Trial Outcomes & Findings for Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-33) (NCT NCT00891462)

Last Updated: 2017-01-06

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

561 participants

Primary outcome timeframe

Change from Baseline to 12 weeks

Results posted on

2017-01-06

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Inhaled placebo for 12 weeks	Aclidinium Bromide, 200µg Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Overall Study STARTED	186	185	190
Overall Study COMPLETED	149	152	166
Overall Study NOT COMPLETED	37	33	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Inhaled placebo for 12 weeks	Aclidinium Bromide, 200µg Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Overall Study Withdrawal by Subject	9	6	7
Overall Study Adverse Event	7	8	7
Overall Study Lack of Efficacy	10	5	1
Overall Study COPD exacerbation	7	4	1
Overall Study Other Reason	2	5	3
Overall Study Protocol Violation	2	1	3
Overall Study Inclusion/exclusion criteria	0	2	2
Overall Study Lost to Follow-up	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=186 Participants Inhaled placebo for 12 weeks	Aclidinium Bromide, 200µg n=184 Participants Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg n=190 Participants Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.	Total n=560 Participants Total of all reporting groups
Age, Continuous	65.1 years STANDARD_DEVIATION 9.2 • n=5 Participants	63.1 years STANDARD_DEVIATION 9.5 • n=7 Participants	64.9 years STANDARD_DEVIATION 9.5 • n=5 Participants	64.3 years STANDARD_DEVIATION 9.4 • n=4 Participants
Age, Customized ≥ 40 to < 60 years	46 participants n=5 Participants	64 participants n=7 Participants	44 participants n=5 Participants	154 participants n=4 Participants
Age, Customized ≥ 60 to < 70 years	85 participants n=5 Participants	72 participants n=7 Participants	87 participants n=5 Participants	244 participants n=4 Participants
Age, Customized ≥ 70 years	55 participants n=5 Participants	48 participants n=7 Participants	59 participants n=5 Participants	162 participants n=4 Participants
Gender Female	90 Participants n=5 Participants	83 Participants n=7 Participants	90 Participants n=5 Participants	263 Participants n=4 Participants
Gender Male	96 Participants n=5 Participants	101 Participants n=7 Participants	100 Participants n=5 Participants	297 Participants n=4 Participants
Region of Enrollment United States	176 participants n=5 Participants	170 participants n=7 Participants	177 participants n=5 Participants	523 participants n=4 Participants
Region of Enrollment Canada	10 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	37 participants n=4 Participants

PRIMARY outcome

Timeframe: Change from Baseline to 12 weeks

Population: 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.

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

Outcome measures

Outcome measures
Measure	Placebo n=185 Participants Dose-matched placebo twice per day, inhaled for 12 weeks of treatment	Aclidinium Bromide, 200µg n=184 Participants Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg n=190 Participants Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1)	-0.025 L Standard Error 0.015	0.062 L Standard Error 0.015	0.099 L Standard Error 0.015

SECONDARY outcome

Timeframe: Change from Baseline to 12 weeks

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

Outcome measures

Outcome measures
Measure	Placebo n=185 Participants Dose-matched placebo twice per day, inhaled for 12 weeks of treatment	Aclidinium Bromide, 200µg n=184 Participants Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg n=190 Participants Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1)	0.071 L Standard Error 0.016	0.217 L Standard Error 0.016	0.263 L Standard Error 0.016

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 23 other events

Deaths: 0 deaths

Aclidinium Bromide, 200µg

Serious events: 8 serious events

Other events: 17 other events

Deaths: 0 deaths

Aclidinium Bromide, 400µg

Serious events: 6 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=186 participants at risk Inhaled placebo for 12 weeks	Aclidinium Bromide, 200µg n=184 participants at risk Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg n=190 participants at risk Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	12.4% 23/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	9.2% 17/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	7.4% 14/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.

Additional Information

AstraZeneca Clinical

Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=186 participants at risk Inhaled placebo for 12 weeks	Aclidinium Bromide, 200µg n=184 participants at risk Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment	Aclidinium Bromide, 400µg n=190 participants at risk Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.54% 1/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	1.6% 3/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	1.1% 2/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Cardiac disorders Cardiac failure congestive	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Vascular disorders Hypotension	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Nervous system disorders Loss of consciousness	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Renal and urinary disorders Renal failure acute	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Psychiatric disorders Suicidal ideation	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	1.1% 2/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Psychiatric disorders Suicide attempt	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Nervous system disorders Syncope	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.53% 1/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Gastrointestinal disorders Abdominal hernia obstructive	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Psychiatric disorders Bipolar disorder	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	1.1% 2/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Nervous system disorders Cerebrovascular accident	0.54% 1/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Hepatobiliary disorders Cholecystitis	0.54% 1/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Hepatobiliary disorders Cholelithiasis	0.54% 1/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Psychiatric disorders Depression	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	1.1% 2/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Infections and infestations Lobar pneumonia	0.54% 1/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Infections and infestations Pneumonia viral	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
General disorders Pyrexia	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Musculoskeletal and connective tissue disorders Still's disease adult onset	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Psychiatric disorders Substance abuse	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/186 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.54% 1/184 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.	0.00% 0/190 • Adverse events reporting occurred from April 28th, 2009 to December 3rd, 2009 at 99 study sites.