Back to resultsEffect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD) (GLOW3)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
NVA237
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring NVA237, COPD, bronchodilator, exercise endurance
Eligibility Criteria
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
Sites / Locations
- Spartanburg Medical Research, 485 Simuel Road
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
NVA237 followed by Placebo
Placebo followed by NVA237
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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).
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01154127
Brief Title
Effect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Acronym
GLOW3
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
NVA237, COPD, bronchodilator, exercise endurance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
108 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NVA237 followed by Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo followed by NVA237
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
NVA237
Intervention Description
50 μg via NEOHALER inhaler device single dose dry powder inhaler (SDDPI) once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo via NEOHALER inhaler device single dose dry powder inhaler (SDDPI) once daily
Primary Outcome Measure Information:
Title
Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks (Day 21) of Treatment
Description
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.
Time Frame
Day 21
Secondary Outcome Measure Information:
Title
Isotime Inspiratory Capacity (IC) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment
Description
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.
Time Frame
Day 21
Title
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
Description
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.
Time Frame
Day 21
Title
Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
Description
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.
Time Frame
Day 21
Title
Slow Vital Capacity (SVC) and Total Lung Capacity (TLC)
Description
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).
Time Frame
Day 21
Title
Specific Airways Conductance (SGaw)
Description
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.
Time Frame
Day 21
Title
Exertional Dyspnea (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment
Description
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.
Time Frame
Day 21
Title
Leg Discomfort (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment
Description
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.
Time Frame
Day 21
Title
Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) on Treatment Day 1
Description
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.
Time Frame
Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Spartanburg Medical Research, 485 Simuel Road
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Novartis Investigative Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
Country
Germany
Facility Name
Novartis Investigative Site
City
Mannheim
Country
Germany
Facility Name
Novartis Investigative Site
City
Wiesbaden
Country
Germany
Facility Name
Novartis Investigative Site
City
Woehrendamm
Country
Germany
Facility Name
Novartis Investigative Site
City
Verona
Country
Italy
Facility Name
Novartis Investigative Site
City
Bucharest
Country
Romania
Facility Name
Novartis Investigative Site
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22973092
Citation
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.
Results Reference
derived
Learn more about this trial
Effect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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