Long-term Extension Study of the Safety, Tolerability, and Efficacy of Aclidinium Bromide in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-36)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00970268
• Collaborator: (none)
• Enrollment: 291
• Locations: 83
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this extension study is to evaluate the long-term safety, tolerability, and efficacy of inhaled aclidinium bromide at two dose levels in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This study will be 54 weeks in duration; a 52-week double-blind treatment period and 2 week follow-up phone call, following a 12 week lead-in study. All patients will be randomized from the lead-in study at one of two doses of aclidinium.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Aclidinium bromide; Drug: Aclidinium bromide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 291 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Long-term, Randomized, Double-blind Extension Study of the Safety, Tolerability, and Efficacy of Aclidinium Bromide at Two Dose Levels When Administered to Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Aclidinium bromide dose, inhaled, for 52 weeks of treatment	Drug: Aclidinium bromide; Aclidinium bromide 200 μg, oral inhalation twice per day for 52 weeks of treatment
Experimental: 2 Aclidinium bromide dose, inhaled, for 52 weeks of treatment	Drug: Aclidinium bromide; Aclidinium bromide 400 μg, oral inhalation twice per day for 52 weeks of treatment

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) [Change from baseline (visit 2 of lead-in study LAS-MD-33) to 52 weeks]

   Change From Baseline (Visit 2 of lead-in Study NCT00891462, [LAS-MD-33]) to Week 52 (Week 64 From Start of NCT00891462, [LAS-MD-33]) in Morning Predose (Trough) FEV1

Secondary Outcome Measures

1. Change From Baseline in Peak FEV1 [52 weeks]

   Change From Baseline (Visit 2 of study NCT00891462, [LAS-MD-33])in Peak FEV1 in liters at Week 52 (Week 64 from the start of NCT00891462, [LAS-MD-33]).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Completion of a lead-in study (NCT00891462)

Exclusion Criteria:

• Use or anticipated use of any medication prohibited in this study

• Evidence of abnormal clinical laboratory values, vital signs, or electrocardiographic (ECG) results or the presence of abnormities in physical examination findings

• The presence of anti-cholinergic effects (eg, dry mouth, urinary retention, narrow angle glaucoma)

• QTcB of >500 msec on both the pre-dose and post-dose ECG

• Women who are pregnant, intend to become pregnant, or are breast-feeding

• A life expectancy of less than 1 year

• Noncompliance with IP dosing and/or attending clinic visits during the lead-in study

• Significant interruption of double-blind therapy during the transition from the lead-in study into the extension study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 1162	Birmingham	Alabama	United States	35209
2	Forest Investigative Site 1127	Mobile	Alabama	United States	36608
3	Forest Investigative Site 0909	Glendale	Arizona	United States	85306
4	Forest Investigative Site 2060	Phoenix	Arizona	United States	85023
5	Forest Investigative Site 2065	Fullerton	California	United States	92835
6	Forest Investigative Site 1088	Lakewood	California	United States	90712
7	Forest Investigative Site 1122	Orange	California	United States	92868
8	Forest Investigative Site 2029	Rancho Mirage	California	United States	92270
9	Forets Investigative Site 2064	Riverside	California	United States	92506
10	Forest Investigative Site 0517	Sacramento	California	United States	95821
11	Forest Investigative Site 2009	San Diego	California	United States	92120
12	Forest Investigative Site 1137	Colorado Springs	Colorado	United States	80907
13	Forest Investigative Site 2100	Waterbury	Connecticut	United States	06708
14	Forest Investigative Site 1154	Brandon	Florida	United States	33511
15	Forest Investigative Site 1152	Clearwater	Florida	United States	33765
16	Forest Investigative Site 0670	DeLand	Florida	United States	32720
17	Forest Investigative Site 0990	Fort Lauderdale	Florida	United States	33316
18	Forest Investigative Site 1167	Melbourne	Florida	United States	32935
19	Forest Investigative Site 1060	Ormond Beach	Florida	United States	32174
20	Forest Investigative Site 0974	Pensacola	Florida	United States	32504
21	Forest Investigative Site 2082	Tamarac	Florida	United States	33321
22	Forest Investigative Site 2053	Tampa	Florida	United States	33606
23	Forest Investigative Site 2047	Tampa	Florida	United States	33613
24	Forest Investigative Site 1185	Winter Park	Florida	United States	32789
25	Forest Investigative Site 1183	Atlanta	Georgia	United States	30329
26	Forest Investigative Site 0987	Austell	Georgia	United States	30106
27	Forest Investigative Site 1101	Blue Ridge	Georgia	United States	30513
28	Forest Investigative Site 1180	Decatur	Georgia	United States	30033
29	Forest Investigative Site 1161	Duluth	Georgia	United States	30096
30	Forest Investigative Site 2051	River Forest	Illinois	United States	60305
31	Forest Investigative Site 0989	Skokie	Illinois	United States	60076
32	Forest Investigative Site 1149	South Bend	Indiana	United States	46617
33	Forest Investigative Site 2085	Crescent Springs	Kentucky	United States	41017
34	Forest Investigative Site 0539	Lexington	Kentucky	United States	40504
35	Forest Investigative Site 2024	Lafayette	Louisiana	United States	70503
36	Forest Investigative Site 2040	Biddeford	Maine	United States	04005
37	Forest Investigative Site 1128	Edina	Minnesota	United States	55435
38	Forest Investigative Site 2041	Minneapolis	Minnesota	United States	55402
39	Forest Investigative Site 1124	Minneapolis	Minnesota	United States	55407
40	Forest Investigative Site 1100	Florissant	Missouri	United States	63033
41	Forest Investigative Site 2079	St. Charles	Missouri	United States	63301
42	Forest Investigative Site 2067	Butte	Montana	United States	59701
43	Forest Investigative Site 1169	Papillion	Nebraska	United States	68406
44	Forest Investigative Site 1150	Berlin	New Jersey	United States	08009
45	Forest Investigative Site 2084	Summit	New Jersey	United States	07901
46	Forest Investigative Site 1147	Brooklyn	New York	United States	11234
47	Forest Investigative Site 1119	Elmira	New York	United States	14901
48	Forest Investigative Site 1151	New Hyde Park	New York	United States	11040
49	Forest Investigative Site 1141	New York	New York	United States	10016
50	Forest Investigative Site 1163	New York	New York	United States	10016
51	Forest Investigative Site 1130	Asheville	North Carolina	United States	28801
52	Forest Investigative Site 1134	Canton	Ohio	United States	44718
53	Forest Investigative Site 1181	Centerville	Ohio	United States	45459
54	Forest Investigative Site 1136	Cincinnati	Ohio	United States	45227
55	Forest Investigative Site 2007	Cincinnati	Ohio	United States	45231
56	Forest Investigative Site 2028	Cincinnati	Ohio	United States	45242
57	Forest Investigative Site 0959	Columbus	Ohio	United States	43215
58	Forest Investigative Site 2006	Columbus	Ohio	United States	43215
59	Forest Investigative Site 2043	Medford	Oregon	United States	97504
60	Forest Investigative Site 1106	Portland	Oregon	United States	97213
61	Forest Investigative Site 1126	Bethlehem	Pennsylvania	United States	18020
62	Forest Investigative Site 2016	Erie	Pennsylvania	United States	16506
63	Forest Investigative Site 1146	Pittsburgh	Pennsylvania	United States	15243
64	Forest Investigative Site 1158	Upland	Pennsylvania	United States	19013
65	Forest Investigative Site 1089	East Providence	Rhode Island	United States	02914
66	Forest Investigative Site 1144	Johnston	Rhode Island	United States	02919
67	Forest Investigative Site 2072	Charleston	South Carolina	United States	29406
68	Forest Investigative Site 1078	Greenville	South Carolina	United States	29615
69	Forest Investigative Site 2080	Greer	South Carolina	United States	29651
70	Forest Investigative Site 1121	Spartanburg	South Carolina	United States	29303
71	Forest Investigative Site 1155	Dallas	Texas	United States	75231
72	Forest Investigative Site 2012	Fort Worth	Texas	United States	76104
73	Forest Investigative Site 1165	San Antonio	Texas	United States	78229
74	Forest Investigative Site 1129	Waco	Texas	United States	76712
75	Forest Investigative Site 2099	Richmond	Virginia	United States	23225
76	Forest Investigative Site 1142	Spokane	Washington	United States	99204
77	Forest Investigative Site 0988	Tacoma	Washington	United States	98405
78	Forest Investigative Site 2201	Kelowna	British Columbia	Canada	V1Y 8E7
79	Forest Investigative Site 1177	Vancouver	British Columbia	Canada	V5Z 4E1
80	Forest Investigative Site 2200	Niagara Falls	Ontario	Canada	L2g 1J4
81	Forest Investigative Site 1168	Toronto	Ontario	Canada	M5G 1N8
82	Forest Investigative Site 1171	Toronto	Ontario	Canada	M5T 3A9
83	Forest Investigative Site 2203	Toronto	Ontario	Canada	M6H 3M2

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Esther Garcia, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00970268
• Other Study ID Numbers: LAS-MD-36
• First Posted: Sep 2, 2009
• Last Update Posted: Jan 6, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by AstraZeneca: COPD; Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; Emphysema; Airflow Obstruction, Chronic; Chronic Airflow Obstruction; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Bromides

Study Results

Participant Flow

Recruitment Details	Patient recruitment occurred from August of 2009 to March of 2010 and was by invitation only to patients who had completed study NCT00891462 (LAS-MD-33). In total, there were 77 individual study sites, 71 in the United States and 6 additional sites in Canada.
Pre-assignment Detail	From the total of 291 patients enrolled, 289 patients (99.3%) received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 246 (84.5%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent To Treat (ITT) Population.

Arm/Group Title	Aclidinium Bromide 200 μg	Aclidinium Bromide 400 μg
Arm/Group Description	Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment.
Period Title: Overall Study
STARTED	139	152
COMPLETED	96	103
NOT COMPLETED	43	49

Baseline Characteristics

Arm/Group Title	Aclidinium Bromide 200 μg	Aclidinium Bromide 400 μg	Total
Arm/Group Description	Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment.	Total of all reporting groups
Overall Participants	137	152	289
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.3 (10.1)	64.4 (10.0)	63.9 (9.9)
Age, Customized (participants) [Number]
≥ 40 to < 60 years	49 35.8%	40 26.3%	89 30.8%
≥ 60 to < 70 years	51 37.2%	67 44.1%	118 40.8%
≥ 70 years	37 27%	45 29.6%	82 28.4%
Gender (Count of Participants)
Female	63 46%	76 50%	139 48.1%
Male	74 54%	76 50%	150 51.9%
Region of Enrollment (participants) [Number]
United States	128 93.4%	138 90.8%	266 92%
Canada	9 6.6%	14 9.2%	23 8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)
Description	Change From Baseline (Visit 2 of lead-in Study NCT00891462, [LAS-MD-33]) to Week 52 (Week 64 From Start of NCT00891462, [LAS-MD-33]) in Morning Predose (Trough) FEV1
Time Frame	Change from baseline (visit 2 of lead-in study LAS-MD-33) to 52 weeks

Outcome Measure Data

Analysis Population Description

From the total of 291 patients enrolled, 289 patients (99.3%) received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 246 (84.5%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the ITT Population

Arm/Group Title	Placebo - Aclidinium Bromide 200 μg	Aclidinium Bromide 200 μg - Aclidinium Bromide 200 μg	Placebo - Aclidinium Bromide 400 μg	Aclidinium Bromide 400 μg - Aclidinium Bromide 400 μg
Arm/Group Description	Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 200 micrograms of Aclidinium bromide for 12 weeks in the lead-in study.	Aclidinium bromide, 400 microgram dose, oral inhalation, twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 400 microgram of Aclidinium bromide for 12 weeks in the lead-in study.
Measure Participants	38	76	41	91
Least Squares Mean (Standard Error) [L]	-0.035 (0.040)	0.069 (0.028)	0.069 (0.037)	0.056 (0.025)

2. Secondary Outcome

Title	Change From Baseline in Peak FEV1
Description	Change From Baseline (Visit 2 of study NCT00891462, [LAS-MD-33])in Peak FEV1 in liters at Week 52 (Week 64 from the start of NCT00891462, [LAS-MD-33]).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo - Aclidinium Bromide 200 μg	Aclidinium Bromide 200 μg - Aclidinium Bromide 200 μg	Placebo - Aclidinium Bromide 400 μg	Aclidinium Bromide 400 μg - Aclidinium Bromide 400 μg
Arm/Group Description	Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 200 micrograms of Aclidinium bromide for 12 weeks in the lead-in study.	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment for patients who received 12 weeks of placebo in the lead-in study.	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment in patients who also received 400 micrograms of Aclidinium bromide for 12 weeks in the lead-in study.
Measure Participants	38	76	41	91
Least Squares Mean (Standard Error) [L]	0.111 (0.040)	0.213 (0.028)	0.222 (0.038)	0.219 (0.025)

Adverse Events

Time Frame	Adverse Event Reporting occurred from August 2009 to November 2010 at 77 study sites (71 in the United States and 6 additional sites in Canada).
Arm/Group Title	Placebo to Aclidinium Bromide 200 μg		Aclidinium Bromide 200 μg to Aclidinium Bromide 200 μg		Placebo to Aclidinium Bromide 400μg		Aclidinium Bromide 400μg to Aclidinium Bromide 400μg
Arm/Group Description	Patients were given 12 weeks of placebo, then switched to Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment		Patients were given 12 weeks of Aclidinium bromide, 200 microgram dose, then continued with the 200 microgram dose, oral inhalation twice per day for an additional 52 weeks of treatment.		Patients were given 12 weeks of placebo, then switched to Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment		Patients were given 12 weeks of Aclidinium bromide, 400 microgram dose, then continued with the 400 microgram dose twice per day, oral inhalation, for an additional 52 weeks of treatment.
All Cause Mortality
	Placebo to Aclidinium Bromide 200 μg		Aclidinium Bromide 200 μg to Aclidinium Bromide 200 μg		Placebo to Aclidinium Bromide 400μg		Aclidinium Bromide 400μg to Aclidinium Bromide 400μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo to Aclidinium Bromide 200 μg		Aclidinium Bromide 200 μg to Aclidinium Bromide 200 μg		Placebo to Aclidinium Bromide 400μg		Aclidinium Bromide 400μg to Aclidinium Bromide 400μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/44 (15.9%)		13/93 (14%)		7/46 (15.2%)		13/106 (12.3%)
Cardiac disorders
Acute myocardial infarction	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Angina pectoris	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Atrial flutter	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Cardiogenic shock	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Coronary artery disease	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Ventricular fibrillation	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Acute coronary syndrome	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Angina unstable	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Gastrointestinal disorders
Colitis	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Oesophagitis	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Constipation	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Haemorrhoidal haemorrhage	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Small intestinal obstruction	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
General disorders
Non-cardiac chest pain	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Infections and infestations
Pneumonia	1/44 (2.3%)		3/93 (3.2%)		0/46 (0%)		2/106 (1.9%)
Influenza	0/44 (0%)		0/93 (0%)		1/46 (2.2%)		0/106 (0%)
Lower respiratory tract infection	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Pneumonia bacterial	0/44 (0%)		0/93 (0%)		1/46 (2.2%)		0/106 (0%)
Staphylococcal infection	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Gastroenteritis	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Lobar pneumonia	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Postoperative wound infection	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/44 (0%)		0/93 (0%)		1/46 (2.2%)		0/106 (0%)
Spinal compression fracture	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Contusion	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Dyspepsia	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Femoral neck fracture	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Multiple drug overdose accidental	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Thermal burn	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Upper limb fracture	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Metabolism and nutrition disorders
Dehydration	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Hypovolaemia	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Back pain	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Neck pain	0/44 (0%)		0/93 (0%)		1/46 (2.2%)		0/106 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/44 (0%)		0/93 (0%)		1/46 (2.2%)		0/106 (0%)
Breast cancer stage II	0/44 (0%)		0/93 (0%)		1/46 (2.2%)		0/106 (0%)
Lung squamous cell carcinoma stage unspecified	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Small cell lung cancer stage unspecified	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Nervous system disorders
Haemorrhagic stroke	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Carotid artery stenosis	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Syncope	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Renal and urinary disorders
Renal failure acute	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	2/44 (4.5%)		3/93 (3.2%)		1/46 (2.2%)		6/106 (5.7%)
Respiratory failure	0/44 (0%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Acute respiratory failure	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Pulmonary oedema	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		0/106 (0%)
Vascular disorders
Hypertension	1/44 (2.3%)		0/93 (0%)		0/46 (0%)		1/106 (0.9%)
Haematoma	0/44 (0%)		1/93 (1.1%)		0/46 (0%)		0/106 (0%)
Other (Not Including Serious) Adverse Events
	Placebo to Aclidinium Bromide 200 μg		Aclidinium Bromide 200 μg to Aclidinium Bromide 200 μg		Placebo to Aclidinium Bromide 400μg		Aclidinium Bromide 400μg to Aclidinium Bromide 400μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/44 (81.8%)		63/93 (67.7%)		28/46 (60.9%)		64/106 (60.4%)
Cardiac disorders
Bundle branch block left	3/44 (6.8%)		3/93 (3.2%)		0/46 (0%)		3/106 (2.8%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	3/44 (6.8%)		0/93 (0%)		1/46 (2.2%)		2/106 (1.9%)
Nausea	4/44 (9.1%)		1/93 (1.1%)		1/46 (2.2%)		2/106 (1.9%)
General disorders
Fatigue	4/44 (9.1%)		3/93 (3.2%)		0/46 (0%)		3/106 (2.8%)
Pyrexia	3/44 (6.8%)		0/93 (0%)		0/46 (0%)		3/106 (2.8%)
Infections and infestations
Nasopharyngitis	4/44 (9.1%)		8/93 (8.6%)		4/46 (8.7%)		10/106 (9.4%)
Urinary tract infection	4/44 (9.1%)		4/93 (4.3%)		3/46 (6.5%)		8/106 (7.5%)
Upper respiratory tract infection	5/44 (11.4%)		6/93 (6.5%)		2/46 (4.3%)		6/106 (5.7%)
Bronchitis	3/44 (6.8%)		1/93 (1.1%)		1/46 (2.2%)		4/106 (3.8%)
Sinusitis	5/44 (11.4%)		6/93 (6.5%)		1/46 (2.2%)		3/106 (2.8%)
Pneumonia	3/44 (6.8%)		4/93 (4.3%)		1/46 (2.2%)		2/106 (1.9%)
Injury, poisoning and procedural complications
Fall	0/44 (0%)		6/93 (6.5%)		3/46 (6.5%)		2/106 (1.9%)
Contusion	0/44 (0%)		6/93 (6.5%)		5/46 (10.9%)		1/106 (0.9%)
Investigations
Blood glucose increased	3/44 (6.8%)		3/93 (3.2%)		3/46 (6.5%)		0/106 (0%)
Musculoskeletal and connective tissue disorders
Back pain	2/44 (4.5%)		7/93 (7.5%)		0/46 (0%)		5/106 (4.7%)
Arthralgia	2/44 (4.5%)		5/93 (5.4%)		3/46 (6.5%)		4/106 (3.8%)
Nervous system disorders
Headache	3/44 (6.8%)		5/93 (5.4%)		2/46 (4.3%)		4/106 (3.8%)
Psychiatric disorders
Insomnia	2/44 (4.5%)		2/93 (2.2%)		2/46 (4.3%)		6/106 (5.7%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disorder	16/44 (36.4%)		23/93 (24.7%)		14/46 (30.4%)		24/106 (22.6%)
Oropharyngeal pain	2/44 (4.5%)		2/93 (2.2%)		0/46 (0%)		6/106 (5.7%)
Cough	2/44 (4.5%)		7/93 (7.5%)		4/46 (8.7%)		4/106 (3.8%)
Dyspnoea	1/44 (2.3%)		7/93 (7.5%)		4/46 (8.7%)		4/106 (3.8%)
Skin and subcutaneous tissue disorders
Rash	1/44 (2.3%)		2/93 (2.2%)		1/46 (2.2%)		6/106 (5.7%)
Vascular disorders
Hypertension	3/44 (6.8%)		4/93 (4.3%)		1/46 (2.2%)		3/106 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.