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GLOW2: 1-year Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Chronic Obstructive Pulmonary Disease (COPD)

Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00929110
Collaborator
(none)
1,066
Enrollment
139
Locations
3
Arms
22
Duration (Months)
7.7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Glycopyrronium bromide
  • Drug: Placebo to glycopyrronium bromide
  • Drug: Tiotropium
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1066 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Apr 1, 2011
Actual Study Completion Date :
Apr 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Glycopyrronium bromide 50 μg

Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Glycopyrronium bromide
Glycopyrronium bromide was supplied in powder-filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
Other Names:
  • NVA237

    		•
    Placebo Comparator: Placebo to glycopyrronium bromide

    Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

    Drug: Placebo to glycopyrronium bromide
    Placebo to glycopyrronium bromide was supplied in powder-filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
    Active Comparator: Tiotropium 18 μg

    Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

    Drug: Tiotropium
    Tiotropium was supplied in powder-filled capsules together with the Handihaler® device.

    Outcome Measures

    Primary Outcome Measures

    1. Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 [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 β2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.

    Secondary Outcome Measures

    1. Transition Dyspnea Index (TDI) at Week 26 [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.

    2. Health-related Quality of Life (QoL) Assessed With the St. George Respiratory Questionnaire (SGRQ) at Week 52 [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.

    3. Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52) [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)]

      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.

    4. Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Taken During the Study (Baseline to Week 52) [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.

    5. Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52 [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.

    6. Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52 [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.

    7. 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 [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.

    8. 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 [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.

    9. 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 [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]

      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.

    10. 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 [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]

      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.

    11. 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 [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.

    12. 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 [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.

    13. 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 [From 5 minutes 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.

    14. Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Per Year During the Study (Baseline to Week 52) [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.

    15. Percentage of Patients Who Experienced a Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52) [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.

    16. Percentage of Nights With "no Nighttime Awakenings" During the Study (Baseline to Week 52) [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.

    17. Percentage of Days With "no Daytime Symptoms" During the Study (Baseline to Week 52) [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.

    18. Percentage of "Days Able to Perform Usual Daily Activities" During the Study (Baseline to Week 52) [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.

    19. Change From Baseline in the Mean Daily Total Symptom Score During the Study (Baseline to Week 52) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Birmingham Alabama United States 35249
    2 Novartis Investigative Site Mobile Alabama United States 36608
    3 Novartis Investigative Site Montgomery Alabama United States 36117
    4 Novartis Investigator Site Fort Smith Arkansas United States 72901
    5 Novartis Investigator Site Anaheim California United States 92801
    6 Novartis Investigative Site Fullerton California United States 92835
    7 Novartis Investigative Site Lakewood California United States 90712-151
    8 Novartis Investigator Site Los Angeles California United States 90025
    9 Novartis Investigator Site Los Angeles California United States 90048
    10 Novartis Investigator Site Mission Viejo California United States 92691
    11 Novartis Investigator Site Paramount California United States 90723
    12 Novartis Investigator Site Riverside California United States 92506
    13 Novartis Investigative Site Rolling Hills Estates California United States 90274
    14 Novartis Investigator Site San Diego California United States 92120
    15 Novartis Investigator Site Colorado Springs Colorado United States 80907
    16 Novartis Investigative site DeLand Florida United States 32720
    17 Novartis Investigative Site Ft. Lauderdale Florida United States 33316-192
    18 Novartis Investigative Site Miami Beach Florida United States 33140
    19 Novartis Investigative Site Miami Florida United States 33186
    20 Novartis Investigative Site Ocala Florida United States 34471
    21 Novartis Investigative Site Panama City Florida United States 32405
    22 Novartis Investigative Site Tampa Florida United States 33606
    23 Novartis Investigator Site Winter Park Florida United States 32789
    24 Novartis Investigative Site Atlanta Georgia United States 30322
    25 Novartis Investigative Site Blue Ridge Georgia United States 30513
    26 Novartis Investigative Site Duluth Georgia United States 30096
    27 Novartis Investigator Site Coeur D'Alene Idaho United States 83814
    28 Novartis Investigator Site Skokie Illinois United States 60076
    29 Novartis Investigator Site New Albany Indiana United States 47150-3054
    30 Novartis Investigator Site Valparaiso Indiana United States 46383
    31 Novartis Investigator Site Council Bluffs Iowa United States 51503-4658
    32 Novartis Investigator Site Iowa City Iowa United States 52240
    33 Novartis Investigator Site Shawnee Kansas United States 66216-1800
    34 Novartis Investigative Center Crescent Springs Kentucky United States 41017
    35 Novartis Investigative Site Crestview Hills Kentucky United States 41017-542
    36 Novartis Investigative Site Hazard Kentucky United States 41701
    37 Novartis Investigative Site Louisville Kentucky United States 40215
    38 Novartis Investigator Site Lafayette Louisiana United States 70508
    39 Novartis Investigator Site Sunset Louisiana United States 70584
    40 Novartis Investigator Site Boys Town Maine United States 68010
    41 Novartis Investigative Site Columbia Maryland United States 21044
    42 Novartis Investigative Site Wheaton Maryland United States 20902
    43 Novartis Investigative Site North Dartmouth Massachusetts United States 02747
    44 Novartis Investigative Site Taunton Massachusetts United States 02780
    45 Novartis Investigator Site Minneapolis Minnesota United States 55402
    46 Novartis Investigator Site St. Louis Missouri United States 63122
    47 Novartis Investigator Site Bozeman Montana United States 59718
    48 Novartis Investigator Site Lincoln Nebraska United States 68510
    49 Novartis Investigator Site Omaha Nebraska United States 68131-2197
    50 Novartis Investigator Site Papillion Nebraska United States 68046
    51 Novartis Investigative Site Skillman New Jersey United States 08558
    52 Novartis Investigative Site Endwell New York United States 13760
    53 Novartis Investigative site Charlotte North Carolina United States 28207
    54 Novartis Investigator Site Cincinnati Ohio United States 45245
    55 Novartis Investigator Site Sylvania Ohio United States 43560
    56 Novartis Investigator Site Toledo Ohio United States 43614
    57 Novartis Investigator Site Oklahoma City Oklahoma United States 73103
    58 Novartis Investigator Site Oklahoma City Oklahoma United States 73112
    59 Novartis Investigator Site Medford Oregon United States 97504-8741
    60 Novartis Investigator Site Medford Oregon United States 97504
    61 Novartis Investigator Site Portland Oregon United States 92713
    62 Novartis Investigator Site Portland Oregon United States 97213
    63 Novartis Investigative Site Downingtown Pennsylvania United States 19335-2620
    64 Novartis Investigative Site Philadelphia Pennsylvania United States 19115
    65 Novartis Investigative Site East Providence Rhode Island United States 02914
    66 Novartis Investigative Site Providence Rhode Island United States 02906
    67 Novartis Investigative Site North Charleston South Carolina United States 29406
    68 Novartis Investigator Site Austin Texas United States 78750
    69 Novartis Investigator Site El Paso Texas United States 79902
    70 Novartis Investigator Site New Braunfels Texas United States 78130-6113
    71 Novartis Investigator Site San Antonio Texas United States 78229
    72 Novartis Investigator Site Provo Utah United States 84604-1584
    73 Novartis Investigative Site Charlottesville Virginia United States 22908
    74 Novartis Investigator Site Tacoma Washington United States 98405-4266
    75 Novartis Investigator Site Milwaukee Wisconsin United States 53209
    76 Novartis Investigative Site Buenos Aires Argentina
    77 Novartis Investigative Site Capital Federal Argentina
    78 Novartis Investigative Site La Plata - Bueno Aire Argentina
    79 Novartis Investigative Site Parana Entre Rios Argentina
    80 Novartis Investigative Site Rosario Argentina
    81 Novartis Investigative Site Tucuman Argentina
    82 Novartis Investigator Site Brampton Canada
    83 Novartis Investigator Site Calgary Canada
    84 Novartis Investigator Site Edmonton Canada
    85 Novartis Investigator Site Kelowna Canada
    86 Novartis Investigator Site Langley Canada
    87 Novartis Investigator Site Niagara Falls Canada
    88 Novartis Investigator Site Quebec Canada
    89 Novartis Investigator Site Ste-Foy Canada
    90 Novartis Investigative Site Santiago Chile
    91 Novartis Investigative Site Talcahuano Chile
    92 Novartis Investigative Site Vina del Mar Chile
    93 Novartis Investigative Site Dijon France
    94 Novartis Investigative Site Paris France
    95 Novartis Investigative Site Rennes Cedex France
    96 Novartis Investigative Site Berlin Germany
    97 Novartis Investigative Site Landsberg Germany
    98 Novartis Investigative Site Muenchen Germany
    99 Novartis Investigative Site Munich Germany
    100 Novartis Investigative Site Gyonsyos Hungary
    101 Novartis Investigative Site Siokok Hungary
    102 Novartis Investigative Site Be'er Sheva Israel
    103 Novartis Investigative Site Haifa Israel
    104 Novartis Investigative Site Jerusalem Israel
    105 Novartis Investigative Site Kfar Saba Israel
    106 Novartis Investigative Site Rehovot Israel
    107 Novartis Investigative Site Firenze Italy
    108 Novartis Investigative Site Monza Italy
    109 Novartis Investigative Site Parma Italy
    110 Novartis Investigative Site Busan Korea, Republic of
    111 Novartis Investigative Site Gyeonggi-go Korea, Republic of
    112 Novartis Investigative Site Incheon Korea, Republic of
    113 Novartis Investigative Site Seoul Korea, Republic of
    114 Novartis Investigative Site Guadalajara Mexico
    115 Novartis Investigative Site Monterrey Mexico
    116 Novartis Investigative Site San Luis Potosi Mexico
    117 Novartis Investigative Site Sneek Netherlands
    118 Novartis Investigator Site Auckland New Zealand
    119 Novartis Investigator Site Christchurch New Zealand
    120 Novartis Investigator Site Hamilton New Zealand
    121 Novartis Investigator Site Tauranga New Zealand
    122 Novartis Investigator Site Wellington New Zealand
    123 Novartis Investigative Site Lima Peru
    124 Novartis Investigative Site Santiago de Surco Peru
    125 Novartis Investigative Site Bialystok Poland
    126 Novartis Investigative Site Bydgoszcz Poland
    127 Novartis Investigative Site Bystra Poland
    128 Novartis Investigative Site Gdansk Poland
    129 Novartis Investigative Site Krakow Poland
    130 Novartis Investigative Site Ostrow Wielkopolski Poland
    131 Novartis Investigative Site Piekary Slaskic Poland
    132 Novartis Investigative Site Tarnow Poland
    133 Novartis Investigative Site Warszawa Poland
    134 Novartis Investigative Site Barnaul Russian Federation
    135 Novartis Investigative Site Irkutsk Russian Federation
    136 Novartis Investigative Site Moscow Russian Federation
    137 Novartis Investigative Site Smolensk Russian Federation
    138 Novartis Investigative Site Volgograd Russian Federation
    139 Novartis Investigative Site Yaroslavl Russian Federation

    Sponsors and Collaborators

    • Novartis

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis
    ClinicalTrials.gov Identifier:
    NCT00929110
    Other Study ID Numbers:
    • CNVA237A2303
    • 2008-008394-63
    First Posted:
    Jun 26, 2009
    Last Update Posted:
    Aug 17, 2012
    Last Verified:
    Aug 1, 2012
    Keywords provided by Novartis
    COPD
    NVA237
    glycopyrronium bromide
    Additional relevant MeSH terms:
    Lung Diseases
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive
    Glycopyrrolate
    Bromides
    Tiotropium Bromide

    Study Results

    Participant Flow

    Recruitment Details A total of 1993 patients were screened from 180 participating sites, of whom 1066 were randomized to 1 of the 3 treatment groups in a 2:1:1 ratio glycopyrronium bromide:placebo:tiotropium.
    Pre-assignment Detail
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Period Title: Overall Study
    STARTED 529 269 268
    COMPLETED 411 193 206
    NOT COMPLETED 118 76 62

    Baseline Characteristics

    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg Total
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Total of all reporting groups
    Overall Participants 525 268 267 1060
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.5
    (9.05)
    63.6
    (9.14)
    63.9
    (8.25)
    63.6
    (8.87)
    Sex: Female, Male (Count of Participants)
    Female
    186
    35.4%
    95
    35.4%
    99
    37.1%
    380
    35.8%
    Male
    339
    64.6%
    173
    64.6%
    168
    62.9%
    680
    64.2%

    Outcome Measures

    1. Primary Outcome
    Title Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
    Description 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 β2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 513 245 253
    Least Squares Mean (Standard Error) [Liters]
    1.469
    (0.0141)
    1.372
    (0.0173)
    1.455
    (0.0170)
    2. Secondary Outcome
    Title Transition Dyspnea Index (TDI) at Week 26
    Description 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.
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 470 217 238
    Least Squares Mean (Standard Error) [Units on a scale]
    2.13
    (0.240)
    1.32
    (0.289)
    2.26
    (0.281)
    3. Secondary Outcome
    Title Health-related Quality of Life (QoL) Assessed With the St. George Respiratory Questionnaire (SGRQ) at Week 52
    Description 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.
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 499 248 251
    Least Squares Mean (Standard Error) [Units on a scale]
    40.85
    (0.854)
    44.16
    (1.040)
    41.32
    (1.024)
    4. Secondary Outcome
    Title Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)
    Description 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.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 525 268 267
    Median (Full Range) [Days]
    363.0
    231.0
    364.0
    5. Secondary Outcome
    Title Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Taken During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 523 263 263
    Least Squares Mean (Standard Error) [Puffs]
    -1.58
    (0.151)
    -1.20
    (0.184)
    -1.83
    (0.183)
    6. Secondary Outcome
    Title Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52
    Description 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.
    Time Frame Day 1, Week 26, and Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 500 250 245
    Day 1
    1.478
    (0.0088)
    1.388
    (0.0109)
    1.471
    (0.0109)
    Week 26 (n=451, 219, 233)
    1.458
    (0.0161)
    1.324
    (0.0196)
    1.408
    (0.0191)
    Week 52 (n=416, 196, 210)
    1.412
    (0.0157)
    1.303
    (0.0198)
    1.392
    (0.0191)
    7. Secondary Outcome
    Title Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52
    Description 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.
    Time Frame Day 1, Week 12, Week 26, and Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 500 250 245
    Day 1
    2.936
    (0.0165)
    2.757
    (0.0205)
    2.930
    (0.0206)
    Week 12 (n=442, 204, 217)
    2.985
    (0.0265)
    2.802
    (0.0329)
    2.970
    (0.0323)
    Week 26 (n=418, 196, 208)
    2.962
    (0.0299)
    2.758
    (0.0361)
    2.892
    (0.0355)
    Week 52 (n=395, 186, 201)
    2.866
    (0.0335)
    2.687
    (0.0399)
    2.866
    (0.0383)
    8. Secondary Outcome
    Title 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
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 144 79 76
    Day 1, minute 5 (n=135, 74, 74)
    1.494
    (0.0135)
    1.416
    (0.0166)
    1.447
    (0.0164)
    Day 1, minute 15 (n=139, 75, 74)
    1.548
    (0.0152)
    1.428
    (0.0185)
    1.485
    (0.0185)
    Day 1, minute 30 (n=143, 77, 74)
    1.561
    (0.0180)
    1.409
    (0.0218)
    1.483
    (0.0219)
    Day 1, hour 1 (n=144, 76, 75)
    1.583
    (0.0172)
    1.404
    (0.0213)
    1.514
    (0.0212)
    Day 1, hour 2 (n=144, 75, 75)
    1.639
    (0.0202)
    1.445
    (0.0248)
    1.569
    (0.0247)
    Day 1, hour 3 (n=143, 74, 73)
    1.629
    (0.0199)
    1.435
    (0.0249)
    1.587
    (0.0248)
    Day 1, hour 4 (n=144, 70, 74)
    1.599
    (0.0221)
    1.415
    (0.0281)
    1.560
    (0.0275)
    Day 1, hour 6 (n=142, 71, 74)
    1.578
    (0.0204)
    1.426
    (0.0255)
    1.575
    (0.0252)
    Day 1, hour 8 (n=137, 70, 75)
    1.544
    (0.0226)
    1.431
    (0.0284)
    1.545
    (0.0278)
    Day1, hour 10 (n=134, 72, 75)
    1.546
    (0.0235)
    1.415
    (0.0290)
    1.537
    (0.0286)
    Day 1, hour 12 (n=130, 69, 70)
    1.522
    (0.0254)
    1.369
    (0.0307)
    1.480
    (0.0306)
    Day 1, hour 23, minute 15 (n=129, 71, 72)
    1.471
    (0.0214)
    1.396
    (0.0259)
    1.481
    (0.0255)
    Day 1, hour 23, minute 45 (n=128, 74, 75)
    1.518
    (0.0210)
    1.446
    (0.0252)
    1.499
    (0.0249)
    Day 15, minute 5 (n=135, 65, 73)
    1.494
    (0.0246)
    1.421
    (0.0315)
    1.490
    (0.0299)
    Day 15, minute 15 (n=133, 70, 72)
    1.530
    (0.0246)
    1.411
    (0.0307)
    1.537
    (0.0303)
    Day 15, minute 30 (n= 139, 70, 74)
    1.551
    (0.0236)
    1.417
    (0.0297)
    1.516
    (0.0289)
    Day 15, hour 1 (n=140, 68, 74)
    1.575
    (0.0242)
    1.409
    (0.0305)
    1.540
    (0.0296)
    Week 5, minute 5 (n=134, 66, 68)
    1.550
    (0.0247)
    1.448
    (0.0319)
    1.525
    (0.0305)
    Week 5, minute 15 (n=136, 67, 70)
    1.575
    (0.0239)
    1.452
    (0.0305)
    1.543
    (0.0295)
    Week 5, minute 30 (n=135, 67, 70)
    1.630
    (0.0260)
    1.481
    (0.0327)
    1.584
    (0.0317)
    Week 9, minute 5 (n=128, 66, 70)
    1.562
    (0.0268)
    1.417
    (0.0341)
    1.520
    (0.0326)
    Week 9, minute 15 (n=130, 66, 71)
    1.583
    (0.0267)
    1.441
    (0.0340)
    1.534
    (0.0326)
    Week 9, minute 30 (n=130, 67, 71)
    1.603
    (0.0265)
    1.427
    (0.0335)
    1.549
    (0.0323)
    Week 12, minute 5 (n=130, 69, 70)
    1.497
    (0.0254)
    1.385
    (0.0319)
    1.474
    (0.0315)
    Week 12, minute 15 (n=129, 67, 66)
    1.523
    (0.0251)
    1.373
    (0.0317)
    1.481
    (0.0315)
    Week 12, minute 30 (n=133, 69, 67)
    1.517
    (0.0275)
    1.362
    (0.0336)
    1.488
    (0.0335)
    Week 12, hour 1 (n=132, 67, 69)
    1.557
    (0.0273)
    1.369
    (0.0341)
    1.519
    (0.0333)
    Week 12, hour 2 (n=129, 65, 68)
    1.596
    (0.0290)
    1.434
    (0.0365)
    1.565
    (0.0353)
    Week 12, hour 3 (n=126, 64, 69)
    1.600
    (0.0291)
    1.443
    (0.0375)
    1.566
    (0.0353)
    Week 12, hour 4 (n=124, 64, 68)
    1.584
    (0.0319)
    1.442
    (0.0407)
    1.535
    (0.0383)
    Week 12, hour 6 (n=123, 63, 69)
    1.558
    (0.0321)
    1.443
    (0.0407)
    1.520
    (0.0381)
    Week 12, hour 8 (n=121, 64, 69)
    1.535
    (0.0310)
    1.408
    (0.0385)
    1.479
    (0.0374)
    Week 12, hour 10 (n=124, 61, 69)
    1.541
    (0.0296)
    1.435
    (0.0392)
    1.532
    (0.0365)
    Week 12, hour 12 (n=122, 58, 68)
    1.522
    (0.0313)
    1.422
    (0.0417)
    1.487
    (0.0382)
    Week 12, hour 16 (n=109, 56, 57)
    1.431
    (0.0320)
    1.360
    (0.0425)
    1.378
    (0.0404)
    Week 12, hour 22 (n=117, 60, 63)
    1.420
    (0.0268)
    1.349
    (0.0350)
    1.371
    (0.0333)
    Week 12, hour 23, minute 15 (n=126, 66, 67)
    1.518
    (0.0269)
    1.456
    (0.0345)
    1.520
    (0.0335)
    Week 12, hour 23, minute 45 (n=124, 65, 63)
    1.513
    (0.0294)
    1.470
    (0.0377)
    1.488
    (0.0374)
    Week 16, minute 5 (n=123, 65, 64)
    1.538
    (0.0296)
    1.430
    (0.0362)
    1.515
    (0.0359)
    Week 16, minute 15 (n=124, 65, 65)
    1.557
    (0.0309)
    1.422
    (0.0380)
    1.530
    (0.0377)
    Week 16, minute 30 (n=125, 65, 65)
    1.570
    (0.0303)
    1.409
    (0.0370)
    1.535
    (0.0368)
    Week 20, minute 5 (n=125, 66, 63)
    1.518
    (0.0281)
    1.393
    (0.0348)
    1.453
    (0.0351)
    Week 20, minute 15 (n=124, 65, 63)
    1.535
    (0.0285)
    1.380
    (0.0354)
    1.479
    (0.0356)
    Week 20, minute 30 (n=125, 65, 63)
    1.576
    (0.0277)
    1.391
    (0.0349)
    1.502
    (0.0350)
    Week 26, minute 5 (n=123, 62, 64)
    1.483
    (0.0278)
    1.361
    (0.0368)
    1.415
    (0.0352)
    Week 26, minute 15 (n=121, 61, 61)
    1.521
    (0.0280)
    1.377
    (0.0373)
    1.464
    (0.0358)
    Week 26, minute 30 (n=125, 64, 64)
    1.529
    (0.0285)
    1.353
    (0.0372)
    1.439
    (0.0359)
    Week 26, hour 1 (n=127, 64, 64)
    1.546
    (0.0275)
    1.364
    (0.0359)
    1.462
    (0.0349)
    Week 26, hour 2 (n=124, 64, 63)
    1.590
    (0.0317)
    1.422
    (0.0403)
    1.520
    (0.0395)
    Week 26, hour 3 (n=124, 64, 64)
    1.614
    (0.0303)
    1.442
    (0.0391)
    1.555
    (0.0380)
    Week 26, hour 4 (n=124, 64, 62)
    1.577
    (0.0304)
    1.416
    (0.0384)
    1.519
    (0.0377)
    Week 26, hour 23, minute 15 (n=120, 55, 61)
    1.477
    (0.0323)
    1.374
    (0.0422)
    1.416
    (0.0399)
    Week 26, hour 23, minute 45 (n=117, 56, 61)
    1.483
    (0.0296)
    1.401
    (0.0395)
    1.405
    (0.0376)
    Week 34, minute 5 (n=125, 62, 63)
    1.515
    (0.0293)
    1.359
    (0.0385)
    1.407
    (0.0372)
    Week 34, minute 15 (n=123, 62, 63)
    1.529
    (0.0300)
    1.360
    (0.0394)
    1.425
    (0.0379)
    Week 34, minute 30 (n=125, 62, 62)
    1.567
    (0.0302)
    1.353
    (0.0398)
    1.452
    (0.0385)
    Week 34, hour 1 (n=125, 62, 63)
    1.557
    (0.0285)
    1.352
    (0.0376)
    1.472
    (0.0361)
    Week 42, minute 5 (n=119, 61, 58)
    1.512
    (0.0305)
    1.394
    (0.0401)
    1.490
    (0.0394)
    Week 42, minute 15 (n=123, 61, 58)
    1.520
    (0.0305)
    1.412
    (0.0403)
    1.491
    (0.0396)
    Week 42, minute 30 (n=123, 61, 58)
    1.537
    (0.0332)
    1.391
    (0.0431)
    1.517
    (0.0424)
    Week 50, minute 5 (n=120, 60, 57)
    1.490
    (0.0269)
    1.357
    (0.0348)
    1.422
    (0.0341)
    Week 50, minute 15 (n=123, 60, 57)
    1.529
    (0.0285)
    1.375
    (0.0369)
    1.452
    (0.0362)
    Week 50, minute 30 (n=123, 60, 58)
    1.545
    (0.0287)
    1.368
    (0.0375)
    1.470
    (0.0366)
    Week 52, minute 5 (n=124, 60, 57)
    1.456
    (0.0276)
    1.337
    (0.0368)
    1.377
    (0.0359)
    Week 52, minute 15 (n=122, 59, 58)
    1.502
    (0.0282)
    1.380
    (0.0378)
    1.428
    (0.0364)
    Week 52, minute 30 (n=125, 62, 58)
    1.483
    (0.0280)
    1.366
    (0.0370)
    1.407
    (0.0362)
    Week 52, hour 1 (n=125, 62, 57)
    1.525
    (0.0271)
    1.356
    (0.0359)
    1.439
    (0.0352)
    Week 52, hour 2 (n=124, 61, 58)
    1.554
    (0.0295)
    1.418
    (0.0393)
    1.479
    (0.0382)
    Week 52, hour 3 (n=123, 62, 56)
    1.558
    (0.0263)
    1.384
    (0.0349)
    1.487
    (0.0345)
    Week 52, hour 4 (n=121, 60, 55)
    1.535
    (0.0297)
    1.381
    (0.0395)
    1.468
    (0.0390)
    Week 52, hour 6 (n=118, 59, 54)
    1.494
    (0.0294)
    1.370
    (0.0392)
    1.461
    (0.0388)
    Week 52, hour 8 (n=119, 59, 54)
    1.473
    (0.0300)
    1.358
    (0.0398)
    1.418
    (0.0394)
    Week 52, hour 10 (n=119, 59, 55)
    1.478
    (0.0304)
    1.349
    (0.0397)
    1.419
    (0.0391)
    Week 52, hour 12 (n=120, 58, 52)
    1.451
    (0.0334)
    1.369
    (0.0446)
    1.347
    (0.0444)
    Week 52, hour 16 (n=117, 53, 46)
    1.377
    (0.0309)
    1.277
    (0.0422)
    1.329
    (0.0420)
    Week 52, hour 22 (n=118, 60, 52)
    1.391
    (0.0302)
    1.314
    (0.0397)
    1.282
    (0.0396)
    Week 52, hour 23, 15 minutes (n=121, 62, 57)
    1.447
    (0.0287)
    1.362
    (0.0378)
    1.387
    (0.0371)
    Week 52, hour 23, 45 minutes (n=122, 61, 57)
    1.434
    (0.0281)
    1.337
    (0.0372)
    1.359
    (0.0364)
    9. Secondary Outcome
    Title 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
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 144 79 76
    Day 1, minute 5 (n=135, 74, 74)
    3.027
    (0.0304)
    2.826
    (0.0363)
    2.956
    (0.0363)
    Day 1, minute 15 (n=139, 75, 74)
    3.050
    (0.0335)
    2.802
    (0.0403)
    2.991
    (0.0406)
    Day 1, minute 30 (n=143, 77, 74)
    3.055
    (0.0343)
    2.752
    (0.0416)
    2.979
    (0.0422)
    Day 1, hour 1 (n=144, 76, 75)
    3.148
    (0.0377)
    2.791
    (0.0460)
    3.041
    (0.0463)
    Day 1, hour 2 (n=144, 75, 75)
    3.179
    (0.0373)
    2.802
    (0.0460)
    3.049
    (0.0461)
    Day 1, hour 3 (n=143, 74, 73)
    3.190
    (0.0433)
    2.826
    (0.0526)
    3.119
    (0.0531)
    Day 1, hour 4 (n=144, 70, 74)
    3.138
    (0.0414)
    2.783
    (0.0515)
    3.102
    (0.0512)
    Day 1, hour 6 (n=142, 71, 74)
    3.173
    (0.0419)
    2.846
    (0.0514)
    3.148
    (0.0513)
    Day 1, hour 8 (n=137, 70, 75)
    3.071
    (0.0404)
    2.804
    (0.0506)
    3.074
    (0.0498)
    Day1, hour 10 (n=134, 72, 75)
    3.134
    (0.0414)
    2.865
    (0.0514)
    3.119
    (0.0510)
    Day 1, hour 12 (n=130, 69, 70)
    3.030
    (0.0444)
    2.709
    (0.0535)
    3.012
    (0.0537)
    Day 1, hour 23, minute 15 (n=129, 71, 72)
    2.991
    (0.0385)
    2.800
    (0.0478)
    2.988
    (0.0471)
    Day 1, hour 23, minute 45 (n=128, 74, 75)
    3.014
    (0.0364)
    2.817
    (0.0444)
    2.994
    (0.0442)
    Day 15, minute 5 (n=135, 65, 73)
    3.051
    (0.0439)
    2.793
    (0.0553)
    3.014
    (0.0534)
    Day 15, minute 15 (n=133, 70, 72)
    3.103
    (0.0443)
    2.790
    (0.0536)
    3.103
    (0.0536)
    Day 15, minute 30 (n= 139, 70, 74)
    3.134
    (0.0420)
    2.825
    (0.0519)
    3.078
    (0.0513)
    Day 15, hour 1 (n=140, 68, 74)
    3.152
    (0.0434)
    2.770
    (0.0537)
    3.060
    (0.0528)
    Week 5, minute 5 (n=134, 66, 68)
    3.139
    (0.0430)
    2.866
    (0.0551)
    3.071
    (0.0534)
    Week 5, minute 15 (n=136, 67, 70)
    3.165
    (0.0501)
    2.850
    (0.0611)
    3.092
    (0.0602)
    Week 5, minute 30 (n=135, 67, 70)
    3.248
    (0.0540)
    2.884
    (0.0644)
    3.180
    (0.0636)
    Week 9, minute 5 (n=128, 66, 70)
    3.195
    (0.0543)
    2.826
    (0.0644)
    3.097
    (0.0632)
    Week 9, minute 15 (n=130, 66, 71)
    3.167
    (0.0507)
    2.823
    (0.0615)
    3.101
    (0.0603)
    Week 9, minute 30 (n=130, 67, 71)
    3.231
    (0.0567)
    2.821
    (0.0675)
    3.149
    (0.0664)
    Week 12, minute 5 (n=130, 69, 70)
    3.060
    (0.0492)
    2.728
    (0.0596)
    3.023
    (0.0596)
    Week 12, minute 15 (n=129, 67, 66)
    3.081
    (0.0482)
    2.740
    (0.0588)
    3.018
    (0.0593)
    Week 12, minute 30 (n=133, 69, 67)
    3.058
    (0.0479)
    2.696
    (0.0585)
    3.027
    (0.0591)
    Week 12, hour 1 (n=132, 67, 69)
    3.164
    (0.0543)
    2.737
    (0.0663)
    3.098
    (0.0655)
    Week 12, hour 2 (n=129, 65, 68)
    3.190
    (0.0526)
    2.784
    (0.0664)
    3.155
    (0.0649)
    Week 12, hour 3 (n=126, 64, 69)
    3.240
    (0.0569)
    2.864
    (0.0713)
    3.146
    (0.0685)
    Week 12, hour 4 (n=124, 64, 68)
    3.119
    (0.0576)
    2.745
    (0.0714)
    3.084
    (0.0686)
    Week 12, hour 6 (n=123, 63, 69)
    3.158
    (0.0594)
    2.852
    (0.0731)
    3.120
    (0.0700)
    Week 12, hour 8 (n=121, 64, 69)
    3.083
    (0.0534)
    2.760
    (0.0657)
    3.011
    (0.0644)
    Week 12, hour 10 (n=124, 61, 69)
    3.130
    (0.0581)
    2.860
    (0.0722)
    3.117
    (0.0692)
    Week 12, hour 12 (n=122, 58, 68)
    3.072
    (0.0599)
    2.771
    (0.0770)
    3.020
    (0.0722)
    Week 12, hour 16 (n=109, 56, 57)
    2.933
    (0.0645)
    2.701
    (0.0800)
    2.880
    (0.0785)
    Week 12, hour 22 (n=117, 60, 63)
    2.924
    (0.0517)
    2.673
    (0.0647)
    2.870
    (0.0629)
    Week 12, hour 23, minute 15 (n=126, 66, 67)
    3.091
    (0.0548)
    2.862
    (0.0676)
    3.110
    (0.0671)
    Week 12, hour 23, minute 45 (n=124, 65, 63)
    3.055
    (0.0507)
    2.826
    (0.0630)
    3.004
    (0.0638)
    Week 16, minute 5 (n=123, 65, 64)
    3.156
    (0.0608)
    2.864
    (0.0719)
    3.104
    (0.0723)
    Week 16, minute 15 (n=124, 65, 65)
    3.156
    (0.0576)
    2.801
    (0.0695)
    3.082
    (0.0699)
    Week 16, minute 30 (n=125, 65, 65)
    3.198
    (0.0552)
    2.815
    (0.0676)
    3.112
    (0.0679)
    Week 20, minute 5 (n=125, 66, 63)
    3.093
    (0.0526)
    2.781
    (0.0630)
    2.993
    (0.0643)
    Week 20, minute 15 (n=124, 65, 63)
    3.112
    (0.0545)
    2.770
    (0.0655)
    3.029
    (0.0666)
    Week 20, minute 30 (n=125, 65, 63)
    3.157
    (0.0559)
    2.778
    (0.0677)
    3.050
    (0.0688)
    Week 26, minute 5 (n=123, 62, 64)
    2.994
    (0.0528)
    2.700
    (0.0670)
    2.954
    (0.0658)
    Week 26, minute 15 (n=121, 61, 61)
    3.041
    (0.0513)
    2.692
    (0.0652)
    2.976
    (0.0644)
    Week 26, minute 30 (n=125, 64, 64)
    3.054
    (0.0464)
    2.700
    (0.0597)
    2.994
    (0.0589)
    Week 26, hour 1 (n=127, 64, 64)
    3.077
    (0.0520)
    2.678
    (0.0658)
    3.016
    (0.0651)
    Week 26, hour 2 (n=124, 64, 63)
    3.110
    (0.0516)
    2.771
    (0.0655)
    3.080
    (0.0650)
    Week 26, hour 3 (n=124, 64, 64)
    3.210
    (0.0648)
    2.871
    (0.0765)
    3.176
    (0.0762)
    Week 26, hour 4 (n=124, 64, 62)
    3.111
    (0.0551)
    2.791
    (0.0664)
    3.086
    (0.0664)
    Week 26, hour 23, minute 15 (n=120, 55, 61)
    3.056
    (0.0600)
    2.803
    (0.0749)
    2.932
    (0.0721)
    Week 26, hour 23, minute 45 (n=117, 56, 61)
    2.998
    (0.0512)
    2.752
    (0.0667)
    2.895
    (0.0646)
    Week 34, minute 5 (n=125, 62, 63)
    3.023
    (0.0573)
    2.731
    (0.0715)
    2.881
    (0.0706)
    Week 34, minute 15 (n=123, 62, 63)
    3.016
    (0.0553)
    2.731
    (0.0691)
    2.898
    (0.0683)
    Week 34, minute 30 (n=125, 62, 62)
    3.081
    (0.0555)
    2.687
    (0.0715)
    2.971
    (0.0708)
    Week 34, hour 1 (n=125, 62, 63)
    3.072
    (0.0564)
    2.703
    (0.0707)
    2.963
    (0.0699)
    Week 42, minute 5 (n=119, 61, 58)
    3.033
    (0.0583)
    2.716
    (0.0744)
    3.069
    (0.0746)
    Week 42, minute 15 (n=123, 61, 58)
    3.022
    (0.0539)
    2.695
    (0.0706)
    3.065
    (0.0699)
    Week 42, minute 30 (n=123, 61, 58)
    3.057
    (0.0565)
    2.723
    (0.0734)
    3.098
    (0.0734)
    Week 50, minute 5 (n=120, 60, 57)
    3.022
    (0.0596)
    2.731
    (0.0727)
    2.963
    (0.0726)
    Week 50, minute 15 (n=123, 60, 57)
    3.042
    (0.0592)
    2.702
    (0.0726)
    2.937
    (0.0725)
    Week 50, minute 30 (n=123, 60, 58)
    3.094
    (0.0613)
    2.731
    (0.0749)
    2.985
    (0.0747)
    Week 52, minute 5 (n=124, 60, 57)
    2.940
    (0.0551)
    2.645
    (0.0701)
    2.860
    (0.0702)
    Week 52, minute 15 (n=122, 59, 58)
    2.960
    (0.0518)
    2.640
    (0.0675)
    2.935
    (0.0666)
    Week 52, minute 30 (n=125, 62, 58)
    2.939
    (0.0499)
    2.625
    (0.0650)
    2.929
    (0.0652)
    Week 52, hour 1 (n=125, 62, 57)
    3.031
    (0.0564)
    2.617
    (0.0698)
    2.980
    (0.0704)
    Week 52, hour 2 (n=124, 61, 58)
    3.062
    (0.0556)
    2.714
    (0.0689)
    3.021
    (0.0689)
    Week 52, hour 3 (n=123, 62, 56)
    3.108
    (0.0648)
    2.716
    (0.0766)
    3.053
    (0.0779)
    Week 52, hour 4 (n=121, 60, 55)
    3.021
    (0.0585)
    2.694
    (0.0724)
    2.978
    (0.0735)
    Week 52, hour 6 (n=118, 59, 54)
    2.986
    (0.0614)
    2.690
    (0.0770)
    2.982
    (0.0781)
    Week 52, hour 8 (n=119, 59, 54)
    2.961
    (0.0646)
    2.637
    (0.0793)
    2.942
    (0.0805)
    Week 52, hour 10 (n=119, 59, 55)
    3.000
    (0.0701)
    2.687
    (0.0840)
    3.012
    (0.0844)
    Week 52, hour 12 (n=120, 58, 52)
    2.881
    (0.0631)
    2.636
    (0.0831)
    2.849
    (0.0847)
    Week 52, hour 16 (n=117, 53, 46)
    2.857
    (0.0694)
    2.542
    (0.0857)
    2.772
    (0.0873)
    Week 52, hour 22 (n=118, 60, 52)
    2.812
    (0.0670)
    2.604
    (0.0810)
    2.716
    (0.0827)
    Week 52, hour 23, 15 minutes (n=121, 62, 57)
    2.888
    (0.0595)
    2.678
    (0.0751)
    2.852
    (0.0755)
    Week 52, hour 23, 45 minutes (n=122, 61, 57)
    2.855
    (0.0558)
    2.607
    (0.0700)
    2.797
    (0.0702)
    10. Secondary Outcome
    Title 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
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 525 268 267
    Day 1, minute 5 (n=495, 255, 253)
    1.443
    (0.0067)
    1.357
    (0.0081)
    1.402
    (0.0081)
    Day 1, minute 15 (n=502, 255, 254)
    1.501
    (0.0074)
    1.359
    (0.0090)
    1.437
    (0.0090)
    Day 1, minute 30 (n=507, 252, 254)
    1.524
    (0.0103)
    1.357
    (0.0126)
    1.468
    (0.0125)
    Day 1, hour 1 (n=511, 256, 254)
    1.552
    (0.0082)
    1.353
    (0.0101)
    1.484
    (0.0101)
    Day 1, hour 2 (n=513, 253, 252)
    1.612
    (0.0090)
    1.397
    (0.0113)
    1.549
    (0.0112)
    Day 1, hour 3 (n=510, 248, 252)
    1.590
    (0.0088)
    1.389
    (0.0111)
    1.560
    (0.0109)
    Day 1, hour 4 (n=504, 239, 250)
    1.590
    (0.0095)
    1.396
    (0.0121)
    1.549
    (0.0117)
    Day 1, hour 23, minute 15 (n=481, 243, 239)
    1.459
    (0.0093)
    1.364
    (0.0115)
    1.457
    (0.0115)
    Day 1, hour 23, minute 45 (n=474, 239, 232)
    1.482
    (0.0094)
    1.390
    (0.0117)
    1.473
    (0.0118)
    Day 15, minute 5 (n=498, 223, 243)
    1.491
    (0.0123)
    1.368
    (0.0157)
    1.472
    (0.0151)
    Day 15, minute 15 (n=487, 229, 239)
    1.527
    (0.0123)
    1.371
    (0.0154)
    1.514
    (0.0151)
    Day 15, minute 30 (n=503, 233, 242)
    1.538
    (0.0122)
    1.368
    (0.0152)
    1.504
    (0.0150)
    Day 15, hour 1 (n=501, 229, 240)
    1.561
    (0.0121)
    1.379
    (0.0153)
    1.525
    (0.0150)
    Week 5, minute 5 (n=476, 221, 231)
    1.509
    (0.0125)
    1.371
    (0.0161)
    1.488
    (0.0157)
    Week 5, minute 15 (n=479, 222, 234)
    1.538
    (0.0126)
    1.389
    (0.0162)
    1.508
    (0.0157)
    Week 5, minute 30 (n=480, 223, 234)
    1.564
    (0.0129)
    1.396
    (0.0165)
    1.525
    (0.0160)
    Week 9, minute 5 (n=454, 217, 227)
    1.529
    (0.0126)
    1.366
    (0.0159)
    1.499
    (0.0157)
    Week 9, minute 15 (n=459, 220, 225)
    1.550
    (0.0132)
    1.376
    (0.0164)
    1.515
    (0.0163)
    Week 9, minute 30 (n=460, 220, 226)
    1.569
    (0.0125)
    1.378
    (0.0158)
    1.531
    (0.0157)
    Week 12, minute 5 (n=453, 212, 230)
    1.502
    (0.0136)
    1.349
    (0.0173)
    1.477
    (0.0167)
    Week 12, minute 15 (n=448, 205, 222)
    1.527
    (0.0131)
    1.352
    (0.0171)
    1.501
    (0.0166)
    Week 12, minute 30 (n=455, 212, 226)
    1.522
    (0.0139)
    1.352
    (0.0176)
    1.491
    (0.0170)
    Week 12, hour 1 (n=455, 210, 227)
    1.556
    (0.0139)
    1.364
    (0.0178)
    1.528
    (0.0171)
    Week 12, hour 2 (n=446, 207, 225)
    1.595
    (0.0145)
    1.423
    (0.0185)
    1.558
    (0.0178)
    Week 12, hour 3 (n=444, 204, 225)
    1.592
    (0.0145)
    1.414
    (0.0186)
    1.561
    (0.0177)
    Week 12, hour 4 (n=437, 202, 224)
    1.558
    (0.0152)
    1.416
    (0.0193)
    1.534
    (0.0183)
    Week 12, hour 23, minute 15 (n=430, 200, 214)
    1.481
    (0.0143)
    1.381
    (0.0183)
    1.457
    (0.0177)
    Week 12, hour 23, minute 45 (n=426, 195, 205)
    1.493
    (0.0149)
    1.413
    (0.0190)
    1.472
    (0.0187)
    Week 16, minute 5 (n=429, 207, 218)
    1.514
    (0.0151)
    1.373
    (0.0185)
    1.487
    (0.0181)
    Week 16, minute 15 (n=428, 209, 219)
    1.530
    (0.0155)
    1.372
    (0.0189)
    1.491
    (0.0186)
    Week 16, minute 30 (n=433, 209, 220)
    1.546
    (0.0160)
    1.372
    (0.0194)
    1.505
    (0.0190)
    Week 20, minute 5 (n=430, 206, 218)
    1.495
    (0.0159)
    1.351
    (0.0198)
    1.464
    (0.0192)
    Week 20, minute 15 (n=430, 207, 220)
    1.525
    (0.0164)
    1.362
    (0.0203)
    1.495
    (0.0196)
    Week 20, minute 30 (n=431, 207, 221)
    1.544
    (0.0164)
    1.362
    (0.0203)
    1.498
    (0.0195)
    Week 26, minute 5 (421, 202, 213)
    1.479
    (0.0153)
    1.339
    (0.0189)
    1.429
    (0.0185)
    Week 26, minute 15 (n=414, 200, 207)
    1.504
    (0.0155)
    1.340
    (0.0193)
    1.458
    (0.0191)
    Week 26, minute 30 (n=424, 206, 213)
    1.513
    (0.0161)
    1.341
    (0.0196)
    1.451
    (0.0193)
    Week 26, hour 1 (n=425, 206, 212)
    1.541
    (0.0160)
    1.345
    (0.0193)
    1.487
    (0.0190)
    Week 26, hour 2 (n=420, 203, 208)
    1.570
    (0.0176)
    1.388
    (0.0212)
    1.524
    (0.0210)
    Week 26, hour 3 (n=416, 204, 213)
    1.570
    (0.0181)
    1.398
    (0.0216)
    1.526
    (0.0211)
    Week 26, hour 4 (n=416, 203, 208)
    1.547
    (0.0175)
    1.384
    (0.0211)
    1.504
    (0.0208)
    Week 26, hour 23, minute 15 (n=405, 187, 202)
    1.464
    (0.0175)
    1.326
    (0.0217)
    1.415
    (0.0212)
    Week 26, hour 23, minute 45 (n=401, 185, 198)
    1.474
    (0.0175)
    1.354
    (0.0218)
    1.426
    (0.0215)
    Week 34, minute 5 (n=408, 194, 212)
    1.481
    (0.0167)
    1.338
    (0.0210)
    1.422
    (0.0202)
    Week 34, minute 15 (n=407, 191, 214)
    1.508
    (0.0172)
    1.333
    (0.0215)
    1.443
    (0.0206)
    Week 34, minute 30 (n=410, 196, 215)
    1.518
    (0.0172)
    1.331
    (0.0214)
    1.444
    (0.0206)
    Week 34, hour 1 (n=412, 195, 215)
    1.534
    (0.0171)
    1.331
    (0.0213)
    1.464
    (0.0205)
    Week 42, minute 5 (n=398, 189, 199)
    1.489
    (0.0172)
    1.342
    (0.0218)
    1.459
    (0.0213)
    Week 42, minute 15 (n=405, 188, 201)
    1.511
    (0.0171)
    1.344
    (0.0218)
    1.477
    (0.0211)
    Week 42, minute 30 (n=405, 189, 201)
    1.518
    (0.0183)
    1.350
    (0.0229)
    1.496
    (0.0222)
    Week 50, minute 5 (n=386, 185, 199)
    1.454
    (0.0155)
    1.336
    (0.0197)
    1.429
    (0.0190)
    Week 50, minute 15 (n=391, 187, 203)
    1.496
    (0.0156)
    1.341
    (0.0199)
    1.462
    (0.0192)
    Week 50, minute 30 (n=392, 186, 204)
    1.504
    (0.0166)
    1.341
    (0.0210)
    1.475
    (0.0200)
    Week 52, minute 5 (n=401, 188, 197)
    1.436
    (0.0155)
    1.305
    (0.0200)
    1.419
    (0.0195)
    Week 52, minute 15 (n=394, 183, 200)
    1.471
    (0.0159)
    1.323
    (0.0208)
    1.451
    (0.0198)
    Week 52, minute 30 (n=402, 189, 202)
    1.471
    (0.0164)
    1.319
    (0.0209)
    1.451
    (0.0202)
    Week 52, hour 1 (n=404, 190, 201)
    1.499
    (0.0161)
    1.325
    (0.0205)
    1.482
    (0.0198)
    Week 52, hour 2 (n=402, 186, 202)
    1.526
    (0.0177)
    1.363
    (0.0224)
    1.511
    (0.0214)
    Week 52, hour 3 (n=400, 186, 199)
    1.525
    (0.0171)
    1.344
    (0.0215)
    1.509
    (0.0207)
    Week 52, hour 4 (n=397, 184, 199)
    1.504
    (0.0176)
    1.346
    (0.0222)
    1.501
    (0.0213)
    Week 52, hour 23, minute 15 (n=388, 183, 198)
    1.419
    (0.0169)
    1.303
    (0.0215)
    1.397
    (0.0205)
    Week 52, hour 23, minute 45 (n=395, 185, 199)
    1.424
    (0.0165)
    1.320
    (0.0210)
    1.411
    (0.0201)
    11. Secondary Outcome
    Title 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
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 525 268 267
    Day 1, minute 5 (n=495, 255, 253)
    2.915
    (0.0145)
    2.731
    (0.0174)
    2.856
    (0.0174)
    Day 1, minute 15 (n=502, 255, 254)
    2.982
    (0.0164)
    2.719
    (0.0199)
    2.903
    (0.0198)
    Day 1, minute 30 (n=507, 252, 254)
    3.004
    (0.0177)
    2.692
    (0.0219)
    2.937
    (0.0217)
    Day 1, hour 1 (n=511, 256, 254)
    3.074
    (0.0173)
    2.732
    (0.0214)
    2.975
    (0.0213)
    Day 1, hour 2 (n=513, 253, 252)
    3.119
    (0.0182)
    2.762
    (0.0227)
    3.033
    (0.0226)
    Day 1, hour 3 (n=510, 248, 252)
    3.129
    (0.0193)
    2.811
    (0.0243)
    3.073
    (0.0239)
    Day 1, hour 4 (n=504, 239, 250)
    3.076
    (0.0192)
    2.767
    (0.0244)
    3.031
    (0.0237)
    Day 1, hour 23, minute 15 (n=481, 243, 239)
    2.926
    (0.0178)
    2.745
    (0.0220)
    2.923
    (0.0220)
    Day 1, hour 23, minute 45 (n=474, 239, 232)
    2.930
    (0.0178)
    2.749
    (0.0221)
    2.923
    (0.0224)
    Day 15, minute 5 (n=498, 223, 243)
    2.984
    (0.0222)
    2.760
    (0.0282)
    2.980
    (0.0272)
    Day 15, minute 15 (n=487, 229, 239)
    3.016
    (0.0220)
    2.748
    (0.0274)
    3.030
    (0.0270)
    Day 15, minute 30 (n=503, 233, 242)
    3.028
    (0.0212)
    2.756
    (0.0269)
    3.018
    (0.0265)
    Day 15, hour 1 (n=501, 229, 240)
    3.068
    (0.0213)
    2.757
    (0.0271)
    3.023
    (0.0267)
    Week 5, minute 5 (n=476, 221, 231)
    3.004
    (0.0215)
    2.768
    (0.0277)
    3.011
    (0.0270)
    Week 5, minute 15 (n=479, 222, 234)
    3.024
    (0.0234)
    2.771
    (0.0294)
    3.024
    (0.0286)
    Week 5, minute 30 (n=480, 223, 234)
    3.085
    (0.0243)
    2.804
    (0.0305)
    3.063
    (0.0297)
    Week 9, minute 5 (n=454, 217, 227)
    3.047
    (0.0262)
    2.767
    (0.0313)
    3.029
    (0.0309)
    Week 9, minute 15 (n=459, 220, 225)
    3.050
    (0.0257)
    2.764
    (0.0312)
    3.046
    (0.0311)
    Week 9, minute 30 (n=460, 220, 226)
    3.079
    (0.0265)
    2.768
    (0.0322)
    3.079
    (0.0319)
    Week 12, minute 5 (n=453, 212, 230)
    2.991
    (0.0253)
    2.726
    (0.0313)
    2.978
    (0.0304)
    Week 12, minute 15 (n=448, 205, 222)
    3.003
    (0.0252)
    2.735
    (0.0316)
    3.004
    (0.0307)
    Week 12, minute 30 (n=455, 212, 226)
    2.985
    (0.0251)
    2.707
    (0.0314)
    2.987
    (0.0306)
    Week 12, hour 1 (n=455, 210, 227)
    3.062
    (0.0267)
    2.741
    (0.0333)
    3.048
    (0.0322)
    Week 12, hour 2 (n=446, 207, 225)
    3.093
    (0.0266)
    2.801
    (0.0335)
    3.065
    (0.0324)
    Week 12, hour 3 (n=444, 204, 225)
    3.129
    (0.0275)
    2.839
    (0.0346)
    3.096
    (0.0332)
    Week 12, hour 4 (n=437, 202, 224)
    3.050
    (0.0278)
    2.793
    (0.0349)
    3.054
    (0.0333)
    Week 12, hour 23, minute 15 (n=430, 200, 214)
    2.991
    (0.0282)
    2.799
    (0.0349)
    2.985
    (0.0341)
    Week 12, hour 23, minute 45 (n=426, 195, 205)
    2.977
    (0.0268)
    2.799
    (0.0336)
    2.946
    (0.0332)
    Week 16, minute 5 (n=429, 207, 218)
    3.016
    (0.0301)
    2.753
    (0.0362)
    3.009
    (0.0355)
    Week 16, minute 15 (n=428, 209, 219)
    3.029
    (0.0293)
    2.737
    (0.0353)
    3.002
    (0.0348)
    Week 16, minute 30 (n=433, 209, 220)
    3.063
    (0.0298)
    2.747
    (0.0359)
    3.036
    (0.0353)
    Week 20, minute 5 (n=430, 206, 218)
    2.985
    (0.0286)
    2.744
    (0.0349)
    2.966
    (0.0338)
    Week 20, minute 15 (n=430, 207, 220)
    3.020
    (0.0293)
    2.749
    (0.0356)
    2.994
    (0.0345)
    Week 20, minute 30 (n=431, 207, 221)
    3.058
    (0.0309)
    2.774
    (0.0374)
    3.028
    (0.0362)
    Week 26, minute 5 (421, 202, 213)
    2.956
    (0.0289)
    2.733
    (0.0352)
    2.945
    (0.0345)
    Week 26, minute 15 (n=414, 200, 207)
    2.980
    (0.0298)
    2.713
    (0.0363)
    2.959
    (0.0360)
    Week 26, minute 30 (n=424, 206, 213)
    2.983
    (0.0282)
    2.715
    (0.0342)
    2.949
    (0.0337)
    Week 26, hour 1 (n=425, 206, 212)
    3.034
    (0.0293)
    2.721
    (0.0352)
    2.997
    (0.0346)
    Week 26, hour 2 (n=420, 203, 208)
    3.049
    (0.0308)
    2.777
    (0.0370)
    3.036
    (0.0366)
    Week 26, hour 3 (n=416, 204, 213)
    3.097
    (0.0331)
    2.831
    (0.0389)
    3.065
    (0.0381)
    Week 26, hour 4 (n=416, 203, 208)
    3.022
    (0.0312)
    2.776
    (0.0369)
    3.021
    (0.0364)
    Week 26, hour 23, minute 15 (n=405, 187, 202)
    2.971
    (0.0321)
    2.758
    (0.0387)
    2.901
    (0.0379)
    Week 26, hour 23, minute 45 (n=401, 185, 198)
    2.952
    (0.0305)
    2.759
    (0.0373)
    2.883
    (0.0368)
    Week 34, minute 5 (n=408, 194, 212)
    2.967
    (0.0321)
    2.713
    (0.0387)
    2.919
    (0.0374)
    Week 34, minute 15 (n=407, 191, 214)
    2.983
    (0.0327)
    2.718
    (0.0392)
    2.948
    (0.0376)
    Week 34, minute 30 (n=410, 196, 215)
    3.002
    (0.0333)
    2.690
    (0.0400)
    2.947
    (0.0386)
    Week 34, hour 1 (n=412, 195, 215)
    3.014
    (0.0336)
    2.711
    (0.0400)
    2.959
    (0.0385)
    Week 42, minute 5 (n=398, 189, 199)
    2.982
    (0.0344)
    2.727
    (0.0415)
    2.983
    (0.0406)
    Week 42, minute 15 (n=405, 188, 201)
    3.001
    (0.0336)
    2.713
    (0.0410)
    3.001
    (0.0398)
    Week 42, minute 30 (n=405, 189, 201)
    3.016
    (0.0345)
    2.734
    (0.0419)
    3.021
    (0.0408)
    Week 50, minute 5 (n=386, 185, 199)
    2.925
    (0.0328)
    2.729
    (0.0393)
    2.942
    (0.0381)
    Week 50, minute 15 (n=391, 187, 203)
    2.971
    (0.0330)
    2.729
    (0.0398)
    2.962
    (0.0384)
    Week 50, minute 30 (n=392, 186, 204)
    2.999
    (0.0342)
    2.731
    (0.0409)
    2.998
    (0.0394)
    Week 52, minute 5 (n=401, 188, 197)
    2.899
    (0.0309)
    2.673
    (0.0377)
    2.916
    (0.0367)
    Week 52, minute 15 (n=394, 183, 200)
    2.942
    (0.0314)
    2.701
    (0.0389)
    2.969
    (0.0371)
    Week 52, minute 30 (n=402, 189, 202)
    2.923
    (0.0325)
    2.666
    (0.0391)
    2.962
    (0.0378)
    Week 52, hour 1 (n=404, 190, 201)
    2.992
    (0.0339)
    2.696
    (0.0405)
    3.011
    (0.0393)
    Week 52, hour 2 (n=402, 186, 202)
    2.997
    (0.0354)
    2.727
    (0.0421)
    3.005
    (0.0405)
    Week 52, hour 3 (n=400, 186, 199)
    3.029
    (0.0359)
    2.742
    (0.0427)
    3.020
    (0.0413)
    Week 52, hour 4 (n=397, 184, 199)
    2.984
    (0.0359)
    2.725
    (0.0425)
    2.991
    (0.0410)
    Week 52, hour 23, minute 15 (n=388, 183, 198)
    2.866
    (0.0349)
    2.675
    (0.0419)
    2.865
    (0.0402)
    Week 52, hour 23, minute 45 (n=395, 185, 199)
    2.869
    (0.0342)
    2.694
    (0.0406)
    2.868
    (0.0390)
    12. Secondary Outcome
    Title 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
    Description 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.
    Time Frame From 5 minutes to 4 hours post-dose at Day 1 and Weeks 12, 26, and 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 519 266 264
    Day 1
    1.570
    (0.0075)
    1.373
    (0.0092)
    1.514
    (0.0092)
    Week 12 (n=460, 214, 232)
    1.560
    (0.0134)
    1.384
    (0.0170)
    1.531
    (0.0164)
    Week 26 (n=430, 206, 216)
    1.546
    (0.0160)
    1.369
    (0.0194)
    1.495
    (0.0190)
    Week 52 (n=405, 192, 203)
    1.502
    (0.0162)
    1.336
    (0.0203)
    1.487
    (0.0196)
    13. Secondary Outcome
    Title 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
    Description 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.
    Time Frame From 5 minutes to 12 hours post-dose at Day 1 and Weeks 12 and 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 144 77 76
    Day 1
    1.566
    (0.0168)
    1.407
    (0.0207)
    1.534
    (0.0206)
    Week 12 (n=133, 69, 70)
    1.539
    (0.0261)
    1.398
    (0.0324)
    1.505
    (0.0320)
    Week 52 (n=125, 62, 58)
    1.492
    (0.0265)
    1.364
    (0.0352)
    1.424
    (0.0344)
    14. Secondary Outcome
    Title 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
    Description 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.
    Time Frame From 5 minutes to 23 hours 45 minutes post-dose at Weeks 12 and 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 133 69 70
    Week 12
    1.486
    (0.0236)
    1.380
    (0.0298)
    1.459
    (0.0294)
    Week 52 (n=125, 62, 58)
    1.445
    (0.0261)
    1.339
    (0.0346)
    1.379
    (0.0338)
    15. Secondary Outcome
    Title Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Per Year During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 525 268 267
    Number (95% Confidence Interval) [Exacerbations per treatment year]
    0.54
    0.80
    0.62
    16. Secondary Outcome
    Title Percentage of Patients Who Experienced a Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 524 266 266
    Number [Percentage of participants]
    32.8
    6.2%
    40.2
    15%
    30.1
    11.3%
    17. Secondary Outcome
    Title Percentage of Nights With "no Nighttime Awakenings" During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 523 263 262
    Least Squares Mean (Standard Error) [Percentage of nights]
    57.36
    (1.842)
    52.15
    (2.239)
    55.47
    (2.230)
    18. Secondary Outcome
    Title Percentage of Days With "no Daytime Symptoms" During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 522 263 263
    Least Squares Mean (Standard Error) [Percentage of days]
    6.54
    (1.208)
    3.81
    (1.431)
    7.14
    (1.424)
    19. Secondary Outcome
    Title Percentage of "Days Able to Perform Usual Daily Activities" During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 522 263 263
    Least Squares Mean (Standard Error) [Percentage of days]
    38.02
    (1.883)
    36.18
    (2.270)
    38.09
    (2.259)
    20. Secondary Outcome
    Title Change From Baseline in the Mean Daily Total Symptom Score During the Study (Baseline to Week 52)
    Description 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.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    Measure Participants 523 263 263
    Least Squares Mean (Standard Error) [Units on a scale]
    -1.85
    (0.125)
    -1.42
    (0.149)
    -1.87
    (0.149)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Arm/Group Description Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
    All Cause Mortality
    Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 65/525 (12.4%) 43/268 (16%) 40/267 (15%)
    Cardiac disorders
    Acute coronary syndrome 2/525 (0.4%) 0/268 (0%) 0/267 (0%)
    Acute myocardial infarction 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Angina pectoris 1/525 (0.2%) 3/268 (1.1%) 0/267 (0%)
    Atrial fibrillation 4/525 (0.8%) 0/268 (0%) 0/267 (0%)
    Atrial flutter 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Bradycardia 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Cardiac failure 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Cardiac failure acute 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Cardiac failure congestive 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Cardiopulmonary failure 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Cardiovascular insufficiency 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Congestive cardiomyopathy 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Myocardial infarction 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Right ventricular failure 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Supraventricular tachycardia 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Tachyarrhythmia 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Ear and labyrinth disorders
    Vertigo 0/525 (0%) 2/268 (0.7%) 0/267 (0%)
    Eye disorders
    Retinal detachment 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Gastrointestinal disorders
    Abdominal mass 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Abdominal pain 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Colitis 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Colitis ischaemic 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Constipation 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Gastrointestinal haemorrhage 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Haemorrhoids 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Inguinal hernia 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Intestinal obstruction 0/525 (0%) 0/268 (0%) 2/267 (0.7%)
    Nausea 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Pancreatitis acute 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Rectal haemorrhage 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Rectal ulcer haemorrhage 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Subileus 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Vomiting 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    General disorders
    Asthenia 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Impaired healing 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Influenza like illness 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Non-cardiac chest pain 1/525 (0.2%) 0/268 (0%) 3/267 (1.1%)
    Pyrexia 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Ulcer haemorrhage 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Cholecystitis chronic 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Cholelithiasis 2/525 (0.4%) 0/268 (0%) 1/267 (0.4%)
    Infections and infestations
    Bronchitis 3/525 (0.6%) 1/268 (0.4%) 0/267 (0%)
    Cellulitis 1/525 (0.2%) 1/268 (0.4%) 1/267 (0.4%)
    Clostridial infection 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Diverticulitis 2/525 (0.4%) 0/268 (0%) 1/267 (0.4%)
    Gastroenteritis 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Herpes zoster 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Lobar pneumonia 0/525 (0%) 1/268 (0.4%) 2/267 (0.7%)
    Lower respiratory tract infection 2/525 (0.4%) 1/268 (0.4%) 1/267 (0.4%)
    Pneumococcal sepsis 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Pneumonia 7/525 (1.3%) 7/268 (2.6%) 4/267 (1.5%)
    Pneumonia bacterial 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Pseudomonas infection 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Pyothorax 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Sepsis 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Sinusitis 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Upper respiratory tract infection 1/525 (0.2%) 0/268 (0%) 1/267 (0.4%)
    Upper respiratory tract infection bacterial 2/525 (0.4%) 3/268 (1.1%) 2/267 (0.7%)
    Viral infection 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Viral upper respiratory tract infection 0/525 (0%) 0/268 (0%) 2/267 (0.7%)
    Injury, poisoning and procedural complications
    Burns third degree 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Collapse of lung 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Contusion 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Fall 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Heat exhaustion 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hip fracture 2/525 (0.4%) 0/268 (0%) 0/267 (0%)
    Incisional hernia, obstructive 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Injury 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Joint dislocation 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Limb crushing injury 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Lower limb fracture 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Radius fracture 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Rib fracture 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Spinal column injury 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Spinal compression fracture 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Spinal fracture 0/525 (0%) 1/268 (0.4%) 1/267 (0.4%)
    Splenic injury 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Stab wound 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Upper limb fracture 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Wrist fracture 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Metabolism and nutrition disorders
    Dehydration 4/525 (0.8%) 2/268 (0.7%) 0/267 (0%)
    Fluid overload 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Hyperglycaemia 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Hypokalaemia 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hyponatraemia 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/525 (0.2%) 1/268 (0.4%) 1/267 (0.4%)
    Cervical spinal stenosis 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Myositis 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Neck pain 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Osteoarthritis 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Spinal osteoarthritis 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Biliary neoplasm 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Bladder transitional cell carcinoma 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Bronchial carcinoma 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Colon cancer 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Lentigo maligna stage unspecified 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Lung squamous cell carcinoma stage unspecified 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Malignant melanoma 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Polycythaemia vera 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Prostate cancer 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Uterine leiomyoma 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Nervous system disorders
    Carotid artery stenosis 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Cerebrovascular accident 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Convulsion 0/525 (0%) 1/268 (0.4%) 1/267 (0.4%)
    Dizziness 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Epilepsy 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Haemorrhagic stroke 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Syncope 3/525 (0.6%) 1/268 (0.4%) 0/267 (0%)
    Transient ischaemic attack 3/525 (0.6%) 1/268 (0.4%) 0/267 (0%)
    Vertebrobasilar insufficiency 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Psychiatric disorders
    Anxiety disorder 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Depression 0/525 (0%) 1/268 (0.4%) 1/267 (0.4%)
    Mental disorder 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Renal and urinary disorders
    Acute prerenal failure 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Renal failure 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Renal failure acute 1/525 (0.2%) 0/268 (0%) 1/267 (0.4%)
    Renal injury 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/525 (0.2%) 0/268 (0%) 1/267 (0.4%)
    Testicular necrosis 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/525 (0.2%) 0/268 (0%) 1/267 (0.4%)
    Chronic obstructive pulmonary disease 19/525 (3.6%) 16/268 (6%) 13/267 (4.9%)
    Cough 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Dyspnoea 0/525 (0%) 2/268 (0.7%) 0/267 (0%)
    Dyspnoea exertional 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hypercapnia 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hypoxia 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Pneumonia aspiration 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Pneumothorax 2/525 (0.4%) 0/268 (0%) 1/267 (0.4%)
    Productive cough 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Pulmonary congestion 1/525 (0.2%) 1/268 (0.4%) 0/267 (0%)
    Pulmonary embolism 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Pulmonary oedema 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Pulmonary toxicity 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Respiratory arrest 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Respiratory failure 1/525 (0.2%) 4/268 (1.5%) 1/267 (0.4%)
    Skin and subcutaneous tissue disorders
    Angioedema 0/525 (0%) 0/268 (0%) 1/267 (0.4%)
    Vascular disorders
    Aortic aneurysm 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hypertension 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Hypotension 2/525 (0.4%) 0/268 (0%) 0/267 (0%)
    Orthostatic hypotension 1/525 (0.2%) 0/268 (0%) 0/267 (0%)
    Subclavian artery stenosis 0/525 (0%) 1/268 (0.4%) 0/267 (0%)
    Other (Not Including Serious) Adverse Events
    Glycopyrronium Bromide 50 μg Placebo to Glycopyrronium Bromide Tiotropium 18 μg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 305/525 (58.1%) 164/268 (61.2%) 156/267 (58.4%)
    Gastrointestinal disorders
    Diarrhoea 10/525 (1.9%) 6/268 (2.2%) 5/267 (1.9%)
    Dry mouth 16/525 (3%) 5/268 (1.9%) 4/267 (1.5%)
    Gastrooesophageal reflux disease 4/525 (0.8%) 6/268 (2.2%) 3/267 (1.1%)
    Nausea 9/525 (1.7%) 6/268 (2.2%) 4/267 (1.5%)
    General disorders
    Oedema peripheral 9/525 (1.7%) 6/268 (2.2%) 8/267 (3%)
    Infections and infestations
    Bronchitis 19/525 (3.6%) 9/268 (3.4%) 12/267 (4.5%)
    Lower respiratory tract infection 22/525 (4.2%) 9/268 (3.4%) 10/267 (3.7%)
    Nasopharyngitis 47/525 (9%) 15/268 (5.6%) 21/267 (7.9%)
    Sinusitis 28/525 (5.3%) 14/268 (5.2%) 9/267 (3.4%)
    Upper respiratory tract infection 57/525 (10.9%) 33/268 (12.3%) 29/267 (10.9%)
    Upper respiratory tract infection bacterial 28/525 (5.3%) 25/268 (9.3%) 20/267 (7.5%)
    Urinary tract infection 14/525 (2.7%) 8/268 (3%) 16/267 (6%)
    Viral infection 1/525 (0.2%) 6/268 (2.2%) 4/267 (1.5%)
    Viral upper respiratory tract infection 9/525 (1.7%) 13/268 (4.9%) 9/267 (3.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 10/525 (1.9%) 7/268 (2.6%) 7/267 (2.6%)
    Back pain 24/525 (4.6%) 9/268 (3.4%) 12/267 (4.5%)
    Nervous system disorders
    Dizziness 9/525 (1.7%) 6/268 (2.2%) 5/267 (1.9%)
    Headache 25/525 (4.8%) 14/268 (5.2%) 12/267 (4.5%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 180/525 (34.3%) 106/268 (39.6%) 85/267 (31.8%)
    Cough 21/525 (4%) 12/268 (4.5%) 12/267 (4.5%)
    Dyspnoea 14/525 (2.7%) 11/268 (4.1%) 6/267 (2.2%)
    Oropharyngeal pain 6/525 (1.1%) 6/268 (2.2%) 2/267 (0.7%)
    Rhinorrhoea 1/525 (0.2%) 9/268 (3.4%) 4/267 (1.5%)
    Vascular disorders
    Hypertension 20/525 (3.8%) 12/268 (4.5%) 14/267 (5.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862 778-8300
    Email
    Responsible Party:
    Novartis
    ClinicalTrials.gov Identifier:
    NCT00929110
    Other Study ID Numbers:
    • CNVA237A2303
    • 2008-008394-63
    First Posted:
    Jun 26, 2009
    Last Update Posted:
    Aug 17, 2012
    Last Verified:
    Aug 1, 2012