- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01005901
A Study to Assess the Safety, Tolerability and Efficacy of NVA237 Versus Placebo (GLOW 1)
A 26-week Treatment, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of NVA237 in Patients With Chronic Obstructive Pulmonary Disease
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Daw Park SA, Australia
- Novartis Investigative Site
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Nova Scotia
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Bridgewater, Nova Scotia, Canada
- Novartis Investigative Site
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Ontario
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Courtice, Ontario, Canada
- Novartis Investigative Site
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Mississuaga, Ontario, Canada
- Novartis Investigative Site
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North York, Ontario, Canada
- Novartis Investigative Site
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Ottawa, Ontario, Canada
- Novartis Investigative Site
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Toronto, Ontario, Canada
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada
- Novartis Investigative Site
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Asahikawa, Japan
- Novartis Investigative Site
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Hamakita, Japan
- Novartis Investigative Site
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Himeji, Japan
- Novartis Investigative Site
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Hitachi, Japan
- Novartis Investigative Site
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Kishiwada, Japan
- Novartis Investigative Site
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Kyoto, Japan
- Novartis Investigative Site
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Matsue, Japan
- Novartis Investigative Site
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Matsusaka, Japan
- Novartis Investigative Site
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Moriya, Japan
- Novartis Investigative Site
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Naka-gun, Japan
- Novartis Investigative Site
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Obihiro, Japan
- Novartis Investigative Site
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Osaka, Japan
- Novartis Investigative Site
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Ota, Japan
- Novartis Investigative Site
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Otsu, Japan
- Novartis Investigative Site
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Sapporo, Japan
- Novartis Investigative Site
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Takatsuki, Japan
- Novartis Investigative Site
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Tokyo, Japan
- Novartis Investigative Site
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Yabu, Japan
- Novartis Investigative Site
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Yonezawa, Japan
- Novartis Investigative Site
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Daegu, Korea, Republic of
- Novartis Investigative Site
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Pusan, Korea, Republic of
- Novartis Investigative Site
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Seoul, Korea, Republic of
- Novartis Investigative Site
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Almelo, Netherlands
- Novartis Investigative Site
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Eindhoven, Netherlands
- Novartis Investigative Site
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Harderwijk, Netherlands
- Novartis Investigative Site
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Heerlen, Netherlands
- Novartis Investigative Site
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Zutphen, Netherlands
- Novartis Investigative Site
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Bucharest, Romania
- Novartis Investigative Site
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Bucuresti, Romania
- Novartis Investigative Site
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Iasi, Romania
- Novartis Investigative Site
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Timisoara, Romania
- Novartis Investigative Site
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Irkutsk, Russian Federation
- Novartis Investigative Site
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Kazan, Russian Federation
- Novartis Investigative Site
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Krasnodar, Russian Federation
- Novartis Investigative Site
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Moscow, Russian Federation
- Novartis Investigative Site
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N. Novgorod, Russian Federation
- Novartis Investigative Site
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Novosibirsk, Russian Federation
- Novartis Investigative Site
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Sochy, Russian Federation
- Novartis Investigative Site
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Stavropol, Russian Federation
- Novartis Investigative Site
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Yaroslavl, Russian Federation
- Novartis Investigative Site
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Singapore, Singapore
- Novartis Investigative Site
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Alicante, Spain
- Novartis Investigative Site
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Badalona, Spain
- Novartis Investigative Site
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Caceres, Spain
- Novartis Investigative Site
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Canet de Mar, Spain
- Novartis Investigative Site
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Centelles, Spain
- Novartis Investigative Site
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Valencia, Spain
- Novartis Investigative Site
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Altunizade, Turkey
- Novartis Investigative Site
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Aydin, Turkey
- Novartis Investigative Site
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Diyarbakir, Turkey
- Novartis Investigative Site
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Istanbul, Turkey
- Novartis Investigative Site
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Izmir, Turkey
- Novartis Investigative Site
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Kinikli/Denizli, Turkey
- Novartis Investigative Site
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Mersin, Turkey
- Novartis Investigative Site
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Soke/Aydin, Turkey
- Novartis Investigative Site
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Yenisehir/Izmir, Turkey
- Novartis Investigative Site
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Alabama
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Birmingham, Alabama, United States
- Novartis Investigative Site
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Fairhope, Alabama, United States
- Novartis Investigative Site
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Arizona
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Glendale, Arizona, United States
- Novartis Investigative Site
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California
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Los Angeles, California, United States
- Novartis Investigative Site
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Walnut Creek, California, United States
- Novartis Investigative Site
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Delaware
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Newark, Delaware, United States
- Novartis Investigative Site
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Florida
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Port Orange, Florida, United States
- Novartis Investigative Site
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Tamarac, Florida, United States
- Novartis Investigative Site
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Kansas
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Topeka, Kansas, United States
- Novartis Investigative Site
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Kentucky
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Madisonville, Kentucky, United States
- Novartis Investigative Site
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Louisiana
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Slidell, Louisiana, United States
- Novartis Investigative Site
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Maine
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Biddeford, Maine, United States
- Novartis Investigative Site
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Maryland
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Pikesville, Maryland, United States
- Novartis Investigative Site
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Michigan
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Ann Arbor, Michigan, United States
- Novartis Investigative Site
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Livonia, Michigan, United States
- Novartis Investigative Site
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Minnesota
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Minneapolis, Minnesota, United States
- Novartis Investigative Site
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Missouri
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Kansas City, Missouri, United States
- Novartis Investigative Site
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St. Charles, Missouri, United States
- Novartis Investigative Site
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Montana
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Missoula, Montana, United States
- Novartis Investigative Site
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Nebraska
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Bellevue, Nebraska, United States
- Novartis Investigative Site
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Omaha, Nebraska, United States
- Novartis Investigative Site
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Nevada
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Reno, Nevada, United States
- Novartis Investigative Site
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New Jersey
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New Brunswick, New Jersey, United States
- Novartis Investigative Site
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New York
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Rochester, New York, United States
- Novartis Investigative Site
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Ohio
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Cincinnati, Ohio, United States
- Novartis Investigative Site
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Oklahoma
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Oklahoma City, Oklahoma, United States
- Novartis Investigative Site
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Tulsa, Oklahoma, United States
- Novartis Investigative Site
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Rhode Island
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Lincoln, Rhode Island, United States
- Novartis Investigative Site
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Tennessee
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Johnson City, Tennessee, United States
- Novartis Investigative Site
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Texas
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Corpus Christi, Texas, United States
- Novartis Investigative Site
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McKinney, Texas, United States
- Novartis Investigative Site
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San Antonio, Texas, United States
- Novartis Investigative Site
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Virginia
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Richmond, Virginia, United States
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
1. Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008) and:
- Smoking history of at least 10 pack-years
- Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value
- Post-bronchodilator FEV1/FVC (forced vital capacity) < 70%
Exclusion Criteria:
- Patients who have had a lower respiratory tract infection within 6 weeks prior to Visit 1
- Patients with concomitant pulmonary disease
- Patients with a history of asthma
- Any patient with lung cancer or a history of lung cancer
- Patients with a history of certain cardiovascular comorbid conditions
- Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
- Patients in the active phase of a supervised pulmonary rehabilitation program
- Patients contraindicated for tiotropium or ipratropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Glycopyrronium bromide
Glycopyrronium bromide 50µg delivered once daily via Single Dose Dry Powder Inhaler (SDDPI).
At visit 1 all patients were provided with a short acting β2-agonist (salbutamol/albuterol) which they were instructed to use throughout the study as rescue medication.
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Glycopyrronium bromide 50µg was supplied as inhalation capsules for use via a Single Dose Dry Powder Inhaler (SDDPI)
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Placebo Comparator: Placebo
Placebo delivered once daily via SDDPI.
At Visit 1 all patients were provided with a short acting β2-agonist (salbutamol/albuterol) which they were instructed to use throughout the study as rescue medication.
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Placebo inhalation capsules were provided for use via a SDDPI
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Trough Forced Expiratory Volume in 1 Second (FEV1) at 12 Weeks
Time Frame: 12 weeks
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Spirometry was conducted according to internationally accepted standards.
Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings.
Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment
Time Frame: 26 weeks
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Transition Dyspnea Index (TDI) captures changes from baseline.
The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline.
A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
Mixed model used baseline TDI, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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26 weeks
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Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Total Score After 26 Weeks of Treatment
Time Frame: 26 weeks
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SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts.
The lowest possible value is zero and the highest 100.
Higher values correspond to greater impairment in quality of life.
Mixed model used baseline SGRQ, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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26 weeks
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Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During 26 Weeks of Treatment
Time Frame: 26 weeks
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The time to the first moderate or severe COPD exacerbation was the study day on which the patient experienced first moderate or severe COPD exacerbation.
COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required.
COPD exacerbations are considered to be severe if treatment for moderate severity and hospitalization were required.
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26 weeks
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Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Week 26)
Time Frame: 26 weeks
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Participants recorded the number of puffs of rescue medication taken in the previous 12 hours in the morning and evening.
The total number of puffs of rescue medication per day over the full 26 weeks was calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient.
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26 weeks
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FEV1 at Each Time-point on Day 1 and Week 26
Time Frame: Day 1 and Week 26
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Spirometry was conducted according to internationally accepted standards.
FEV1 was measured at all time points up to 4 hours post-dose, and at 23 hours 15 min and 23 hours 45 min, by visit.
Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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Day 1 and Week 26
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Forced Vital Capacity (FVC) at Each Time-point on Day 1 and Week 26
Time Frame: Day 1 and Week 26
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Spirometry was conducted according to internationally accepted standards.
FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 15 min and 23 hours 45 min, by visit.
Mixed model used baseline FVC, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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Day 1 and Week 26
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FEV1 Area Under the Curve (AUC) (5 Min - 12 Hour) at Day 1, Week 12 and Week 26
Time Frame: Day 1, Week 12 and Week 26
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The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 12 h post dose at Week 1 Day 1, Week 12 and Week 26 for every patient in the serial spirometry subgroup.
Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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Day 1, Week 12 and Week 26
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FEV1 Area Under Curve (AUC) (5 Min - 23 Hour 45 Min) at Week 12 and Week 26
Time Frame: Week 12 and Week 26
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The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 23 h 45 min post dose at week12/week 13and week 26/week 27 where available for every patient in the serial spirometry subgroup.
Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
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Week 12 and Week 26
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Trough FEV1 and FVC at Day 1 and Week 26
Time Frame: Day 1 and Week 26
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Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates. Trough FVC was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FVC readings. Mixed model used baseline FVC, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates. |
Day 1 and Week 26
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Change in 24-hourly Mean Heart Rate at Day 1, Week 12 and Week 26
Time Frame: Baseline, Day 1, Week 12 and Week 26
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The mean heart rate was collected with a 24 hour Holter monitor in a sub-set of the safety population.
The change between baseline and day 1, week 12 and week 26 was calculated.
The analysis of the Holter recordings was performed by a central facility.
Data on heart rate, heart rate variability, supraventricular and ventricular ectopy were collected and assessed.
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Baseline, Day 1, Week 12 and Week 26
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Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations
Time Frame: 26 Weeks and 30 Day follow-up
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Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen.
Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
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26 Weeks and 30 Day follow-up
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Rate of Moderate or Severe COPD Exacerbations Over the 26 Week Treatment Period
Time Frame: 26 weeks
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One overall rate is calculated for the entire study population.
Rate is the number of moderate or severe exacerbations per year = total number of moderate or severe exacerbations for all participants/total number of treatment years for all participants.
COPD exacerbations were considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required.
COPD exacerbations were considered to be severe if treatment for moderate severity and hospitalization were required.
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26 weeks
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Percentage of Nights With no Nighttime Awakenings Over the 26 Week Treatment Period
Time Frame: 26 Weeks
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The percentage of nights with no nighttime awakenings is defined as the total number of nights with no nighttime awakenings over the 26 week treatment period divided by the total number of night where diary recordings have been made. Mixed model used baseline nighttime awakenings, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates. |
26 Weeks
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Percentage of Days With no Daytime Symptoms Over the 26 Week Treatment Period
Time Frame: 26 Weeks
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The percentage of days with no daytime symptoms is defined as the total number of days with no daytime symptoms over the 26 week treatment period divided by the total number of days where diary recordings have been made. Mixed model used baseline daytime symptoms, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates. |
26 Weeks
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Percentage of Days Able to Perform Usual Daily Activities Over the 26 Week Treatment Period
Time Frame: 26 Weeks
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The percentage of days able to perform usual daily activities is defined as the total number of days able to perform usual activities over the 26 week treatment period divided by the total number of days where diary recordings have been made. Mixed model used baseline ability to perform usual daily activities, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates. |
26 Weeks
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Mean Daily Total Symptom Score Over the 26 Week Treatment Period
Time Frame: 26 Weeks
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The daily symptom score was calculated as the sum of the worst of the morning and evening assessments for each symptom (symptoms, cough, wheeze, sputum color/production, and breathlessness). The score can range from 0 to 18 with 0 indicating no symptoms. The higher the score, the worse the symptomatic status. A negative change (lower number) indicates improvement. Mixed model used baseline symptom variables, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates. |
26 Weeks
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- D'Urzo A, Ferguson GT, van Noord JA, Hirata K, Martin C, Horton R, Lu Y, Banerji D, Overend T. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respir Res. 2011 Dec 7;12(1):156. doi: 10.1186/1465-9921-12-156.
- D'Urzo A, Kerwin E, Overend T, D'Andrea P, Chen H, Goyal P. Once daily glycopyrronium for the treatment of COPD: pooled analysis of the GLOW1 and GLOW2 studies. Curr Med Res Opin. 2014 Mar;30(3):493-508. doi: 10.1185/03007995.2013.858618. Epub 2013 Nov 19.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Adjuvants, Anesthesia
- Anticonvulsants
- Glycopyrrolate
- Bromides
Other Study ID Numbers
- CNVA237A2304
- 2009-013504-32 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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