Efficacy, Safety, and Tolerability of aclidinium bromide in the treatment of moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-38) - LAS-MD-38

Study identifier:LAS-MD-38

ClinicalTrials.gov identifier:NCT01045161

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of 2 Doses of Aclidinium Bromide Compared With Placebo for 12 Weeks in Patients with Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease Followed by a 40-Week Evaluation of the higher Aclidinium Bromide Dose

Medical condition

Chronic Obstructive Pulmonary Disease

Phase

Phase 3

Healthy volunteers

Study drug

Aclidinium bromide, Placebo

Sex

All

Actual Enrollment

544

Study type

Interventional

Age

40 Years +

Date

Study Start Date: 01 Mar 2009

Primary Completion Date: 01 Jun 2011

Study Completion Date: 01 Jun 2011

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Forest Investigative Site 1493

Birmingham, AL, United States, 35209

Location

Forest Investigative Site 1419

Birmingham, AL, United States, 35233

Location

Forest Investigative Site 1413

Muscle Shoals, AL, United States, 35662

Location

Forest Investigative Site 1353

Pell City, AL, United States, 35128

Location

Forest Investigative Site 1379

Phoenix, AZ, United States, 85018

Location

Forest Investigative Site 1451

National City, CA, United States, 91950

Location

Forest Investigative Site 1388

Paramount, CA, United States, 90723

Location

Forest Investigative Site 1424

Rolling Hill Estates, CA, United States, 90274

Arms	Assigned Interventions
Experimental: 1 Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks	Drug: Aclidinium bromide Aclidinium bromide 200 μg, oral inhalation twice per day 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks of treatment. Drug: Aclidinium bromide Aclidinium bromide 200 μg, oral inhalation twice per day 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks of treatment.
Experimental: 2 Aclidinium bromide 400 μg dose twice per day, inhaled for 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 400 μg will continue to receive open label 400µg aclidinium bromide for 40 weeks	Drug: Aclidinium bromide Aclidinium bromide 200 μg, oral inhalation twice per day 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks of treatment. Drug: Aclidinium bromide Aclidinium bromide 200 μg, oral inhalation twice per day 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks of treatment.
Placebo Comparator: 3 Dose-match placebo, oral inhalation twice per day for 12 weeks of treatment. At week 12, patients who were on placebo will receive open label 400µg aclidinium bromide for 40 weeks	Drug: Placebo Dose-matched placebo, oral inhalation twice per day for 12 weeks. At week 12, patients who were on placebo will receive open label 400 µg aclidinium bromide for 40 weeks of treatment

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patient recruitment occurred from December of 2009 to June of 2010 at 112 study sites (110 in the United States and 2 additional sites in Canada).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Of these patients, 405 had a baseline and postbaseline assessment for the ITT Population.

Reporting Groups

	Description
Placebo - Part A Placebo to Aclidinium Bromide 400 μg - Part B	Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment. After 12 weeks, patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.
Aclidinium Bromide 200μg to Aclidinium Bromide 400μg	Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment. After 12 weeks, patients who were Aclidinium bromide 200 microgram dose, received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.
Aclidinium Bromide 400μg to Aclidinium Bromide 400μg	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment. After 12 weeks, patients continued to receive Aclidinium bromide, 400 microgram dose as an open-label treatment for an additional 40 weeks

Participant Flow for 2 periods

Period 1: Part A - 12 weeks Double Blind Treatment

	Placebo - Part A Placebo to Aclidinium Bromide 400 μg - Part B	Aclidinium Bromide 200μg to Aclidinium Bromide 400μg	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg
STARTED	182	184	178
COMPLETED	151	155	148
NOT COMPLETED	31	29	30
Withdrawal by Subject	8	12	6
Adverse Event	4	3	8
Lack of Efficacy	6	3	2
COPD Exacerbation	4	1	6
Other Reason	3	3	3
Protocol Violation	3	4	3
Lost to Follow-up	3	3	2

Period 2: Part B - 40 additional weeks open label

	Placebo - Part A Placebo to Aclidinium Bromide 400 μg - Part B	Aclidinium Bromide 200μg to Aclidinium Bromide 400μg	Aclidinium Bromide 400μg to Aclidinium Bromide 400μg
STARTED	147	154	147
COMPLETED	111	118	115
NOT COMPLETED	36	36	32
Withdrawal by Subject	10	7	9
Adverse Event	10	10	7
Lack of Efficacy	3	5	5
COPD Exacerbation	1	5	1
Other Reason	4	2	1
Protocol Violation	3	6	3
Lost to Follow-up	5	1	6

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Baseline characteristics for Part B are based on participant totals of 147, 154 and 147

Reporting Groups

	Description
Placebo Part A / Placebo to Aclidinium Bromide 400μg Part B	Dose-matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment in Part A of the Trial. After week 12 (conclusion of Part A), patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.
Aclidinium Bromide(AB) 200μg Part A / AB 200μg to 400μg Part B	Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment in Part A of the Trial. After week 12 (conclusion of Part A), patients who were on a double-blind, 200 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at a 400 microgram dose for an additional 40 weeks.
Aclidinium bromide(AB) 400μg Part A / AB 400μg to 400μg Part B	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment in Part A of the Trial. After week 12 (conclusion of Part A), patients who were on a double-blind, 400 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at the same 400 microgram dose for an additional 40 weeks.

Baseline Measures

	Placebo Part A / Placebo to Aclidinium Bromide 400μg Part B	Aclidinium Bromide(AB) 200μg Part A / AB 200μg to 400μg Part B	Aclidinium bromide(AB) 400μg Part A / AB 400μg to 400μg Part B	Total
Number of Participants [units: Participants]	182	183	177	542
Age Continuous [units: years] Mean ± Standard Deviation
Part A	61.7 ± 9.3	63.4 ± 8.5	63.2 ± 9.0	62.8 ± 8.9
Part B	61.3 ± 9.1	63.8 ± 8.2	63.1 ± 8.6	62.8 ± 8.7
Age, Customized [units: participants]
≥ 40 to < 60 years - Part A	72	57	57	186
≥ 60 to < 70 years - Part A	72	79	77	228
≥ 70 years - Part A	38	47	43	128
≥ 40 to < 60 years - Part B	60	46	46	152
≥ 60 to < 70 years - Part B	58	67	67	192
≥ 70 years - Part B	29	41	34	104
Gender, Male/Female ^[1] [units: participants]
Female	82	84	88	254
Male	100	99	89	288
Gender, Male/Female ^[2] [units: participants]
Female	63	69	74	206
Male	84	85	73	242
Region of Enrollment ^[3] [units: participants]
United States	180	181	175	536
Canada	2	2	2	6
Region of Enrollment ^[4] [units: participants]
United States	145	152	145	442
Canada	2	2	2	6

Outcome Measures

1. Primary Outcome Measure: Part A: Morning Predose (Trough) forced expiratory volume in 1 second (FEV1) [ Time Frame: Change from baseline (Week 0) to Week 12 ]

Measure Type	Primary
Measure Name	Part A: Morning Predose (Trough) forced expiratory volume in 1 second (FEV1)
Measure 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 (Week 0) to Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of 544 patients randomized, 542 patients received at least 1 dose of double-blind treatment and were included in the Safety Population. Of these patients, 541 had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population.

Reporting Groups

	Description
Placebo	Dose-matched placebo twice per day, inhaled for 12 weeks of treatment.
Aclidinium bromide 200 μg	Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment.
Aclidinium bromide 400 μg	Inhaled Aclidinium bromide 400 μg twice per day for 12 weeks.

Measured Values

	Placebo	Aclidinium bromide 200 μg	Aclidinium bromide 400 μg
Number of Participants Analyzed [units:participants]	182	182	177
Part A: Morning Predose (Trough) forced expiratory volume in 1 second (FEV1) [units: L] Least Squares Mean (Standard Error)	-0.008 (0.015)	0.043 (0.015)	0.064 (0.016)

Statistical Analysis 1 for Part A: Morning Predose (Trough) forced expiratory volume in 1 second (FEV1)

Groups^[1]	Placebo, Aclidinium bromide 200 μg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.019
Other^[5]	0.051
95% Confidence Interval	( 0.01 to 0.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Part A: Morning Predose (Trough) forced expiratory volume in 1 second (FEV1)

Groups^[1]	Placebo, Aclidinium bromide 400 μg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0012
Other^[5]	0.072
95% Confidence Interval	( 0.03 to 0.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Part B: Morning Predose (Trough) FEV1 [ Time Frame: Change from baseline (Week 0) to 52 Weeks ]

Measure Type	Primary
Measure Name	Part B: Morning Predose (Trough) FEV1
Measure Description	Change from Baseline in Morning Pre-dose (trough) Forced Expiratory Volume in 1 Second (FEV1) at Week 52, Lost Observation Carried Forward (LOCF)
Time Frame	Change from baseline (Week 0) to 52 Weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Of these patients, 405 had a baseline and postbaseline assessment for the ITT Population.

Reporting Groups

	Description
Placebo - Aclidinium bromide 400 μg	Dose matched placebo, oral inhalation, twice per day for 12 weeks of treatment. At week 12, patients who were on placebo were switched to open label 400µg aclidinium bromide for 40 weeks
Aclidinium bromide 200 μg - Aclidinium bromide 400 μg	Aclidinium bromide, 200 μg dose, oral inhalation, twice per day for 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg were switched to open label 400µg aclidinium bromide for 40 weeks.
Aclidinium bromide 400 μg - Aclidinium bromide 400 μg	Aclidinium bromide, 400 μg dose, oral inhalation, twice per day for 12 weeks of treatment. At week 12, patients received open label 400µg aclidinium bromide for 40 additional weeks

Measured Values

	Placebo - Aclidinium bromide 400 μg	Aclidinium bromide 200 μg - Aclidinium bromide 400 μg	Aclidinium bromide 400 μg - Aclidinium bromide 400 μg
Number of Participants Analyzed [units:participants]	134	139	132
Part B: Morning Predose (Trough) FEV1 [units: L] Mean (Standard Deviation)	0.045 (0.021)	0.029 (0.020)	0.048 (0.021)

Statistical Analysis 1 for Part B: Morning Predose (Trough) FEV1

Groups^[1]	Placebo - Aclidinium bromide 400 μg, Aclidinium bromide 200 μg - Aclidinium bromide 400 μg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0192
Other^[5]	0.051
95% Confidence Interval	( 0.01 to 0.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Part B: Morning Predose (Trough) FEV1

Groups^[1]	Placebo - Aclidinium bromide 400 μg, Aclidinium bromide 400 μg - Aclidinium bromide 400 μg
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0012
Other^[5]	0.072
95% Confidence Interval	( 0.03 to 0.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Part A: Peak Forced Expiratory volume in 1 second (FEV1) [ Time Frame: Change from baseline (Week 0) to Week 12 ]

Measure Type	Secondary
Measure Name	Part A: Peak Forced Expiratory volume in 1 second (FEV1)
Measure Description	Change from baseline in peak FEV1 at week 12, Last Observation Carried Forward (LOCF)
Time Frame	Change from baseline (Week 0) to Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of 544 patients randomized, 542 patients received at least 1 dose of double-blind treatment and were included in the Safety Population. Of these patients, 541 had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent to Treat (ITT) Population.

Reporting Groups

	Description
Placebo	Dose-matched placebo twice per day, inhaled for 12 weeks of treatment.
Aclidinium bromide 200 μg	Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment.
Aclidinium bromide 400 μg	Inhaled Aclidinium bromide 400 μg twice per day for 12 weeks.

Measured Values

	Placebo	Aclidinium bromide 200 μg	Aclidinium bromide 400 μg
Number of Participants Analyzed [units:participants]	182	182	177
Part A: Peak Forced Expiratory volume in 1 second (FEV1) [units: L] Least Squares Mean (Standard Error)	0.087 (0.018)	0.202 (0.018)	0.212 (0.018)

No statistical analysis provided for Part A: Peak Forced Expiratory volume in 1 second (FEV1)

4. Secondary Outcome Measure: Part B: Peak FEV1 [ Time Frame: Change from baseline (Week 0) to 52 Weeks ]

Measure Type	Secondary
Measure Name	Part B: Peak FEV1
Measure Description	Change from Baseline in Peak FEV1 (L) at Week 52, Last Observation Carried Forward (LOCF)
Time Frame	Change from baseline (Week 0) to 52 Weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
A total of 544 patients were randomized, with 542 in the Part A Safety population. Of the 454 patients who completed Part A, 448 patients continued into Part B, receiving at least 1 dose of open-label treatment, were included in the Part B Safety Population. Of these patients, 405 had a baseline and postbaseline assessment for the ITT Population.

Reporting Groups

	Description
Placebo - Aclidinium bromide 400 μg	Dose matched placebo, oral inhalation twice per day for 12 weeks. At week 12, patients who were on placebo switched to open label 400µg aclidinium bromide for 40 weeks
Aclidinium bromide 200 μg - Aclidinium bromide 400 μg	Aclidinium bromide 200 μg, oral inhalation twice per day for 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg switched to open label 400µg aclidinium bromide for 40 weeks
Aclidinium bromide 400 μg - Aclidinium bromide 400 μg	Aclidinium bromide 400 μg dose, oral inhalation twice per day for 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 400 μg switched to open label 400µg aclidinium bromide for 40 weeks

Measured Values

	Placebo - Aclidinium bromide 400 μg	Aclidinium bromide 200 μg - Aclidinium bromide 400 μg	Aclidinium bromide 400 μg - Aclidinium bromide 400 μg
Number of Participants Analyzed [units:participants]	134	139	132
Part B: Peak FEV1 [units: L] Least Squares Mean (Standard Error)	0.185 (0.023)	0.176 (0.023)	0.172 (0.023)

No statistical analysis provided for Part B: Peak FEV1

Serious Adverse Events

Time Frame	Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Additional Description	No text entered.

Reporting Groups

	Description
Placebo - Part A	Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment.
Aclidinium bromide 200 μg - Part A	Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment.
Aclidinium bromide 400 μg - Part A	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment.
Placebo to Aclidinium Bromide 400 μg - Part B	After week 12 (conclusion of Part A), patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.
Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B	Part B - After week 12 (conclusion of Part A), patients who were on a double-blind, 200 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at a 400 microgram dose for an additional 40 weeks.
Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B	After week 12 (conclusion of Part A), patients who were on a double-blind, 400 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at the same 400 microgram dose for an additional 40 weeks.

Serious Adverse Events

Placebo - Part A

Aclidinium bromide 200 μg - Part A

Aclidinium bromide 400 μg - Part A

Placebo to Aclidinium Bromide 400 μg - Part B

Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B

Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B

Total, serious adverse events

# participants affected / at risk

12/182 (6.59%)

11/183 (6.01%)

8/177 (4.52%)

15/147 (10.20%)

20/154 (12.99%)

14/147 (9.52%)

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

6/182 (3.30%)

5/183 (2.73%)

5/177 (2.82%)

4/147 (2.72%)

7/154 (4.55%)

3/147 (2.04%)

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

2/147 (1.36%)

2/154 (1.30%)

0/147 (0.00%)

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

2/147 (1.36%)

0/154 (0.00%)

0/147 (0.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

1/147 (0.68%)

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

1/147 (0.68%)

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

2/154 (1.30%)

0/147 (0.00%)

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

1/147 (0.68%)

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

1/154 (0.65%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pneumonia¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

1/154 (0.65%)

0/147 (0.00%)

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Cardiac disorders

Cardio-respiratory arrest¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

1/177 (0.56%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Nervous system disorders

Carotid artery stenosis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Injury, poisoning and procedural complications

Cervical vertebral fracture¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Infections and infestations

Clostridium difficile colitis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Reproductive system and breast disorders

Cystocele¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Metabolism and nutrition disorders

Diabetes mellitus inadequate control¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Injury, poisoning and procedural complications

Femoral neck fracture¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Injury, poisoning and procedural complications

Haematoma¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal cancer¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Infections and infestations

Lobar pneumonia¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Nervous system disorders

Lumbar radiculopathy¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Psychiatric disorders

Mental status changes¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Nervous system disorders

Migraine¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Cardiac disorders

Myocardial ischaemia¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Infections and infestations

Osteomyelitis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Infections and infestations

Osteomyelitis bacterial¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Vascular disorders

Peripheral arterial occlusive disease¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Respiratory, thoracic and mediastinal disorders

Pulmonary mass¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cell carcinoma¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Renal and urinary disorders

Renal failure acute¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Infections and infestations

Staphylococcal bacteraemia¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Infections and infestations

Staphylococcal sepsis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Infections and infestations

Staphylococcal skin infection¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Nervous system disorders

Subarachnoid haemorrhage¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Reproductive system and breast disorders

Uterine haemorrhage¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

1/147 (0.68%)

0/154 (0.00%)

0/147 (0.00%)

Nervous system disorders

VIIth nerve paralysis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

1/147 (0.68%)

Reproductive system and breast disorders

Vulvar dysplasia¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

1/154 (0.65%)

0/147 (0.00%)

Vascular disorders

Aortic aneurysm¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

1/177 (0.56%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Gastrointestinal disorders

Gastrenteritis salmonella¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

1/177 (0.56%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pseudomonas bronchitis¹,^†

# participants affected / at risk

0/182 (0.00%)

0/183 (0.00%)

1/177 (0.56%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Psychiatric disorders

Agitated depression¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/182 (0.00%)

2/183 (1.09%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Reproductive system and breast disorders

Benign prostatic hyperplasia¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Hepatobiliary disorders

Cholangitis¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Hepatobiliary disorders

Cholecystitis acute¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

General disorders and administration site conditions

Death¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Gastrointestinal disorders

Duodenal ulcer¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Gastrointestinal disorders

Gastrointestinal haemorrhage¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Injury, poisoning and procedural complications

Joint injury¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Ear and labyrinth disorders

Labyrinthitis¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Infections and infestations

Lobar pneumonia¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Lung adenocarcinoma¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Respiratory, thoracic and mediastinal disorders

Respiratory acidosis¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Psychiatric disorders

Suicidal ideation¹,^†

# participants affected / at risk

1/182 (0.55%)

0/183 (0.00%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

Vascular disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

0/182 (0.00%)

1/183 (0.55%)

0/177 (0.00%)

0/147 (0.00%)

0/154 (0.00%)

0/147 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA (13.1)

Other Adverse Events

Time Frame	Adverse Event reporting began in December of 2009 and concluded in July of 2011 at 112 study sites (110 in the United States and 2 additional sites in Canada).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo - Part A	Dose matched placebo, twice per day, oral inhalation for 12 weeks of double-blind treatment.
Aclidinium bromide 200 μg - Part A	Aclidinium bromide 200 microgram dose, oral inhalation, twice per day for 12 weeks of double-blind treatment.
Aclidinium bromide 400 μg - Part A	Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 12 weeks of double-blind treatment.
Placebo to Aclidinium Bromide 400 μg - Part B	After week 12 (conclusion of Part A), patients who were on placebo received open-label Aclidinium Bromide, 400 microgram dose, for an additional 40 weeks.
Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B	Part B - After week 12 (conclusion of Part A), patients who were on a double-blind, 200 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at a 400 microgram dose for an additional 40 weeks.
Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B	After week 12 (conclusion of Part A), patients who were on a double-blind, 400 microgram Aclidinium Bromide dose, were switched to open-label Aclidinium Bromide at the same 400 microgram dose for an additional 40 weeks.

Other Adverse Events

Placebo - Part A

Aclidinium bromide 200 μg - Part A

Aclidinium bromide 400 μg - Part A

Placebo to Aclidinium Bromide 400 μg - Part B

Aclidinium Bromide 200μg to Aclidinium Bromide 400μg - Part B

Aclidinium Bromide 400μg to Aclidinium Bromide 400μg - Part B

Total, other (not including serious) adverse events

# participants affected / at risk

22/182 (12.09%)

20/183 (10.93%)

28/177 (15.82%)

37/147 (25.17%)

50/154 (32.47%)

52/147 (35.37%)

Respiratory, thoracic and mediastinal disorders

COPD exacerbation¹,^†

# participants affected / at risk

21/182 (11.54%)

16/183 (8.74%)

23/177 (12.99%)

24/147 (16.33%)

35/154 (22.73%)

41/147 (27.89%)

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

1/182 (0.55%)

3/183 (1.64%)

3/177 (1.69%)

9/147 (6.12%)

9/154 (5.84%)

8/147 (5.44%)

Respiratory, thoracic and mediastinal disorders

Nasopharyngitis¹,^†

# participants affected / at risk

0/182 (0.00%)

2/183 (1.09%)

2/177 (1.13%)

6/147 (4.08%)

9/154 (5.84%)

6/147 (4.08%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA (13.1)

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	AstraZeneca Clinical
Organization:	Study Information Center
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

las-md-38-synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical

1-877-2409479

information.center@astrazeneca.com

Investigators

Principal Investigator

Esther Garcia

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Forest Investigative Site 1493

Forest Investigative Site 1419

Forest Investigative Site 1413

Forest Investigative Site 1353

Forest Investigative Site 1379

Forest Investigative Site 1451

Forest Investigative Site 1388

Forest Investigative Site 1424

las-md-38-synopsis

Trial Results Summaries