Evaluate the Efficacy and Safety of GSK573719 Delivered Via a Novel Dry Powder Inhaler in Subjects With COPD

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01387230
• Collaborator: (none)
• Enrollment: 206
• Locations: 27
• Arms: 2
• Duration (Months): 7.5
• Patients Per Site: 7.6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess if 12 weeks' treatment with GSK573719 Inhalation Powder is safe and effective compared with placebo or no active drug intake, when administered once-daily in subjects with Chronic Obstructive Pulmonary Disease (COPD).

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK573719; Drug: GSK573719; Other: Placebo	Phase 3

Detailed Description

Inhaled bronchodilators, such as beta 2 agonists and anticholinergics, and inhaled corticosteroids are the mainstays of therapy in patients diagnosed with COPD. Anticholinergic bronchodilators or long acting muscarinic receptor antagonists function by blocking endogenous airway smooth muscle cholinergic tone. Treatment with anticholinergics has been shown to significantly improve forced expiratory volume in 1 second (FEV1), resting and dynamic lung hyperinflation, symptoms, and exercise capacity in patients with COPD. Currently tiotropium is the only approved long acting muscarinic antagonist available for treatment of COPD.This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder of 2 doses when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD. There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. There will be 8 clinic visits during three of which serial spirometry will be performed . The total duration of subject participation in the study will be approximately 14 weeks.

This is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder 62.5 mcg and 125 mcg when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD.

Eligible subjects will be randomized 1:1:1 to receive either of the two doses of GSK573719 Inhalation Powder doses or placebo for 12 weeks.

There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. Clinic visits will be at Screening, Randomization (Visit 2), Day 3 and Weeks 2, 4, 8, and 12, and 1 day after the Week 12 visit (Visits 1 to 8, respectively). A safety follow-up assessment will be conducted by telephone approximately 7 days after the end of the study treatment (FU Phone Contact). The total duration of subject participation, including the follow-up period will be approximately 14 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the run-in and treatment periods.

Pre-dose spirometry will be conducted at each clinic visit. Six hour post-dose serial spirometry will be conducted at Visit 2 and at Visits 5 and 7. All subjects will be provided with a paper diary for completion everyday throughout the run-in period and 12-week treatment period. Subjects will use the diary to record their daily use of supplemental albuterol/salbutamol and to record any medical problems experienced and any medications used.

At Visit 2 the Baseline Dyspnea Index (BDI) will be administered. The Transition Dyspnea Index (TDI) will be administered at Visits 5, 6, and 7.

Disease specific health status will be evaluated using the St. George's Respiratory Questionnaire (SGRQ) at Visit 2 and Visits 5, 6 and 7. Vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and blood biochemistry) including pharmacokinetic samples will be obtained at selected clinic visits.

Approximately 198 subjects will be randomized to ensure at least 168 subjects complete the treatment period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of GSK573719 Delivered Once-Daily Via a Novel Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 13, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK573719 active drug	Drug: GSK573719; 62.5 mcg; Drug: GSK573719; 125mcg
Placebo Comparator: Placebo no active drug	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 [Baseline and Day 85]

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56, 84, and 85. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions.

Secondary Outcome Measures

1. Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) [Baseline and Days 1, 28 and 84]

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1, 28, and Day 84 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 1 hour, 3 hours, and 6 hours. Change from Baseline was the WM minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions.

2. Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) [Baseline, Day 1 and Day 84]

   Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 measurements of interest for Day 1 were collected at 1, 3, 6, 23 and 24 hours post-dose on Day 1 and for Day 84, the measures were pre-dose (24 hours post-dose of Day 83 morning dose but prior to Day 84's dose) and 1, 3, 6, 23 and 24 hours post dose on Day 84. Baseline is the mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis performed separately by Visit/Day using a repeated measures model with covariates of treatment, Baseline, smoking status, center group, time, time by Baseline and time by treatment interactions.

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

• 10 pack-year or greater history of cigarette smoking

• Post-bronchodilator FEV1/FVC of <0.7

• Predicted FEV1 of 70% of normal or less

• Modified Medical Research Council (mMRC) dyspnea score of 2 or greater

Exclusion Criteria:

• Women who are pregnant, lactating, or planning to become pregnant

• Respiratory disorders other than COPD, including a current diagnosis of asthma

• Clinically significant non-respiratory diseases or abnormalities that are not adequately controlled

• Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, or the excipients of magnesium stereate or lactose used in the inhaler delivery device

• Hospitalization for COPD or pneumonia within 12 weeks prior to screening

• Lung volume reduction surgery within 12 weeks prior to screening

• Abnormal and clinically significant ECG findings at screening

• Clinically significant laboratory findings at screening

• Use of systemic corticosteroids, antibiotics for respiratory tract infections, high dose inhaled steroids (>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, inhaled sodium cromoglycate or nedocromil sodium, or investigational medicines for defined time periods prior to the screening visit

• Use of long-term oxygen therapy (12 hours or greater per day)

• Regular use of nebulized treatment with short-acting bronchodilators

• Participation in the acute phase of a pulmonary rehabilitation program

• A know or suspected history of alcohol or drug abuse

• Affiliation with the investigational site

• Previous use of GSK573719 or the combination of GSK573719/GW642444

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Sunset	Louisiana	United States	70584
2	GSK Investigational Site	Easley	South Carolina	United States	29640
3	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
4	GSK Investigational Site	Union	South Carolina	United States	29379
5	GSK Investigational Site	Frankfurt	Hessen	Germany	60389
6	GSK Investigational Site	Gelnhausen	Hessen	Germany	63571
7	GSK Investigational Site	Kassel	Hessen	Germany	34121
8	GSK Investigational Site	Hannover	Niedersachsen	Germany	30173
9	GSK Investigational Site	Weyhe-Leeste	Niedersachsen	Germany	28844
10	GSK Investigational Site	Goch	Nordrhein-Westfalen	Germany	47574
11	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	51069
12	GSK Investigational Site	Solingen	Nordrhein-Westfalen	Germany	42651
13	GSK Investigational Site	Koblenz	Rheinland-Pfalz	Germany	56068
14	GSK Investigational Site	Teuchern	Sachsen-Anhalt	Germany	06682
15	GSK Investigational Site	Leipzg	Sachsen	Germany	04109
16	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
17	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
18	GSK Investigational Site	Berlin		Germany	10117
19	GSK Investigational Site	Berlin		Germany	10367
20	GSK Investigational Site	Berlin		Germany	10717
21	GSK Investigational Site	Berlin		Germany	13086
22	GSK Investigational Site	Berlin		Germany	13187
23	GSK Investigational Site	Ibaraki		Japan	319-1113
24	GSK Investigational Site	Kagawa		Japan	762-0031
25	GSK Investigational Site	Kyoto		Japan	612-0026
26	GSK Investigational Site	Osaka		Japan	530-0001
27	GSK Investigational Site	Tokyo		Japan	103-0027

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01387230
• Other Study ID Numbers: 115408
• First Posted: Jul 4, 2011
• Last Update Posted: Nov 9, 2017
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: chronic obstructive pulmonary disease; long acting muscarinic antagonist
• Additional relevant MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Pre-assignment Detail	Participants (par.) who met eligibility criteria at Screening (Visit 1) completed a 5- to 9-day run-in period and were then randomized to a 12-week treatment period. A total of 246 par. were screened; 206 par. who were eligible were randomized and 206 par. received at least one dose of study drug.

Arm/Group Title	Placebo	UMEC 62.5 µg QD	UMEC 125 µg QD
Arm/Group Description	Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 12 weeks.	Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) QD via a DPI in the morning for 12 weeks.	Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Period Title: Overall Study
STARTED	68	69	69
COMPLETED	50	62	56
NOT COMPLETED	18	7	13

Baseline Characteristics

Arm/Group Title	Placebo	UMEC 62.5 µg	UMEC 125 µg	Total
Arm/Group Description	Participants received matching placebo QD via a DPI in the morning for 12 weeks.	Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	Total of all reporting groups
Overall Participants	68	69	69	206
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.5 (8.72)	62.3 (9.50)	64.6 (7.96)	63.1 (8.77)
Sex: Female, Male (Count of Participants)
Female	26 38.2%	25 36.2%	27 39.1%	78 37.9%
Male	42 61.8%	44 63.8%	42 60.9%	128 62.1%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	1 1.5%	1 1.4%	2 2.9%	4 1.9%
Asian - Japanese Heritage	8 11.8%	7 10.1%	6 8.7%	21 10.2%
White - Arabic/North African Heritage	1 1.5%	1 1.4%	0 0%	2 1%
White - White/Caucasian/European Heritage	58 85.3%	60 87%	61 88.4%	179 86.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
Description	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56, 84, and 85. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions.
Time Frame	Baseline and Day 85

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized par. who received >=1 dose of study drug. Par. analyzed are those with data available at the presented time point; but, all par. without missing covariate information and with >=1 post-BL measurement were included in the analysis.

Arm/Group Title	Placebo	UMEC 62.5 µg	UMEC 125 µg
Arm/Group Description	Participants received matching placebo QD via a DPI in the morning for 12 weeks.	Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Measure Participants	50	61	55
Least Squares Mean (Standard Error) [Liters]	-0.007 (0.0280)	0.120 (0.0257)	0.145 (0.0268)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, UMEC 62.5 µg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM)
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.127
	Confidence Interval	(2-Sided) 95%; 0.052 to 0.202
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least squares mean difference=UMEC 62.5 µg minus Placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, UMEC 125 µg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM)
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.152
	Confidence Interval	(2-Sided) 95%; 0.076 to 0.229
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least squares mean difference=UMEC 125 µg minus Placebo.

2. Secondary Outcome

Title	Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12)
Description	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1, 28, and Day 84 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 1 hour, 3 hours, and 6 hours. Change from Baseline was the WM minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions.
Time Frame	Baseline and Days 1, 28 and 84

Outcome Measure Data

Analysis Population Description

ITT Population. All participants with >=1 post-BL assessment and non-missing covariate data are included in the analysis. Different participants may have been analyzed at different time points (represented by n=X, X, X in the category titles), so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Placebo	UMEC 62.5 µg	UMEC 125 µg
Arm/Group Description	Participants received matching placebo QD via a DPI in the morning for 12 weeks.	Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Measure Participants	68	69	69
Day 1, n=66, 69, 69	0.017 (0.0150)	0.141 (0.0147)	0.164 (0.0147)
Day 28, n= 53, 65, 60	-0.024 (0.0223)	0.141 (0.0206)	0.172 (0.0212)
Day 84, n= 49, 60, 56	-0.003 (0.0271)	0.163 (0.0248)	0.188 (0.0256)

3. Secondary Outcome

Title	Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12)
Description	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 measurements of interest for Day 1 were collected at 1, 3, 6, 23 and 24 hours post-dose on Day 1 and for Day 84, the measures were pre-dose (24 hours post-dose of Day 83 morning dose but prior to Day 84's dose) and 1, 3, 6, 23 and 24 hours post dose on Day 84. Baseline is the mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis performed separately by Visit/Day using a repeated measures model with covariates of treatment, Baseline, smoking status, center group, time, time by Baseline and time by treatment interactions.
Time Frame	Baseline, Day 1 and Day 84

Outcome Measure Data

Analysis Population Description

ITT Population. All participants with >=1 post-BL assessment and non-missing covariate data are included in the analysis. Different participants may have been analyzed at different time points (represented by n=X, X, X in the category titles), so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Placebo	UMEC 62.5 µg	UMEC 125 µg
Arm/Group Description	Participants received matching placebo QD via a DPI in the morning for 12 weeks.	Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Measure Participants	68	69	69
Day 1, 1 hour, n=68, 69, 69	-0.001 (0.0148)	0.132 (0.0147)	0.142 (0.0147)
Day 1, 3 hours ,n=68, 69, 69	0.035 (0.0187)	0.165 (0.0186)	0.210 (0.0186)
Day 1, 6 hours, n=66, 69, 69	0.000 (0.0206)	0.156 (0.0203)	0.169 (0.0203)
Day 1, 23 hours, n=67, 69, 65	-0.027 (0.0178)	0.070 (0.0176)	0.113 (0.0180)
Day 1, 24 hours, n=67, 69, 66	-0.020 (0.0190)	0.099 (0.0188)	0.151 (0.0191)
Day 84, Pre-dose, n=50, 60, 56	0.002 (0.0299)	0.155 (0.0269)	0.177 (0.0283)
Day 84, 1 hour,n=50, 60, 56	-0.025 (0.0299)	0.167 (0.0270)	0.199 (0.0283)
Day 84, 3 hours, n=50, 61, 56	0.012 (0.0301)	0.189 (0.0271)	0.219 (0.0285)
Day 84, 6 hours,n=49, 61, 56	0.006 (0.0286)	0.159 (0.0257)	0.178 (0.0270)
Day 84, 23 hours, n=50, 60, 55	-0.019 (0.0301)	0.106 (0.0271)	0.142 (0.0286)
Day 84, 24 hours, n=50, 61, 55	0.020 (0.0299)	0.142 (0.0269)	0.170 (0.0284)

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 12 weeks).
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.
Arm/Group Title	Placebo		UMEC 62.5 µg		UMEC 125 µg
Arm/Group Description	Participants received matching placebo QD via a DPI in the morning for 12 weeks.		Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.		Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
All Cause Mortality
	Placebo		UMEC 62.5 µg		UMEC 125 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		UMEC 62.5 µg		UMEC 125 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/68 (1.5%)		1/69 (1.4%)		2/69 (2.9%)
Cardiac disorders
Coronary artery stenosis	0/68 (0%)		0/69 (0%)		1/69 (1.4%)
General disorders
Non-cardiac chest pain	1/68 (1.5%)		0/69 (0%)		0/69 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	0/68 (0%)		1/69 (1.4%)		0/69 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/68 (0%)		0/69 (0%)		1/69 (1.4%)
Other (Not Including Serious) Adverse Events
	Placebo		UMEC 62.5 µg		UMEC 125 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/68 (23.5%)		12/69 (17.4%)		19/69 (27.5%)
Infections and infestations
Nasopharyngitis	7/68 (10.3%)		8/69 (11.6%)		7/69 (10.1%)
Musculoskeletal and connective tissue disorders
Back pain	4/68 (5.9%)		2/69 (2.9%)		0/69 (0%)
Nervous system disorders
Headache	7/68 (10.3%)		5/69 (7.2%)		10/69 (14.5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/68 (1.5%)		0/69 (0%)		5/69 (7.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.