a post-bronchodilator FEV1 ≥ 40 and < 70% of the predicted normal, and postbronchodilator FEV1/FVC < 0.7 during screening. (Post referred to the highest post-bronchodilator value after inhalation of 80 μg ipratropium bromide)
• Increase in FEV1 from pre- to post-bronchodilator assessment of ≥ 5%

Exclusion Criteria:

• Pregnant women or nursing mothers
• Women of child-bearing potential
• Patients who had a COPD exacerbation (whether hospitalized or not) in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 4
• Patients who had a lower respiratory tract infection in the 6 weeks prior to Visit 1
• Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia
• Patients with resting (5 min) oxygen SaO2 (or SpO2) saturation on room air of < 85%
• Patients with a maximum workload (Wmax) value < 20 W (as determined by the incremental cycle endurance test) at Visit 2.
• Patients whose exercise endurance time at sub-maximal workload was above 25 min at baseline
• Patients with a clinically significant abnormality on the screening or baseline ECG who in the judgment of the investigator would have been at potential risk if enrolled into the study
• Patients with a history of long QT syndrome or whose QTc was prolonged (> 450 ms for males and > 470 ms females) at screening (Fredericia's correction)

Other protocol-defined inclusion/exclusion criteria applied

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVA237 followed by Placebo; Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Drug: NVA237; 50 μg via NEOHALER inhaler device single dose dry powder inhaler (SDDPI) once daily; Drug: Placebo; Matching placebo via NEOHALER inhaler device single dose dry powder inhaler (SDDPI) once daily
Experimental: Placebo followed by NVA237; Period 1: Matching placebo of NVA237 via NEOHALER inhaler device for 21 days Period 2: 50 μg NVA237 via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study.	Drug: NVA237; 50 μg via NEOHALER inhaler device single dose dry powder inhaler (SDDPI) once daily; Drug: Placebo; Matching placebo via NEOHALER inhaler device single dose dry powder inhaler (SDDPI) once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks (Day 21) of Treatment	SMETT is an exercise procedure where the patient cycles at 80% of the maximum workload (Wmax )value achieved at the Incremental exercise test. During this test, the patient will cycle at a constant load. Exercise endurance time was from commencement of loaded pedaling to stopping exercise. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Isotime Inspiratory Capacity (IC) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment	Isotime is the last matching timepoint in the submaximal exercise tolerance test (SMETT) at which for both periods the patient has a test result. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21
Inspiratory Capacity (IC) at Rest (1 Hour Post Dose) and at Peak (End of Exercise) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment	IC at peak was observed using spirometry. However, two different methodologies (whole body plethysmography (Bodybox) and spirometry) were used to observe IC at rest. The analysis of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21
Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)	FEV1 is the amount of air that can be exhaled in one second. FEV1 was measured with spirometry conducted according to internationally accepted standards. FVC is the volume of air that can forcibly be blown out after full inspiration and is used in spirometry tests. The trough effects of Day 1 treatment are derived from values prior to morning dosing on the next treatment day (Day 2 of the corresponding period). The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21
Slow Vital Capacity (SVC) and Total Lung Capacity (TLC)	Vital Capacity is the amount of air that can be forcibly exhaled from the lungs after a full inhalation. Slow Vital Capacity (SVC) test is performed by having the patient slowly and completely blow out all of the air from their lungs. Total Lung Capacity (TLC) is the best vital capacity plus residual volume. Whole body plethysmography (Bodybox) was used to measure SVC and TLC. The trough effects of Day 1 treatment are derived from values prior to morning dosing on the next treatment day (Day 2 of the corresponding period).	Day 21
Specific Airways Conductance (SGaw)	SGaw is a measure of how hard it is to get air into the lungs, measured by (Sec(-1)*kP). Whole body plethysmography (Bodybox) was used to measure SGaw. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21
Exertional Dyspnea (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment	The Borg CR10 Scale consists of 12-point score that the patients 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. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21
Leg Discomfort (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment	The modified Borg CR10 Scale consists of 12-point score that the patients pointed to so as to indicate their level of leg discomfort 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. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 21
Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) on Treatment Day 1	SMETT is an exercise procedure where the patient cycles at 80% of the maximum workload (Wmax )value achieved at the Incremental exercise test. During this test, the patient will cycle at a constant load. Exercise endurance time was from commencement of loaded pedaling to stopping exercise. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.	Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Beeh KM, Singh D, Di Scala L, Drollmann A. Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial. Int J Chron Obstruct Pulmon Dis. 2012;7:503-13. doi: 10.2147/COPD.S32451. Epub 2012 Jul 31.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: June 29, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Estimate): May 7, 2012
• Last Update Submitted That Met QC Criteria: April 10, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: COPD; NVA237; bronchodilator; exercise endurance
• 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; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: CNVA237A2310; 2010-018597-20 (EudraCT Number)