1-year Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease Clinical Trial

— GLOW2  

Official title:

A 52-week Treatment, Randomized, Double-blind, Placebo-controlled, With Open-label Tiotropium, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Patients With Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00929110
• Other study ID #: CNVA237A2303
• Secondary ID: 2008-008394-63
• Status: Completed
• Phase: Phase 3
• First received: June 25, 2009
• Last updated: August 9, 2012
• Start date: June 2009
• Est. completion date: April 2011

Study information

• Verified date: August 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaChile: Comisión Nacional de Investigación Científica y TecnológicaColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIsrael: Ministry of HealthItaly: The Italian Medicines AgencyKorea: Food and Drug AdministrationMalaysia: Ministry of HealthMexico: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)New Zealand: Food Safety AuthorityPeru: Ministry of HealthPhilippines: Bureau of Food and DrugsPoland: Ministry of HealthRussia: Ministry of Health of the Russian FederationSouth Africa: Department of HealthThailand: Food and Drug AdministrationTurkey: Ministry of HealthUkraine: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This study was designed to investigate the 1 year efficacy and safety of the 50 µg once daily (od) dose of glycopyrronium bromide (NVA237) in patients with moderate to severe chronic obstructive pulmonary disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1066
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Male or female adults aged = 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.

2. Patients with moderate to severe stable chronic obstructive pulmonary disease (COPD, Stage II or Stage III) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008.

3. Current or ex-smokers who have a smoking history of at least 10 pack years.

4. Patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) = 30% and < 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) < 0.7 at Visit 2 (Day -14).

5. Patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3 (Day 1).

Exclusion Criteria:

1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).

2. Women of child-bearing potential, unless using an approved method of medical or surgical contraception.

3. Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia, or who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 1 (Day -21) or between Visit 1 (Day -21) and Visit 3 (Day 1).

4. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1 (Day -21).

5. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition.

6. Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 600/mm^3 (at Visit 1, Day -21) and onset of symptoms prior to age 40 years.

7. Patients with a history of long QT syndrome or whose QTc measured at Visit 1 (Day -21) (Fridericia method) is prolonged (> 450 ms for males or > 470 ms for females.

Other protocol-defined inclusion/exclusion criteria may apply to the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Glycopyrronium bromide
Glycopyrronium bromide was supplied in powder-filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
• Placebo to glycopyrronium bromide
Placebo to glycopyrronium bromide was supplied in powder-filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
• Tiotropium
Tiotropium was supplied in powder-filled capsules together with the Handihaler® device.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal
Argentina	Novartis Investigative Site	La Plata - Bueno Aire
Argentina	Novartis Investigative Site	Parana Entre Rios
Argentina	Novartis Investigative Site	Rosario
Argentina	Novartis Investigative Site	Tucuman
Canada	Novartis Investigator Site	Brampton
Canada	Novartis Investigator Site	Calgary
Canada	Novartis Investigator Site	Edmonton
Canada	Novartis Investigator Site	Kelowna
Canada	Novartis Investigator Site	Langley
Canada	Novartis Investigator Site	Niagara Falls
Canada	Novartis Investigator Site	Quebec
Canada	Novartis Investigator Site	Ste-Foy
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Talcahuano
Chile	Novartis Investigative Site	Vina del Mar
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Rennes Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Landsberg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Munich
Hungary	Novartis Investigative Site	Gyonsyos
Hungary	Novartis Investigative Site	Siokok
Israel	Novartis Investigative Site	Be'er Sheva
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Rehovot
Italy	Novartis Investigative Site	Firenze
Italy	Novartis Investigative Site	Monza
Italy	Novartis Investigative Site	Parma
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Gyeonggi-go
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Mexico	Novartis Investigative Site	Guadalajara
Mexico	Novartis Investigative Site	Monterrey
Mexico	Novartis Investigative Site	San Luis Potosi
Netherlands	Novartis Investigative Site	Sneek
New Zealand	Novartis Investigator Site	Auckland
New Zealand	Novartis Investigator Site	Christchurch
New Zealand	Novartis Investigator Site	Hamilton
New Zealand	Novartis Investigator Site	Tauranga
New Zealand	Novartis Investigator Site	Wellington
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Santiago de Surco
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Bystra
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Ostrow Wielkopolski
Poland	Novartis Investigative Site	Piekary Slaskic
Poland	Novartis Investigative Site	Tarnow
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Irkutsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	Volgograd
Russian Federation	Novartis Investigative Site	Yaroslavl
United States	Novartis Investigator Site	Anaheim	California
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigator Site	Austin	Texas
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Blue Ridge	Georgia
United States	Novartis Investigator Site	Boys Town	Maine
United States	Novartis Investigator Site	Bozeman	Montana
United States	Novartis Investigative site	Charlotte	North Carolina
United States	Novartis Investigative Site	Charlottesville	Virginia
United States	Novartis Investigator Site	Cincinnati	Ohio
United States	Novartis Investigator Site	Coeur D'Alene	Idaho
United States	Novartis Investigator Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Columbia	Maryland
United States	Novartis Investigator Site	Council Bluffs	Iowa
United States	Novartis Investigative Center	Crescent Springs	Kentucky
United States	Novartis Investigative Site	Crestview Hills	Kentucky
United States	Novartis Investigative site	DeLand	Florida
United States	Novartis Investigative Site	Downingtown	Pennsylvania
United States	Novartis Investigative Site	Duluth	Georgia
United States	Novartis Investigative Site	East Providence	Rhode Island
United States	Novartis Investigator Site	El Paso	Texas
United States	Novartis Investigative Site	Endwell	New York
United States	Novartis Investigator Site	Fort Smith	Arkansas
United States	Novartis Investigative Site	Ft. Lauderdale	Florida
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Hazard	Kentucky
United States	Novartis Investigator Site	Iowa City	Iowa
United States	Novartis Investigator Site	Lafayette	Louisiana
United States	Novartis Investigative Site	Lakewood	California
United States	Novartis Investigator Site	Lincoln	Nebraska
United States	Novartis Investigator Site	Los Angeles	California
United States	Novartis Investigator Site	Los Angeles	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigator Site	Medford	Oregon
United States	Novartis Investigator Site	Medford	Oregon
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami Beach	Florida
United States	Novartis Investigator Site	Milwaukee	Wisconsin
United States	Novartis Investigator Site	Minneapolis	Minnesota
United States	Novartis Investigator Site	Mission Viejo	California
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Montgomery	Alabama
United States	Novartis Investigator Site	New Albany	Indiana
United States	Novartis Investigator Site	New Braunfels	Texas
United States	Novartis Investigative Site	North Charleston	South Carolina
United States	Novartis Investigative Site	North Dartmouth	Massachusetts
United States	Novartis Investigative Site	Ocala	Florida
United States	Novartis Investigator Site	Oklahoma City	Oklahoma
United States	Novartis Investigator Site	Oklahoma City	Oklahoma
United States	Novartis Investigator Site	Omaha	Nebraska
United States	Novartis Investigative Site	Panama City	Florida
United States	Novartis Investigator Site	Papillion	Nebraska
United States	Novartis Investigator Site	Paramount	California
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigator Site	Portland	Oregon
United States	Novartis Investigator Site	Portland	Oregon
United States	Novartis Investigative Site	Providence	Rhode Island
United States	Novartis Investigator Site	Provo	Utah
United States	Novartis Investigator Site	Riverside	California
United States	Novartis Investigative Site	Rolling Hills Estates	California
United States	Novartis Investigator Site	San Antonio	Texas
United States	Novartis Investigator Site	San Diego	California
United States	Novartis Investigator Site	Shawnee	Kansas
United States	Novartis Investigative Site	Skillman	New Jersey
United States	Novartis Investigator Site	Skokie	Illinois
United States	Novartis Investigator Site	St. Louis	Missouri
United States	Novartis Investigator Site	Sunset	Louisiana
United States	Novartis Investigator Site	Sylvania	Ohio
United States	Novartis Investigator Site	Tacoma	Washington
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Taunton	Massachusetts
United States	Novartis Investigator Site	Toledo	Ohio
United States	Novartis Investigator Site	Valparaiso	Indiana
United States	Novartis Investigative Site	Wheaton	Maryland
United States	Novartis Investigator Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Peru,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included baseline FEV1 measurement, baseline inhaled corticosteroid use (Yes/No), FEV1 prior to inhalation of short-acting ß2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.	Week 12	No
Secondary	Transition Dyspnea Index (TDI) at Week 26	The TDI measured changes in dyspnea from baseline during treatment and included 3 domains: Functional impairment (activities of daily living), magnitude of task (intensity of activity), and magnitude of effort (difficulty breathing). Each domain was rated from -3 to 3 (major deterioration-major improvement). The total score ranged from -9 to 9; minus scores indicate deterioration. The analysis included the same covariates as the primary Outcome Measure.	Week 26	No
Secondary	Health-related Quality of Life (QoL) Assessed With the St. George Respiratory Questionnaire (SGRQ) at Week 52	The SGRQ contained 51 patient-rated items divided into three components: Symptoms (respiratory symptoms, their frequency, and severity), Activity (activities that cause or are limited by breathlessness), and Impacts (social functioning and psychological disturbances resulting from airway disease). A total score for the 3 components was calculated and ranged from 0 to 100. Higher values indicate greater impairment of QoL. The analysis included the same covariates as the primary Outcome Measure.	Week 52	No
Secondary	Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)	Time to first moderate or severe COPD exacerbation was calculated as the number of days from baseline to the day on which the patient experienced the first moderate or severe COPD exacerbation. A COPD exacerbation was considered to be moderate if treatment with systemic corticosteroids and/or antibiotic was required. A COPD exacerbation was considered to be severe if treatment for moderate severity and hospitalization was required.	Baseline to Week 52 (patients with no moderate or severe exacerbations who completed the study were censored at the final visit date, which may have exceeded 52 weeks)	No
Secondary	Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Taken During the Study (Baseline to Week 52)	The number of puffs of rescue medication taken in the previous 12 hours was recorded in the Patient Diary in the morning and evening. The mean daily number of puffs of rescue medication taken was calculated by dividing the number of puffs of rescue medication per day over the 52 weeks of the study by the number of days with non-missing rescue medication data. Rescue medication data recorded during the 14 day run-in period was used to calculate the baseline. The analysis included the same covariates as the primary Outcome Measure. A positive change score indicates more puffs taken.	Baseline to Week 52	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included the same covariates as the primary Outcome Measure.	Day 1, Week 26, and Week 52	No
Secondary	Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52	Trough FVC is defined as the average of the post-dose 23 h 15 min and the 23 h 45 min FVC values. Just prior to FVC measurement, patients performed normal tidal breathing. The patient was given a few breaths warning before being told "At the end of the next normal breath out, take a deep breath all the way in"; they were then verbally encouraged to make a maximal effort before relaxing. The analysis included the same covariates as the primary Outcome Measure.	Day 1, Week 12, Week 26, and Week 52	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.	5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	No
Secondary	Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	Just prior to FVC measurement, patients performed normal tidal breathing. The patient was given a few breaths warning before being told "At the end of the next normal breath out, take a deep breath all the way in"; they were then verbally encouraged to make a maximal effort before relaxing. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.	5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.	5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	No
Secondary	Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	Just prior to FVC measurement, patients performed normal tidal breathing. The patient was given a few breaths warning before being told "At the end of the next normal breath out, take a deep breath all the way in"; they were then verbally encouraged to make a maximal effort before relaxing. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.	5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 3, and 4 hours post-dose. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included the same covariates as the primary Outcome Measure.	From 5 minutes to 4 hours post-dose at Day 1 and Weeks 12, 26, and 52	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose at Day 1 and Weeks 12 and 52	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 3, 4, 6, 8 10, and 12 hours post-dose. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included the same covariates as the primary Outcome Measure.	From 5 minutes to 12 hours post-dose at Day 1 and Weeks 12 and 52	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes and From 12 Hours to 23 Hours 45 Minutes Post-dose at Weeks 12 and 52	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included the same covariates as the primary Outcome Measure.	From 5 minutes to 23 hours 45 minutes post-dose at Weeks 12 and 52	No
Secondary	Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Per Year During the Study (Baseline to Week 52)	The number of moderate or severe exacerbations of COPD per year during the study was calculated by dividing the total number of exacerbations during the study by the total number of years of treatment. A COPD exacerbation was considered to be moderate if treatment with systemic corticosteroids and/or antibiotic was required. A COPD exacerbation was considered to be severe if treatment for moderate severity and hospitalization was required.	Baseline to Week 52	No
Secondary	Percentage of Patients Who Experienced a Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)	A COPD exacerbation was considered to be moderate if treatment with systemic corticosteroids and/or antibiotic was required. A COPD exacerbation was considered to be severe if treatment for moderate severity and hospitalization was required.	Baseline to Week 52	No
Secondary	Percentage of Nights With "no Nighttime Awakenings" During the Study (Baseline to Week 52)	A night with "no nighttime awakenings" was defined as any night where the patient did not wake up due to 1 or more of 6 symptoms (respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and breathlessness). Symptoms occurring during the previous 12 hours were recorded each morning and evening by the patient in an electronic diary. The percentage of nights with 'no nighttime awakenings' was calculated as the total number of nights with "no nighttime awakenings" over the 52 week treatment period divided by the total number of nights where diary recordings were made.	Baseline to Week 52	No
Secondary	Percentage of Days With "no Daytime Symptoms" During the Study (Baseline to Week 52)	A day with "no daytime symptoms" was defined as any day where the patient recorded no cough, no wheeze, no production of sputum, no feeling of breathlessness (other than when running), and no puffs of rescue medication during the previous 12 hours in evening entry in the electronic patient diary. The percentage of days with "no daytime symptoms" was calculated as the total number of days with "no daytime symptoms" over the 52 week treatment period divided by the total number of days where diary recordings were made.	Baseline to Week 52	No
Secondary	Percentage of "Days Able to Perform Usual Daily Activities" During the Study (Baseline to Week 52)	A "day able to perform usual daily activities" was defined as any day where the patient recorded in their electronic diary in the evening that they were not prevented from performing their usual daily activities due to respiratory symptoms during the previous 12 hours. The percentage of "days able to perform usual daily activities" was calculated as the total number of "days able to perform usual daily activities" over the 52 week treatment period divided by the total number of days where diary recordings were made.	Baseline to Week 52	No
Secondary	Change From Baseline in the Mean Daily Total Symptom Score During the Study (Baseline to Week 52)	The daily total symptom score was defined as the sum of the morning and evening patient self-reported diary assessments of 6 symptoms (respiratory symptoms/impact on daily activities, cough, wheeze, amount of sputum, color of sputum, and breathlessness). Means for baseline (14 day maximum run-in period) and the 52 week treatment period were calculated. Mean scores ranged from 0-18, with a higher score indicating worse symptoms. A negative change score indicated improvement.	Baseline to Week 52	No