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

June 29, 2010
April 10, 2012
June 2010
February 2011   (final data collection date for primary outcome measure)
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.
Measure: To determine the effect of 50µg NVA237 compared with matched placebo inhaled once daily on exercise tolerance as measured by exercise endurance time during a sub-maximal constant-load cycle ergometry test (SMETT). [ Time Frame: Three weeks after treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01154127 on ClinicalTrials.gov Archive Site
  • 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.

  • Measure: To determine the effect of 50µg NVA237 compared with placebo on isotime inspiratory capacity (IC) during SMETT. [ Time Frame: Three weeks after treatment ] [ Designated as safety issue: No ]
  • Measure: To determine the effect of 50 µg NVA237 compared with placebo on inspiratory capacity at rest and at peak during SMETT. [ Time Frame: Three weeks after treatment ] [ Designated as safety issue: No ]
  • Measure: To evaluate the effects of 5050µg NVA237 compared with placebo on exertional dyspnea during SMETT [ Time Frame: Three weeks after treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Effect of NVA237 on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Chronic Obstructive Pulmonary Disease
  • 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: 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.

    Interventions:
    • Drug: NVA237
    • Drug: Placebo
  • 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.

    Interventions:
    • Drug: NVA237
    • Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
108
February 2011
February 2011   (final data collection date for primary outcome measure)

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

Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany,   United Kingdom,   Italy,   Romania,   United States
 
NCT01154127
CNVA237A2310, 2010-018597-20
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP