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

• ClinicalTrials.gov Identifier: NCT01154127
• Recruitment Status: Completed
• First Posted: June 30, 2010
• Results First Posted: May 7, 2012
• Last Update Posted: May 7, 2012
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: NVA237; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, 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
• Study Start Date: June 2010
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks (Day 21) of Treatment [ Time Frame: Day 21 ]
   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 :

1. Isotime Inspiratory Capacity (IC) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks of Treatment [ Time Frame: Day 21 ]
   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.
2. 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 ]

   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.

3. Peak and Trough (24 h Post Dose) Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) [ Time Frame: Day 21 ]

   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.

4. Slow Vital Capacity (SVC) and Total Lung Capacity (TLC) [ Time Frame: Day 21 ]

   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).

5. Specific Airways Conductance (SGaw) [ Time Frame: Day 21 ]

   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.

6. Exertional Dyspnea (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment [ Time Frame: Day 21 ]

   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.

7. Leg Discomfort (Borg CR10 Scale) During Sub-maximal Constant-load Cycle Ergometry Test (SMETT) After 3 Weeks Treatment [ Time Frame: Day 21 ]

   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.

8. Exercise Endurance Time During a Sub-maximal Constant-load Cycle Ergometry Test (SMETT) on Treatment Day 1 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01154127
• Other Study ID Numbers: CNVA237A2310; 2010-018597-20 ( EudraCT Number )
• First Posted: June 30, 2010
• Results First Posted: May 7, 2012
• Last Update Posted: May 7, 2012
• Last Verified: April 2012

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

NVA237; COPD; bronchodilator; exercise endurance

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Glycopyrrolate; Adjuvants, Anesthesia; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs