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 extension study is to evaluate the long-term safety, tolerability, and efficacy of inhaled aclidinium bromide at two dose levels in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This study will be 54 weeks in duration; a 52-week double-blind treatment period and 2 week follow-up phone call, following a 12 week lead-in study. All patients will be randomized from the lead-in study at one of two doses of aclidinium.
Interventions
Aclidinium bromide 200 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
* Completion of a lead-in study (NCT00891462)
Exclusion criteria
* Use or anticipated use of any medication prohibited in this study * Evidence of abnormal clinical laboratory values, vital signs, or electrocardiographic (ECG) results or the presence of abnormities in physical examination findings * The presence of anti-cholinergic effects (eg, dry mouth, urinary retention, narrow angle glaucoma) * QTcB of \>500 msec on both the pre-dose and post-dose ECG * Women who are pregnant, intend to become pregnant, or are breast-feeding * A life expectancy of less than 1 year * Noncompliance with IP dosing and/or attending clinic visits during the lead-in study * Significant interruption of double-blind therapy during the transition from the lead-in study into the extension study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | Change from baseline (visit 2 of lead-in study LAS-MD-33) to 52 weeks | Change From Baseline (Visit 2 of lead-in Study NCT00891462, \[LAS-MD-33\]) to Week 52 (Week 64 From Start of NCT00891462, \[LAS-MD-33\]) in Morning Predose (Trough) FEV1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peak FEV1 | 52 weeks | Change From Baseline (Visit 2 of study NCT00891462, \[LAS-MD-33\])in Peak FEV1 in liters at Week 52 (Week 64 from the start of NCT00891462, \[LAS-MD-33\]). |
Countries
Canada, United States
Participant flow
Recruitment details
Patient recruitment occurred from August of 2009 to March of 2010 and was by invitation only to patients who had completed study NCT00891462 (LAS-MD-33). In total, there were 77 individual study sites, 71 in the United States and 6 additional sites in Canada.
Pre-assignment details
From the total of 291 patients enrolled, 289 patients (99.3%) received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 246 (84.5%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the Intent To Treat (ITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Bromide 200 μg Aclidinium bromide, 200 microgram dose, oral inhalation twice per day for 52 weeks of treatment. | 137 |
| Aclidinium Bromide 400 μg Aclidinium bromide, 400 microgram dose, oral inhalation twice per day for 52 weeks of treatment. | 152 |
| Total | 289 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 12 |
| Overall Study | COPD Exacerbation | 4 | 2 |
| Overall Study | Inclusion/Exclusion Criteria | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 6 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other Reason | 3 | 1 |
| Overall Study | Protocol Violation | 4 | 7 |
| Overall Study | Withdrawal by Subject | 12 | 19 |
Baseline characteristics
| Characteristic | Aclidinium Bromide 200 μg | Aclidinium Bromide 400 μg | Total |
|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 10.1 | 64.4 years STANDARD_DEVIATION 10 | 63.9 years STANDARD_DEVIATION 9.9 |
| Age, Customized ≥ 40 to < 60 years | 49 participants | 40 participants | 89 participants |
| Age, Customized ≥ 60 to < 70 years | 51 participants | 67 participants | 118 participants |
| Age, Customized ≥ 70 years | 37 participants | 45 participants | 82 participants |
| Gender Female | 63 Participants | 76 Participants | 139 Participants |
| Gender Male | 74 Participants | 76 Participants | 150 Participants |
| Region of Enrollment Canada | 9 participants | 14 participants | 23 participants |
| Region of Enrollment United States | 128 participants | 138 participants | 266 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 44 | 63 / 93 | 28 / 46 | 64 / 106 |
| serious Total, serious adverse events | 7 / 44 | 13 / 93 | 7 / 46 | 13 / 106 |
Outcome results
Primary
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)
Change From Baseline (Visit 2 of lead-in Study NCT00891462, \[LAS-MD-33\]) to Week 52 (Week 64 From Start of NCT00891462, \[LAS-MD-33\]) in Morning Predose (Trough) FEV1
Time frame: Change from baseline (visit 2 of lead-in study LAS-MD-33) to 52 weeks
Population: From the total of 291 patients enrolled, 289 patients (99.3%) received at least 1 dose of double-blind treatment and therefore were included in the Safety Population. Of these patients, 246 (84.5%) had a baseline and at least 1 postbaseline FEV1 assessment and qualified for the ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Aclidinium Bromide 200 μg | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | -0.035 L | Standard Error 0.04 |
| Aclidinium Bromide 200 μg - Aclidinium Bromide 200 μg | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.069 L | Standard Error 0.028 |
| Placebo - Aclidinium Bromide 400 μg | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.069 L | Standard Error 0.037 |
| Aclidinium Bromide 400 μg - Aclidinium Bromide 400 μg | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | 0.056 L | Standard Error 0.025 |
Secondary
Change From Baseline in Peak FEV1
Change From Baseline (Visit 2 of study NCT00891462, \[LAS-MD-33\])in Peak FEV1 in liters at Week 52 (Week 64 from the start of NCT00891462, \[LAS-MD-33\]).
Time frame: 52 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Aclidinium Bromide 200 μg | Change From Baseline in Peak FEV1 | 0.111 L | Standard Error 0.04 |
| Aclidinium Bromide 200 μg - Aclidinium Bromide 200 μg | Change From Baseline in Peak FEV1 | 0.213 L | Standard Error 0.028 |
| Placebo - Aclidinium Bromide 400 μg | Change From Baseline in Peak FEV1 | 0.222 L | Standard Error 0.038 |
| Aclidinium Bromide 400 μg - Aclidinium Bromide 400 μg | Change From Baseline in Peak FEV1 | 0.219 L | Standard Error 0.025 |