GLOW 1: A Study to Assess the Safety, Tolerability and Efficacy of NVA237 Versus Placebo
Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT01005901
Collaborator
(none)
1,324
97
2
14
13.6
1
Study Details
Study Description
Brief Summary
A study to assess the safety, tolerability and efficacy of NVA237 versus placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1324 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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 Start Date
:
Oct 1, 2009
Actual Primary Completion Date
:
Dec 1, 2010
Actual Study Completion Date
:
Dec 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Glycopyrronium bromide
Glycopyrronium bromide 50µg was supplied as inhalation capsules for use via a Single Dose Dry Powder Inhaler (SDDPI)
|
| 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. |
Drug: Placebo
Placebo inhalation capsules were provided for use via a SDDPI
|
Outcome Measures
Primary Outcome Measures
- Trough Forced Expiratory Volume in 1 Second (FEV1) at 12 Weeks [12 weeks]
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.
Secondary Outcome Measures
- Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment [26 weeks]
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.
- Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Total Score After 26 Weeks of Treatment [26 weeks]
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.
- Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During 26 Weeks of Treatment [26 weeks]
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.
- Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Week 26) [26 weeks]
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.
- FEV1 at Each Time-point on Day 1 and Week 26 [Day 1 and Week 26]
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.
- Forced Vital Capacity (FVC) at Each Time-point on Day 1 and Week 26 [Day 1 and Week 26]
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.
- FEV1 Area Under the Curve (AUC) (5 Min - 12 Hour) at Day 1, Week 12 and Week 26 [Day 1, Week 12 and Week 26]
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.
- FEV1 Area Under Curve (AUC) (5 Min - 23 Hour 45 Min) at Week 12 and Week 26 [Week 12 and Week 26]
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.
- Trough FEV1 and FVC at Day 1 and Week 26 [Day 1 and Week 26]
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.
- Change in 24-hourly Mean Heart Rate at Day 1, Week 12 and Week 26 [Baseline, Day 1, Week 12 and Week 26]
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.
- Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations [26 Weeks and 30 Day follow-up]
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.
- Rate of Moderate or Severe COPD Exacerbations Over the 26 Week Treatment Period [26 weeks]
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.
- Percentage of Nights With no Nighttime Awakenings Over the 26 Week Treatment Period [26 Weeks]
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.
- Percentage of Days With no Daytime Symptoms Over the 26 Week Treatment Period [26 Weeks]
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.
- Percentage of Days Able to Perform Usual Daily Activities Over the 26 Week Treatment Period [26 Weeks]
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.
- Mean Daily Total Symptom Score Over the 26 Week Treatment Period [26 Weeks]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Birmingham | Alabama | United States | |
| 2 | Novartis Investigative Site | Fairhope | Alabama | United States | |
| 3 | Novartis Investigative Site | Glendale | Arizona | United States | |
| 4 | Novartis Investigative Site | Los Angeles | California | United States | |
| 5 | Novartis Investigative Site | Walnut Creek | California | United States | |
| 6 | Novartis Investigative Site | Newark | Delaware | United States | |
| 7 | Novartis Investigative Site | Port Orange | Florida | United States | |
| 8 | Novartis Investigative Site | Tamarac | Florida | United States | |
| 9 | Novartis Investigative Site | Topeka | Kansas | United States | |
| 10 | Novartis Investigative Site | Madisonville | Kentucky | United States | |
| 11 | Novartis Investigative Site | Slidell | Louisiana | United States | |
| 12 | Novartis Investigative Site | Biddeford | Maine | United States | |
| 13 | Novartis Investigative Site | Pikesville | Maryland | United States | |
| 14 | Novartis Investigative Site | Ann Arbor | Michigan | United States | |
| 15 | Novartis Investigative Site | Livonia | Michigan | United States | |
| 16 | Novartis Investigative Site | Minneapolis | Minnesota | United States | |
| 17 | Novartis Investigative Site | Kansas City | Missouri | United States | |
| 18 | Novartis Investigative Site | St. Charles | Missouri | United States | |
| 19 | Novartis Investigative Site | Missoula | Montana | United States | |
| 20 | Novartis Investigative Site | Bellevue | Nebraska | United States | |
| 21 | Novartis Investigative Site | Omaha | Nebraska | United States | |
| 22 | Novartis Investigative Site | Reno | Nevada | United States | |
| 23 | Novartis Investigative Site | New Brunswick | New Jersey | United States | |
| 24 | Novartis Investigative Site | Rochester | New York | United States | |
| 25 | Novartis Investigative Site | Cincinnati | Ohio | United States | |
| 26 | Novartis Investigative Site | Oklahoma City | Oklahoma | United States | |
| 27 | Novartis Investigative Site | Tulsa | Oklahoma | United States | |
| 28 | Novartis Investigative Site | Lincoln | Rhode Island | United States | |
| 29 | Novartis Investigative Site | Johnson City | Tennessee | United States | |
| 30 | Novartis Investigative Site | Corpus Christi | Texas | United States | |
| 31 | Novartis Investigative Site | McKinney | Texas | United States | |
| 32 | Novartis Investigative Site | San Antonio | Texas | United States | |
| 33 | Novartis Investigative Site | Richmond | Virginia | United States | |
| 34 | Novartis Investigative Site | Daw Park SA | Australia | ||
| 35 | Novartis Investigative Site | Bridgewater | Nova Scotia | Canada | |
| 36 | Novartis Investigative Site | Courtice | Ontario | Canada | |
| 37 | Novartis Investigative Site | Mississuaga | Ontario | Canada | |
| 38 | Novartis Investigative Site | North York | Ontario | Canada | |
| 39 | Novartis Investigative Site | Ottawa | Ontario | Canada | |
| 40 | Novartis Investigative Site | Toronto | Ontario | Canada | |
| 41 | Novartis Investigative Site | Montreal | Quebec | Canada | |
| 42 | Novartis Investigative Site | Asahikawa | Japan | ||
| 43 | Novartis Investigative Site | Hamakita | Japan | ||
| 44 | Novartis Investigative Site | Himeji | Japan | ||
| 45 | Novartis Investigative Site | Hitachi | Japan | ||
| 46 | Novartis Investigative Site | Kishiwada | Japan | ||
| 47 | Novartis Investigative Site | Kyoto | Japan | ||
| 48 | Novartis Investigative Site | Matsue | Japan | ||
| 49 | Novartis Investigative Site | Matsusaka | Japan | ||
| 50 | Novartis Investigative Site | Moriya | Japan | ||
| 51 | Novartis Investigative Site | Naka-gun | Japan | ||
| 52 | Novartis Investigative Site | Obihiro | Japan | ||
| 53 | Novartis Investigative Site | Osaka | Japan | ||
| 54 | Novartis Investigative Site | Ota | Japan | ||
| 55 | Novartis Investigative Site | Otsu | Japan | ||
| 56 | Novartis Investigative Site | Sapporo | Japan | ||
| 57 | Novartis Investigative Site | Takatsuki | Japan | ||
| 58 | Novartis Investigative Site | Tokyo | Japan | ||
| 59 | Novartis Investigative Site | Yabu | Japan | ||
| 60 | Novartis Investigative Site | Yonezawa | Japan | ||
| 61 | Novartis Investigative Site | Daegu | Korea, Republic of | ||
| 62 | Novartis Investigative Site | Pusan | Korea, Republic of | ||
| 63 | Novartis Investigative site | Seoul | Korea, Republic of | ||
| 64 | Novartis Investigative Site | Almelo | Netherlands | ||
| 65 | Novartis Investigative Site | Eindhoven | Netherlands | ||
| 66 | Novartis Investigative Site | Harderwijk | Netherlands | ||
| 67 | Novartis Investigative Site | Heerlen | Netherlands | ||
| 68 | Novartis Investigative Site | Zutphen | Netherlands | ||
| 69 | Novartis Investigative Site | Bucharest | Romania | ||
| 70 | Novartis Investigative Site | Bucuresti | Romania | ||
| 71 | Novartis Investigative Site | Iasi | Romania | ||
| 72 | Novartis Investigative Site | Timisoara | Romania | ||
| 73 | Novartis Investigative Site | Irkutsk | Russian Federation | ||
| 74 | Novartis Investigative Site | Kazan | Russian Federation | ||
| 75 | Novartis Investigative Site | Krasnodar | Russian Federation | ||
| 76 | Novartis Investigative Site | Moscow | Russian Federation | ||
| 77 | Novartis Investigative Site | N. Novgorod | Russian Federation | ||
| 78 | Novartis Investigative Site | Novosibirsk | Russian Federation | ||
| 79 | Novartis Investigative Site | Sochy | Russian Federation | ||
| 80 | Novartis Investigative Site | Stavropol | Russian Federation | ||
| 81 | Novartis Investigative Site | Yaroslavl | Russian Federation | ||
| 82 | Novartis Investigative Site | Singapore | Singapore | ||
| 83 | Novartis Investigative Site | Alicante | Spain | ||
| 84 | Novartis Investigative Site | Badalona | Spain | ||
| 85 | Novartis Investigative Site | Caceres | Spain | ||
| 86 | Novartis Investigative Site | Canet de Mar | Spain | ||
| 87 | Novartis Investigative Site | Centelles | Spain | ||
| 88 | Novartis Investigative Site | Valencia | Spain | ||
| 89 | Novartis Investigative Site | Altunizade | Turkey | ||
| 90 | Novartis Investigative Site | Aydin | Turkey | ||
| 91 | Novartis Investigative Site | Diyarbakir | Turkey | ||
| 92 | Novartis Investigative Site | Istanbul | Turkey | ||
| 93 | Novartis Investigative Site | Izmir | Turkey | ||
| 94 | Novartis Investigative Site | Kinikli/Denizli | Turkey | ||
| 95 | Novartis Investigative Site | Mersin | Turkey | ||
| 96 | Novartis Investigative Site | Soke/Aydin | Turkey | ||
| 97 | Novartis Investigative Site | Yenisehir/Izmir | Turkey |
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:
NCT01005901
Other Study ID Numbers:
- CNVA237A2304
- 2009-013504-32
First Posted:
Nov 1, 2009
Last Update Posted:
Apr 12, 2012
Last Verified:
Dec 1, 2011
Keywords provided by Novartis
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 1324 participants were screened. 822 participants entered the study. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 552 | 270 |
| Safety Population | 550 | 267 |
| Full Analysis Set | 534 | 260 |
| COMPLETED | 450 | 212 |
| NOT COMPLETED | 102 | 58 |
Baseline Characteristics
| Arm/Group Title | Glycopyrronium Bromide | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 550 | 267 | 817 |
| Age, Customized (participants) [Number] | |||
| <65 years |
278
50.5%
|
134
50.2%
|
412
50.4%
|
| 65 to <75 years |
199
36.2%
|
98
36.7%
|
297
36.4%
|
| >=75 years |
73
13.3%
|
35
13.1%
|
108
13.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
96
17.5%
|
52
19.5%
|
148
18.1%
|
| Male |
454
82.5%
|
215
80.5%
|
669
81.9%
|
Outcome Measures
| Title | Trough Forced Expiratory Volume in 1 Second (FEV1) at 12 Weeks |
|---|---|
| Description | 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. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) The FAS included all randomized patients who received at least one dose of study medication. Patients in this group were analyzed according to the treatment to which they were randomized. Missing trough FEV1 values at week 12 were imputed using LOCF with pre-dose trough FEV1. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 512 | 243 |
| Least Squares Mean (Standard Error) [Liters] |
1.408
(0.0105)
|
1.301
(0.0137)
|
| Title | Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment |
|---|---|
| Description | 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. |
| Time Frame | 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. Patients per treatment group with no missing data were included in this analysis. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 493 | 240 |
| Least Squares Mean (Standard Error) [Units on a scale] |
1.84
(0.257)
|
0.80
(0.294)
|
| Title | Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Total Score After 26 Weeks of Treatment |
|---|---|
| Description | 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. |
| Time Frame | 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. Individual component score was imputed with LOCF (last observation carried forward). |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 502 | 246 |
| Least Squares Mean (Standard Error) [Units on a scale] |
39.50
(0.813)
|
42.31
(0.992)
|
| Title | Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During 26 Weeks of Treatment |
|---|---|
| Description | 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. |
| Time Frame | 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. The median values were not estimable. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 534 | 260 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
| Title | Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Week 26) |
|---|---|
| Description | 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. |
| Time Frame | 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. Patients with observations both at baseline and week 26 were included in this analysis |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 529 | 259 |
| Least Squares Mean (Standard Error) [Puffs per day] |
-1.21
(0.122)
|
-0.75
(0.156)
|
| Title | FEV1 at Each Time-point on Day 1 and Week 26 |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. "n" indicates number of patients with observation at each time-point |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 519 | 253 |
| Day 1: 5 min (n = 497, 240) |
1.388
(0.0057)
|
1.295
(0.0076)
|
| Day 1: 15 min (n = 503, 249) |
1.435
(0.0066)
|
1.292
(0.0087)
|
| Day 1: 30 min (n = 511, 252) |
1.472
(0.0070)
|
1.299
(0.0093)
|
| Day 1: 1 hour (n = 513, 253) |
1.493
(0.0070)
|
1.296
(0.0094)
|
| Day 1: 2 hours (n = 514, 251) |
1.562
(0.0076)
|
1.355
(0.0102)
|
| Day 1: 3 hours (n = 519, 248) |
1.544
(0.0079)
|
1.349
(0.0108)
|
| Day 1: 4 hours (n = 514, 247) |
1.548
(0.0077)
|
1.365
(0.0105)
|
| Day 1: 23 hours 15 min (n = 499, 244) |
1.400
(0.0078)
|
1.289
(0.0103)
|
| Day 1: 23 hours 45 min (n = 498, 244) |
1.428
(0.0083)
|
1.328
(0.0108)
|
| Week 26: pre-dose trough (n = 447, 208) |
1.371
(0.0100)
|
1.256
(0.0140)
|
| Week 26: -45 min (n = 447, 208) |
1.373
(0.0104)
|
1.256
(0.0145)
|
| Week 26: -15 min (n = 443, 205) |
1.368
(0.0104)
|
1.252
(0.0144)
|
| Week 26: 5 min (n = 439, 208) |
1.409
(0.0106)
|
1.255
(0.0147)
|
| Week 26: 15 min (n = 435, 205) |
1.427
(0.0109)
|
1.269
(0.0152)
|
| Week 26: 30 min (n = 440, 207) |
1.433
(0.0112)
|
1.259
(0.0155)
|
| Week 26: 1 hour (n = 438, 206) |
1.459
(0.0115)
|
1.251
(0.0159)
|
| Week 26: 2 hours (n = 438, 203) |
1.508
(0.0114)
|
1.299
(0.0160)
|
| Week 26: 3 hours (n = 439, 204) |
1.504
(0.0124)
|
1.299
(0.0170)
|
| Week 26: 4 hours (n = 438, 205) |
1.489
(0.0114)
|
1.312
(0.0158)
|
| Week 26: 23 hours 15 min (n = 434, 206) |
1.386
(0.0118)
|
1.267
(0.0158)
|
| Week 26: 23 hours 45 min (n = 434, 206) |
1.396
(0.0116)
|
1.282
(0.0157)
|
| Title | Forced Vital Capacity (FVC) at Each Time-point on Day 1 and Week 26 |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. "n" indicates number of patients with observation at each time-point. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 534 | 260 |
| Day 1: 5 min (n = 497, 240) |
2.887
(0.0132)
|
2.675
(0.0173)
|
| Day 1: 15 min (n = 503, 249) |
2.943
(0.0147)
|
2.660
(0.0188)
|
| Day 1: 30 min (n = 511, 252) |
2.948
(0.0155)
|
2.637
(0.0199)
|
| Day 1: 1hour (n = 513, 253) |
3.019
(0.0148)
|
2.669
(0.0198)
|
| Day 1: 2 hours (n = 514, 251) |
3.086
(0.0166)
|
2.754
(0.0219)
|
| Day 1: 3 hours (n = 519, 248) |
3.096
(0.0168)
|
2.783
(0.0227)
|
| Day 1: 4 hours (n = 514, 247) |
3.064
(0.0161)
|
2.760
(0.0217)
|
| Day 1: 23 hours 15 min (n = 499, 244) |
2.895
(0.0169)
|
2.693
(0.0221)
|
| Day 1: 23 hours 45 min (n = 498, 244) |
2.907
(0.0169)
|
2.718
(0.0219)
|
| Week 26: Pre-dose trough (n = 447, 208) |
2.827
(0.0238)
|
2.623
(0.0305)
|
| Week 26: -45 min (n = 447, 208) |
2.859
(0.0271)
|
2.658
(0.0337)
|
| Week 26: -15 min (n = 443, 205) |
2.798
(0.0235)
|
2.589
(0.0306)
|
| Week 26: 5 min (n = 439, 208) |
2.891
(0.0251)
|
2.639
(0.0318)
|
| Week 26: 15 min (n = 435, 205) |
2.895
(0.0240)
|
2.660
(0.0309)
|
| Week 26: 30 min (n = 440, 207) |
2.885
(0.0239)
|
2.603
(0.0310)
|
| Week 26: 1 hour (n = 438, 206) |
2.938
(0.0256)
|
2.625
(0.0329)
|
| Week 26: 2 hours (n = 438, 203) |
2.977
(0.0225)
|
2.687
(0.0302)
|
| Week 26: 3 hours (n = 439, 204) |
3.016
(0.0270)
|
2.742
(0.0345)
|
| Week 26: 4 hours (n = 438, 205) |
2.962
(0.0225)
|
2.709
(0.0303)
|
| Week 26: 23 hours 15 min (n = 434, 206) |
2.884
(0.0257)
|
2.673
(0.0322)
|
| Week 26: 23 hours 45 min (n = 434, 206) |
2.859
(0.0234)
|
2.669
(0.0306)
|
| Title | FEV1 Area Under the Curve (AUC) (5 Min - 12 Hour) at Day 1, Week 12 and Week 26 |
|---|---|
| Description | 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. |
| Time Frame | Day 1, Week 12 and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Serial spirometry group, a sub-set of the full analysis set of patients. Twelve hour serial spirometry was conducted in this subset of patients in selected centers at Day 1. At week 12/13 and week 26/27 a 24 hour serial spirometry was performed. "n" is the number of patients with non-missing observations at each time point. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 169 | 83 |
| Day 1 (n = 169, 83) |
1.475
(0.0129)
|
1.320
(0.0173)
|
| Week 12 (n = 153, 75) |
1.433
(0.0179)
|
1.284
(0.0244)
|
| Week 26 (n = 149, 70) |
1.445
(0.0199)
|
1.238
(0.0274)
|
| Title | FEV1 Area Under Curve (AUC) (5 Min - 23 Hour 45 Min) at Week 12 and Week 26 |
|---|---|
| Description | 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. |
| Time Frame | Week 12 and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Serial spirometry group, a sub-set of the full analysis set of patients. Twelve hour serial spirometry was conducted in this subset of patients in selected centers at Day 1. At week 12/13 and week 26/27 a 24 hour serial spirometry was performed. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 169 | 83 |
| Week 12 (n = 153, 75) |
1.401
(0.0167)
|
1.268
(0.0228)
|
| Week 26 (n = 149, 70) |
1.412
(0.0185)
|
1.213
(0.0254)
|
| Title | Trough FEV1 and FVC at Day 1 and Week 26 |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. If one of the 23 h 15 min or 23 h 45 min values are missing then the remaining non-missing value is taken as trough FEV1 or trough FVC. If both values are missing, then their trough FEV1 or trough FVC is regarded as missing |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 534 | 260 |
| Day 1: FEV1 (n = 508, 248) |
1.414
(0.0075)
|
1.309
(0.0099)
|
| Week 26: FEV1 (n = 461, 217) |
1.387
(0.0112)
|
1.275
(0.0150)
|
| Day 1: FVC (n = 508, 248) |
2.901
(0.0154)
|
2.705
(0.0202)
|
| Week 26: FVC (n = 438, 208) |
2.867
(0.0236)
|
2.668
(0.0300)
|
| Title | Change in 24-hourly Mean Heart Rate at Day 1, Week 12 and Week 26 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 1, Week 12 and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety set included all patients who received at least one dose of study medication whether or not being randomized. A sub-set of the safety population had 24 hour Holter monitoring. "n" indicates patients with observations both at baseline and each endpoint. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 42 | 23 |
| Day 1: (n = 42, 23) |
-1.77
(7.583)
|
-1.28
(8.676)
|
| Week 12: (n = 42, 20) |
-1.99
(7.489)
|
-1.70
(7.230)
|
| Week 26: (n = 37, 22) |
-4.40
(9.347)
|
-2.60
(9.349)
|
| Title | Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations |
|---|---|
| Description | 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. |
| Time Frame | 26 Weeks and 30 Day follow-up |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety set included all patients who received at least one dose of study medication whether or not being randomized. Patients were randomized according to the treatment they received. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 550 | 267 |
| Participants with at least one AE |
317
57.6%
|
174
65.2%
|
| Death |
3
0.5%
|
3
1.1%
|
| SAE(s) |
41
7.5%
|
24
9%
|
| Discontinuation due to AE(s) |
32
5.8%
|
19
7.1%
|
| Discontinuation due to SAE(s) |
15
2.7%
|
8
3%
|
| Discontinuation due to non-SAE(s) |
18
3.3%
|
11
4.1%
|
| AE leading to dose interruption |
12
2.2%
|
8
3%
|
| AE requiring significant additional therapy |
246
44.7%
|
155
58.1%
|
| AE leading to new or prolonged hospitalization |
35
6.4%
|
21
7.9%
|
| Title | Rate of Moderate or Severe COPD Exacerbations Over the 26 Week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 534 | 260 |
| Number [exacerbations per year] |
0.43
|
0.59
|
| Title | Percentage of Nights With no Nighttime Awakenings Over the 26 Week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. At 26 weeks, the analysis is based on only patients with a value at both baseline and post-baseline. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 527 | 258 |
| Least Squares Mean (Standard Error) [percentage of nights with no awakenings] |
55.96
(1.537)
|
54.37
(1.970)
|
| Title | Percentage of Days With no Daytime Symptoms Over the 26 Week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. At 26 weeks, the analysis is based on only patients with a value at both baseline and post-baseline. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 528 | 258 |
| Least Squares Mean (Standard Error) [percentage of days with no symptoms] |
5.70
(0.799)
|
5.78
(1.076)
|
| Title | Percentage of Days Able to Perform Usual Daily Activities Over the 26 Week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. At 26 weeks, the analysis is based on only patients with a value at both baseline and post-baseline. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 528 | 258 |
| Least Squares Mean (Standard Error) [percentage of days] |
40.31
(1.473)
|
35.19
(1.907)
|
| Title | Mean Daily Total Symptom Score Over the 26 Week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. |
| Arm/Group Title | Glycopyrronium Bromide | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 534 | 260 |
| Least Squares Mean (Standard Error) [units on a scale] |
-1.54
(0.097)
|
-1.18
(0.129)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Glycopyrronium Bromide | Placebo | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Glycopyrronium Bromide | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Glycopyrronium Bromide | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 41/550 (7.5%) | 24/267 (9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/550 (0%) | 1/267 (0.4%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 3/550 (0.5%) | 0/267 (0%) | ||
| Bradycardia | 1/550 (0.2%) | 0/267 (0%) | ||
| Cardiac arrest | 0/550 (0%) | 1/267 (0.4%) | ||
| Cardiac failure congestive | 2/550 (0.4%) | 0/267 (0%) | ||
| Myocardial infarction | 2/550 (0.4%) | 1/267 (0.4%) | ||
| Myocardial ischaemia | 0/550 (0%) | 2/267 (0.7%) | ||
| Eye disorders | ||||
| Cataract | 1/550 (0.2%) | 0/267 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/550 (0%) | 1/267 (0.4%) | ||
| Colonic polyp | 1/550 (0.2%) | 0/267 (0%) | ||
| Diverticulum intestinal haemorrhagic | 0/550 (0%) | 1/267 (0.4%) | ||
| Dyspepsia | 1/550 (0.2%) | 0/267 (0%) | ||
| Gastric ulcer | 1/550 (0.2%) | 0/267 (0%) | ||
| Upper gastrointestinal haemorrhage | 1/550 (0.2%) | 0/267 (0%) | ||
| Vomiting | 0/550 (0%) | 1/267 (0.4%) | ||
| General disorders | ||||
| Death | 0/550 (0%) | 1/267 (0.4%) | ||
| Pyrexia | 0/550 (0%) | 1/267 (0.4%) | ||
| Hepatobiliary disorders | ||||
| Hepatic cirrhosis | 1/550 (0.2%) | 0/267 (0%) | ||
| Infections and infestations | ||||
| Lower respiratory tract infection bacterial | 0/550 (0%) | 1/267 (0.4%) | ||
| Pneumonia | 4/550 (0.7%) | 2/267 (0.7%) | ||
| Respiratory tract infection | 0/550 (0%) | 1/267 (0.4%) | ||
| Tracheobronchitis | 1/550 (0.2%) | 0/267 (0%) | ||
| Upper respiratory tract infection | 0/550 (0%) | 2/267 (0.7%) | ||
| Upper respiratory tract infection bacterial | 3/550 (0.5%) | 2/267 (0.7%) | ||
| Urinary tract infection bacterial | 0/550 (0%) | 1/267 (0.4%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 1/550 (0.2%) | 0/267 (0%) | ||
| Pelvic fracture | 1/550 (0.2%) | 0/267 (0%) | ||
| Rib fracture | 1/550 (0.2%) | 1/267 (0.4%) | ||
| Spinal compression fracture | 1/550 (0.2%) | 0/267 (0%) | ||
| Traumatic brain injury | 1/550 (0.2%) | 0/267 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/550 (0%) | 1/267 (0.4%) | ||
| Type 2 diabetes mellitus | 1/550 (0.2%) | 0/267 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Intervertebral disc protrusion | 1/550 (0.2%) | 0/267 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Bladder neoplasm | 0/550 (0%) | 1/267 (0.4%) | ||
| Hepatic neoplasm malignant | 1/550 (0.2%) | 0/267 (0%) | ||
| Lipoma | 1/550 (0.2%) | 0/267 (0%) | ||
| Lung neoplasm | 2/550 (0.4%) | 0/267 (0%) | ||
| Lung neoplasm malignant | 1/550 (0.2%) | 1/267 (0.4%) | ||
| Metastasis | 1/550 (0.2%) | 0/267 (0%) | ||
| Non-Hodgkin's lymphoma | 1/550 (0.2%) | 0/267 (0%) | ||
| Squamous cell carcinoma of skin | 0/550 (0%) | 1/267 (0.4%) | ||
| Thyroid cancer | 0/550 (0%) | 1/267 (0.4%) | ||
| Nervous system disorders | ||||
| Cerebrovascular accident | 1/550 (0.2%) | 0/267 (0%) | ||
| Syncope | 2/550 (0.4%) | 0/267 (0%) | ||
| Psychiatric disorders | ||||
| Confusional state | 1/550 (0.2%) | 0/267 (0%) | ||
| Depression | 1/550 (0.2%) | 0/267 (0%) | ||
| Suicidal ideation | 1/550 (0.2%) | 0/267 (0%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 0/550 (0%) | 1/267 (0.4%) | ||
| Renal failure acute | 1/550 (0.2%) | 0/267 (0%) | ||
| Urinary retention | 1/550 (0.2%) | 0/267 (0%) | ||
| Reproductive system and breast disorders | ||||
| Prostatomegaly | 1/550 (0.2%) | 0/267 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 1/550 (0.2%) | 0/267 (0%) | ||
| Atelectasis | 1/550 (0.2%) | 0/267 (0%) | ||
| Chronic obstructive pulmonary disease | 9/550 (1.6%) | 11/267 (4.1%) | ||
| Dyspnoea | 2/550 (0.4%) | 0/267 (0%) | ||
| Hypoxia | 1/550 (0.2%) | 0/267 (0%) | ||
| Pleural effusion | 1/550 (0.2%) | 0/267 (0%) | ||
| Respiratory failure | 2/550 (0.4%) | 0/267 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis psoriasiform | 1/550 (0.2%) | 0/267 (0%) | ||
| Vascular disorders | ||||
| Aortic stenosis | 1/550 (0.2%) | 0/267 (0%) | ||
| Deep vein thrombosis | 1/550 (0.2%) | 0/267 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Glycopyrronium Bromide | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 132/550 (24%) | 85/267 (31.8%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 28/550 (5.1%) | 21/267 (7.9%) | ||
| Upper respiratory tract infection | 23/550 (4.2%) | 20/267 (7.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 105/550 (19.1%) | 67/267 (25.1%) | ||
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 (i.e., data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT01005901
Other Study ID Numbers:
- CNVA237A2304
- 2009-013504-32
First Posted:
Nov 1, 2009
Last Update Posted:
Apr 12, 2012
Last Verified:
Dec 1, 2011