Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-33)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00891462
• Collaborator: (none)
• Enrollment: 561
• Locations: 112
• Arms: 3
• Duration (Months): 7
• Patients Per Site: 5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy (effectiveness) and safety of aclidinium bromide doses as compared to placebo in the treatment of moderate to severe chronic obstructive pulmonary disease. The study will be 16 weeks in duration; 2-week run-in period, 12-week double-blind treatment, and 2-week follow-up phone visit.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 561 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Aclidinium Bromide at Two Dose Levels (200 μg Twice Daily, 400 μg Twice Daily) vs. Placebo When Administered to Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Aclidinium bromide dose, inhaled, for 12 weeks of treatment	Drug: Aclidinium bromide; Aclidinium bromide 200 μg, oral inhalation twice per day for 12 weeks of treatment
Experimental: 2 Aclidinium bromide dose, inhaled, for 12 weeks of treatment	Drug: Aclidinium bromide; Aclidinium bromide 400 μg, oral inhalation twice per day for 12 weeks of treatment
Placebo Comparator: 3 Inhaled placebo for 12 weeks	Drug: Placebo; Dose-matched placebo, oral inhalation twice per day for 12 weeks of treatment

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1) [Change from Baseline to 12 weeks]

   Change from baseline in trough forced expiratory volume in 1 second before the morning dose of aclidinium bromide, Last Observation Carried Forward (LOCF)

Secondary Outcome Measures

1. Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) [Change from Baseline to 12 weeks]

   Change From Baseline in Peak FEV1 (L) at Week 12, Last Observation Carried Forward (LOCF)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• A diagnosis of stable moderate to severe COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, 2009; postbronchodilator FEV1/FVC < 70%, and postbronchodilator FEV1 ≥ 30% and < 80% predicted

• Current or former cigarette smokers

Exclusion Criteria:

• Patients who have been hospitalized for an acute COPD exacerbation within 3 months before the first visit

• Respiratory tract infection or COPD exacerbation in the 6 weeks before Visit 1

• Patient with any clinically significant respiratory conditions other than COPD, cardiovascular conditions or mental illness

• History or presence of asthma verified from medical records

• Chronic use of oxygen therapy greater than or equal to 15 hours per day

• Patient with uncontrolled infection due to HIV and/or active hepatitis

• Patients with a history of hypersensitivity reaction to inhaled anticholinergics

• Patients with clinically significant cardiovascular conditions, including myocardial infarction during the previous 6 months, newly diagnosed arrhythmia within the previous 3 months, unstable angina, unstable arrhythmia that had required changes in pharmacological therapy or other intervention.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site	Birmingham	Alabama	United States	35209
2	Forest Investigative Site	Jasper	Alabama	United States	35501
3	Forest Investigative Site	Mobile	Alabama	United States	18020
4	Forest Investigative Site	Mesa	Arizona	United States	85210
5	Forest Investigative Site	Phoenix	Arizona	United States	85006
6	Forest Investigative Site	Phoenix	Arizona	United States	85023
7	Forest Investigative Site	Anaheim	California	United States	92801
8	Forest Investigative Site	Encinitas	California	United States	92024
9	Forest Investigative Site	Fresno	California	United States	93726
10	Forest Investigative Site	Fullerton	California	United States	92835
11	Forest Investigative Site	Lakewood	California	United States	90712
12	Forest Investigative Site	Orange	California	United States	92868
13	Forest Investigative Site	Palo Alto	California	United States	94304
14	Forest Investigative Site	Rancho Mirage	California	United States	92270
15	Forest Investigative Site	Sacramento	California	United States	95831
16	Forest Investigative Site	San Diego	California	United States	92103-8415
17	Forest Investigative Site	San Diego	California	United States	92120
18	Forest Investigative Site	Colorado Springs	Colorado	United States	80907
19	Forest Investigative Site	Denver	Colorado	United States	80206
20	Forest Investigative Site	Wheat Ridge	Colorado	United States	80033
21	Forest Investigative Site	Waterbury	Connecticut	United States	06708
22	Forest Investigative Site	Brandon	Florida	United States	33511
23	Forest Investigative Site	Clearwater	Florida	United States	33765
24	Forest Investigative Site	DeLand	Florida	United States	32720
25	Forest Investigative Site	Fort Lauderdale	Florida	United States	33316
26	Forest Investigative Site	Melbourne	Florida	United States	32901
27	Forest Investigative Site	Melbourne	Florida	United States	32935
28	Forest Investigative Site	Ormond Beach	Florida	United States	32174
29	Forest Investigative Site	Panama City	Florida	United States	32405
30	Forest Investigative Site	Pensacola	Florida	United States	32504
31	Forest Investigative Site	Tamarac	Florida	United States	33321
32	Forest Investigative Site	Tampa	Florida	United States	33603
33	Forest Investigative Site	Tampa	Florida	United States	33613
34	Forest Investigative Site	Austell	Georgia	United States	30106
35	Forest Investigative Site	Blue Ridge	Georgia	United States	30513
36	Forest Investigative Site	Duluth	Georgia	United States	30096
37	Forest Investigative Site	Marietta	Georgia	United States	30060
38	Forest Investigative Site	River Forest	Illinois	United States	60305
39	Forest Investigative Site	Skokie	Illinois	United States	60076
40	Forest Investigative Site	South Bend	Indiana	United States	46617
41	Forest Investigative Site	Crescent Springs	Kentucky	United States	41017
42	Forest Investigative Site	Lexington	Kentucky	United States	40504
43	Forest Investigative Site	Lafayette	Louisiana	United States	70503
44	Forest Investigative Site	Bangor	Maine	United States	04401
45	Forest Investigative Site	Baltimore	Maryland	United States	21201
46	Forest Investigative Site	Baltimore	Maryland	United States	21224
47	Forest Investigative Site	Hagerstown	Maryland	United States	21740
48	Forest Investigative Site	North Dartmouth	Massachusetts	United States	02747
49	Forest Investigative Site	Livonia	Michigan	United States	48152
50	Forest Investigative Site	Edina	Minnesota	United States	55435
51	Forest Investigative Site	Minneapolis	Minnesota	United States	55402
52	Forest Investigative Site	Minneapolis	Minnesota	United States	55407
53	Forest Investigative Site	Florissant	Missouri	United States	63033
54	Forest Investigative Site	Saint Charles	Missouri	United States	63301
55	Forest Investigative Site	Billings	Montana	United States	59102
56	Forest Investigative Site	Butte	Montana	United States	59701
57	Forest Investigative Site	Papillion	Nebraska	United States	68046
58	Forest Investigative Site	Berlin	New Jersey	United States	08009
59	Forest Investigative Site	Summit	New Jersey	United States	07901
60	Forest Investigative Site	Brooklyn	New York	United States	11234
61	Forest Investigative Site	Buffalo	New York	United States	14215
62	Forest Investigative Site	Great Neck	New York	United States	11023
63	Forest Investigative Site	Ithaca	New York	United States	14580
64	Forest Investigative Site	New Hyde Park	New York	United States	11040
65	Forest Investigative Site	New York	New York	United States	10004
66	Forest Investigative Site	New York	New York	United States	10016
67	Forest Investigative Site	Asheville	North Carolina	United States	28801
68	Forest Investigative Site	Charlotte	North Carolina	United States	28207
69	Forest Investigative Site	Raleigh	North Carolina	United States	27607
70	Forest Investigative Site	Canton	Ohio	United States	44718
71	Forest Investigative Site	Cincinnati	Ohio	United States	45227
72	Forest Investigative Site	Cincinnati	Ohio	United States	45231
73	Forest Investigative Site	Cincinnati	Ohio	United States	45242
74	Forest Investigative Site	Columbus	Ohio	United States	43215
75	Forest Investigative Site	Toledo	Ohio	United States	43606
76	Forest Investigative Site	Oklahoma City	Oklahoma	United States	73120
77	Forest Investigative Site	Medford	Oregon	United States	97504
78	Forest Investigative Site	Portland	Oregon	United States	97213
79	Forest Investigative Site	Bethlehem	Pennsylvania	United States	18020
80	Forest Investigative Site	Erie	Pennsylvania	United States	16506
81	Forest Investigative Site	Hershey	Pennsylvania	United States	17033
82	Forest Investigative Site	Pittsburgh	Pennsylvania	United States	15243
83	Forest Investigative Site	Upland	Pennsylvania	United States	19013
84	Forest Investigative Site	East Providence	Rhode Island	United States	02914
85	Forest Investigative Site	Johnston	Rhode Island	United States	02919
86	Forest Investigative Site	Charleston	South Carolina	United States	29406
87	Forest Investigative Site	Greenville	South Carolina	United States	29615
88	Forest Investigative Site	Greer	South Carolina	United States	29651
89	Forest Investigative Site	Spartanburg	South Carolina	United States	29303
90	Forest Investigative Site	Nashville	Tennessee	United States	37232-2650
91	Forest Investigative Site	Dallas	Texas	United States	75231
92	Forest Investigative Site	Dallas	Texas	United States	75246
93	Forest Investigative Site	Fort Worth	Texas	United States	76104
94	Forest Investigative Site	Houston	Texas	United States	77024
95	Forest Investigative Site	San Antonio	Texas	United States	78229
96	Forest Investigative Site	Tyler	Texas	United States	75708
97	Forest Investigative Site	Waco	Texas	United States	76712
98	Forest Investigative Site	Midvale	Utah	United States	84047
99	Forest Investigative Site	Richmond	Virginia	United States	23225
100	Forest Investigative Site	Richmond	Virginia	United States	23249
101	Forest Investigative Site	Bellingham	Washington	United States	98225
102	Forest Investigative Site	Spokane	Washington	United States	99204
103	Forest Investigative Site	Tacoma	Washington	United States	98405
104	Forest Investigative Site	Milwaukee	Wisconsin	United States	53209
105	Forest Investigative Site	Saskatoon	Saskatchewan	Canada	S7N 0W8
106	Forest Investigative Site	Edmonton		Canada	T5J 3S9
107	Forest Investigative Site	Hamilton		Canada	L8N 4A6
108	Forest Investigative Site	Kelowna		Canada	V1Y 8E7
109	Forest Investigative Site	Niagara Falls		Canada	L2G 1J4
110	Forest Investigative Site	Sainte-Foy		Canada	G1V 4G5
111	Forest Investigative Site	Toronto		Canada	M5g 1N8
112	Forest Investigative Site	Toronto		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: NCT00891462
• Other Study ID Numbers: LAS-MD-33; ACCORD COPD I
• First Posted: May 1, 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 April to July of 2009 at 106 study sites, (100 in the United States and 6 additional sites in Canada.) A total of 99 study sites randomized patients.
Pre-assignment Detail	From the total of 561 patients randomized, 560 patients received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 559 had at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population.

Arm/Group Title	Placebo	Aclidinium Bromide, 200µg	Aclidinium Bromide, 400µg
Arm/Group Description	Inhaled placebo for 12 weeks	Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Period Title: Overall Study
STARTED	186	185	190
COMPLETED	149	152	166
NOT COMPLETED	37	33	24

Baseline Characteristics

Arm/Group Title	Placebo	Aclidinium Bromide, 200µg	Aclidinium Bromide, 400µg	Total
Arm/Group Description	Inhaled placebo for 12 weeks	Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.	Total of all reporting groups
Overall Participants	186	184	190	560
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.1 (9.2)	63.1 (9.5)	64.9 (9.5)	64.3 (9.4)
Age, Customized (participants) [Number]
≥ 40 to < 60 years	46 24.7%	64 34.8%	44 23.2%	154 27.5%
≥ 60 to < 70 years	85 45.7%	72 39.1%	87 45.8%	244 43.6%
≥ 70 years	55 29.6%	48 26.1%	59 31.1%	162 28.9%
Gender (Count of Participants)
Female	90 48.4%	83 45.1%	90 47.4%	263 47%
Male	96 51.6%	101 54.9%	100 52.6%	297 53%
Region of Enrollment (participants) [Number]
United States	176 94.6%	170 92.4%	177 93.2%	523 93.4%
Canada	10 5.4%	14 7.6%	13 6.8%	37 6.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1)
Description	Change from baseline in trough forced expiratory volume in 1 second before the morning dose of aclidinium bromide, Last Observation Carried Forward (LOCF)
Time Frame	Change from Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Of 561 patients randomized, 560 patients received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 559 had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population. The primary efficacy endpoint was based on ITT population.

Arm/Group Title	Placebo	Aclidinium Bromide, 200µg	Aclidinium Bromide, 400µg
Arm/Group Description	Dose-matched placebo twice per day, inhaled for 12 weeks of treatment	Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Measure Participants	185	184	190
Least Squares Mean (Standard Error) [L]	-0.025 (0.015)	0.062 (0.015)	0.099 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aclidinium Bromide, 200µg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.086
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aclidinium Bromide, 400µg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.124
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1)
Description	Change From Baseline in Peak FEV1 (L) at Week 12, Last Observation Carried Forward (LOCF)
Time Frame	Change from Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Of 561 patients randomized, 560 patients received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 559 had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population. The primary efficacy endpoint was based on ITT population.

Arm/Group Title	Placebo	Aclidinium Bromide, 200 µg	Aclidinium Bromide, 400µg
Arm/Group Description	Dose matched placebo twice per day, inhaled for 12 weeks of treatment	Aclidinium bromide, 200 µg dose, Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Measure Participants	185	184	190
Least Squares Mean (Standard Error) [L]	0.071 (0.016)	0.217 (0.016)	0.263 (0.016)

Adverse Events

Time Frame	Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Arm/Group Title	Placebo		Aclidinium Bromide, 200µg		Aclidinium Bromide, 400µg
Arm/Group Description	Inhaled placebo for 12 weeks		Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment		Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
All Cause Mortality
	Placebo		Aclidinium Bromide, 200µg		Aclidinium Bromide, 400µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Aclidinium Bromide, 200µg		Aclidinium Bromide, 400µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/186 (2.2%)		8/184 (4.3%)		6/190 (3.2%)
Cardiac disorders
Cardiac failure congestive	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Gastrointestinal disorders
Abdominal hernia obstructive	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Colitis ischaemic	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
General disorders
Pyrexia	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Hepatobiliary disorders
Cholecystitis	1/186 (0.5%)		0/184 (0%)		0/190 (0%)
Cholelithiasis	1/186 (0.5%)		0/184 (0%)		0/190 (0%)
Infections and infestations
Lobar pneumonia	1/186 (0.5%)		0/184 (0%)		0/190 (0%)
Pneumonia viral	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Injury, poisoning and procedural complications
Intentional overdose	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Radius fracture	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Ulna fracture	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Musculoskeletal and connective tissue disorders
Still's disease adult onset	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Metastases to central nervous system	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Lung adenocarcinoma	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Nervous system disorders
Loss of consciousness	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Syncope	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Cerebrovascular accident	1/186 (0.5%)		0/184 (0%)		0/190 (0%)
Psychiatric disorders
Suicidal ideation	0/186 (0%)		2/184 (1.1%)		1/190 (0.5%)
Suicide attempt	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Bipolar disorder	0/186 (0%)		2/184 (1.1%)		0/190 (0%)
Depression	0/186 (0%)		2/184 (1.1%)		0/190 (0%)
Substance abuse	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Renal and urinary disorders
Renal failure acute	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/186 (0.5%)		1/184 (0.5%)		3/190 (1.6%)
Acute respiratory failure	0/186 (0%)		0/184 (0%)		2/190 (1.1%)
Bronchitis	0/186 (0%)		1/184 (0.5%)		0/190 (0%)
Vascular disorders
Hypotension	0/186 (0%)		0/184 (0%)		1/190 (0.5%)
Other (Not Including Serious) Adverse Events
	Placebo		Aclidinium Bromide, 200µg		Aclidinium Bromide, 400µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/186 (12.4%)		17/184 (9.2%)		14/190 (7.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	23/186 (12.4%)		17/184 (9.2%)		14/190 (7.4%)

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.