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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01154127
First received: June 29, 2010
Last updated: April 10, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: NVA237
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks (Day 21) of Treatment [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Day 21 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Day 21 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Day 21 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

    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.



Enrollment: 108
Study Start Date: June 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154127

Locations
United States, South Carolina
Spartanburg Medical Research, 485 Simuel Road
Spartanburg, South Carolina, United States, 29303
Germany
Novartis Investigative Site
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
Italy
Novartis Investigative Site
Verona, Italy
Romania
Novartis Investigative Site
Bucharest, Romania
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01154127     History of Changes
Other Study ID Numbers: CNVA237A2310, 2010-018597-20
Study First Received: June 29, 2010
Results First Received: February 8, 2012
Last Updated: April 10, 2012
Health Authority: Germany: Ministry of Health
Italy: Ethics Committee
Romania: National Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Novartis:
NVA237
COPD
bronchodilator
exercise endurance

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 29, 2014