Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, 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 evaluate the safety, tolerability and efficacy of inhaled aclidinium bromide at two dose levels in patients with moderate to severe, stable chronic obstructive pulmonary disease. The study will be 56 weeks in duration; a 2-week rin-in period, a 52-week treatment period and a 2-week follow up phone call. All patients will be randomized to one of two doses of aclidinium bromide.
Interventions
DRUGAclidinium Bromide 200 µg
aclidinium bromide 200 μg, oral inhalation twice per day for 52 weeks of treatment
DRUGAclidinium Bromide 400 µg
aclidinium bromide 400 μg, oral inhalation twice per day for 52 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, 2010; 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 (Trough) Forced Expiratory Volume in One Second (FEV1) | From baseline to 52 weeks | Change From Baseline in Morning Predose (Trough) FEV1 in liters at Week 52. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peak FEV1 | 52 weeks | Change From Baseline in Peak FEV1 in liters at Week 52. |
Countries
Canada, United States
Participant flow
Recruitment details
Patient recruitment occurred from November of 2009 to April of 2010 at 109 study sites (106 sites in the United States and 3 additional sites in Canada). A total of 97 study sites randomized patients (94 in the United States and 3 in Canada).
Pre-assignment details
A 2-week run-in period was used to assess the stability of patients' disease and to establish each patient's baseline characteristics. The run-in period was followed by a 52-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Bromide 200µg Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment. | 311 |
| Aclidinium Bromide 400µg Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment. | 291 |
| Total | 602 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 20 |
| Overall Study | COPD exacerbation | 9 | 8 |
| Overall Study | Lack of Efficacy | 23 | 12 |
| Overall Study | Lost to Follow-up | 18 | 12 |
| Overall Study | Other Reason | 7 | 14 |
| Overall Study | Protocol Violation | 11 | 16 |
| Overall Study | Terminated by Sponsor | 22 | 21 |
| Overall Study | Withdrawal by Subject | 21 | 28 |
Baseline characteristics
| Characteristic | Aclidinium Bromide 200µg | Aclidinium Bromide 400µg | Total |
|---|---|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 9.5 | 64.2 years STANDARD_DEVIATION 9.9 | 63.6 years STANDARD_DEVIATION 9.7 |
| Age, Customized ≥ 40 to < 60 years | 113 participants | 96 participants | 209 participants |
| Age, Customized ≥ 60 to < 70 years | 115 participants | 99 participants | 214 participants |
| Age, Customized ≥ 70 years | 83 participants | 96 participants | 179 participants |
| Region of Enrollment Canada | 6 participants | 7 participants | 13 participants |
| Region of Enrollment United States | 305 participants | 284 participants | 589 participants |
| Sex: Female, Male Female | 127 Participants | 124 Participants | 251 Participants |
| Sex: Female, Male Male | 184 Participants | 167 Participants | 351 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 60 / 311 | 58 / 291 |
| serious Total, serious adverse events | 29 / 311 | 29 / 291 |
Outcome results
Primary
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)
Change From Baseline in Morning Predose (Trough) FEV1 in liters at Week 52.
Time frame: From baseline to 52 weeks
Population: Of 605 patients randomized, 602 patients (99.5%) received at least 1 dose of double-blind treatment and were included in the Safety Population. Of these 602 patients, 600 (99.2%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the ITT Population. A decision to terminate one site was made before unblinding of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200µg | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.034 L | Standard Error 0.015 |
| Aclidinium Bromide 400µg | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.072 L | Standard Error 0.015 |
Secondary
Change From Baseline in Peak FEV1
Change From Baseline in Peak FEV1 in liters at Week 52.
Time frame: 52 weeks
Population: Of 605 patients randomized, 602 patients (99.5%) received at least 1 dose of double-blind treatment and were included in the Safety Population. Of these 602 patients, 600 (99.2%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the ITT Population. A decision to terminate one site was made before unblinding of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200µg | Change From Baseline in Peak FEV1 | 0.185 L | Standard Error 0.015 |
| Aclidinium Bromide 400µg | Change From Baseline in Peak FEV1 | 0.214 L | Standard Error 0.015 |