Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, Emphysema, Airflow Obstruction, Chronic, Chronic Airflow Obstruction, Chronic Obstructive Airway Disease, Chronic Obstructive Lung Disease
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.
Interventions
Aclidinium bromide 200 μg, oral inhalation twice per day for 12 weeks of treatment
DRUGPlacebo
Dose-matched placebo, oral inhalation twice per day for 12 weeks of treatment
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Canada, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Inhaled placebo for 12 weeks | 186 |
| Aclidinium Bromide, 200µg Aclidinium bromide, 200 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment | 184 |
| Aclidinium Bromide, 400µg Aclidinium bromide 400 microgram dose. Oral inhalation, twice per day, for 12 weeks of treatment. | 190 |
| Total | 560 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 8 | 7 |
| Overall Study | COPD exacerbation | 7 | 4 | 1 |
| Overall Study | Inclusion/exclusion criteria | 0 | 2 | 2 |
| Overall Study | Lack of Efficacy | 10 | 5 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 |
| Overall Study | Other Reason | 2 | 5 | 3 |
| Overall Study | Protocol Violation | 2 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 9 | 6 | 7 |
Baseline characteristics
| Characteristic | Placebo | Aclidinium Bromide, 200µg | Aclidinium Bromide, 400µg | Total |
|---|---|---|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 9.2 | 63.1 years STANDARD_DEVIATION 9.5 | 64.9 years STANDARD_DEVIATION 9.5 | 64.3 years STANDARD_DEVIATION 9.4 |
| Age, Customized ≥ 40 to < 60 years | 46 participants | 64 participants | 44 participants | 154 participants |
| Age, Customized ≥ 60 to < 70 years | 85 participants | 72 participants | 87 participants | 244 participants |
| Age, Customized ≥ 70 years | 55 participants | 48 participants | 59 participants | 162 participants |
| Gender Female | 90 Participants | 83 Participants | 90 Participants | 263 Participants |
| Gender Male | 96 Participants | 101 Participants | 100 Participants | 297 Participants |
| Region of Enrollment Canada | 10 participants | 14 participants | 13 participants | 37 participants |
| Region of Enrollment United States | 176 participants | 170 participants | 177 participants | 523 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 186 | 17 / 184 | 14 / 190 |
| serious Total, serious adverse events | 4 / 186 | 8 / 184 | 6 / 190 |
Outcome results
Primary
Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1)
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
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | -0.025 L | Standard Error 0.015 |
| Aclidinium Bromide, 200µg | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.062 L | Standard Error 0.015 |
| Aclidinium Bromide, 400µg | Change From Baseline in Morning Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.099 L | Standard Error 0.015 |
p-value: <0.000195% CI: [0.05, 0.13]ANCOVA
p-value: <0.000195% CI: [0.08, 0.16]ANCOVA
Secondary
Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1)
Change From Baseline in Peak FEV1 (L) at Week 12, Last Observation Carried Forward (LOCF)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) | 0.071 L | Standard Error 0.016 |
| Aclidinium Bromide, 200µg | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) | 0.217 L | Standard Error 0.016 |
| Aclidinium Bromide, 400µg | Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) | 0.263 L | Standard Error 0.016 |