Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Lung function, Exacerbations, Quality of Life
Brief summary
To evaluate the efficacy and safety of LAS 34273 compared to placebo in patients with moderate to severe COPD during one year of treatment.
Interventions
Aclidinium bromide 200 μg once-daily via inhalation by the Eklira Genuair® inhaler: 1 puff in the morning for 52 weeks
DRUGPlacebo
Placebo once-daily via inhalation: 1 puff in the morning for 52 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females aged ≥ 40 years with a clinical diagnosis of moderate to severe stable COPD
Exclusion criteria
* History or current diagnosis of asthma, recent respiratory tract infection or acute COPD exacerbation, life expectancy of less than 1 year, known symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 (L) at 28 Weeks on Treatment | 28 weeks | Trough FEV1 (mean FEV1 value of the two highest FEV1 readings measured at 23 and 24 hours after inhalation) at 28 weeks |
| Trough FEV1 (L) at 12 Weeks on Treatment | 12 weeks | Trough FEV1 (mean FEV1 value of the two highest FEV1 readings measured at 23 and 24 hours after inhalation) at 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Moderate or Severe COPD Exacerbation at 52 Weeks on Treatment | 52 weeks | Time to first moderate or severe exacerbation: Increase of COPD symptoms during at least 2 consecutive days, treated with antibiotics and/or systemic corticosteroids or an increase in dose of systemic corticosteroids, or leading to hospitalisation. |
| Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at 52 Weeks on Treatment | 52 weeks | Percentage of patients who achieved a clinically relevant improvement in health-related quality of life at 52 weeks, as measured by at least a 4-unit decrease from baseline in St George's Respiratory Questionnaire (SGRQ) total score |
Countries
Argentina, Australia, Canada, Mexico, New Zealand, South Africa, United States
Participant flow
Recruitment details
This study was conducted in a total of 119 enrolling sites: 72 sites in the United States, 13 sites in Argentina, 13 sites in Australia, 7 sites in Canada, 2 sites in Mexico, 3 sites in New Zealand and 9 sites in South Africa. The first patient was screened in August 2006 and the last patient visit was in June 2008.
Pre-assignment details
Following a screening visit, patients entered a 14-day run-in period during which they used inhaled salbutamol on an as needed basis. Patients also stopped taking any other COPD medications prohibited by the study protocol. The 14-day run-in period was used to assess the stability of disease and established the patient's baseline characteristics.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Bromide 200 μg Once-daily Aclidinium bromide 200 μg once-daily by inhalation | 600 |
| Placebo Placebo by inhalation | 204 |
| Total | 804 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 29 | 13 |
| Overall Study | COPD exacerbation | 22 | 10 |
| Overall Study | Lack of Efficacy | 34 | 36 |
| Overall Study | Lost to Follow-up | 11 | 6 |
| Overall Study | Non-fulfilment of inclusion/exclusion | 4 | 0 |
| Overall Study | Other | 6 | 1 |
| Overall Study | Protocol Violation | 8 | 3 |
| Overall Study | Withdrawal by Subject | 40 | 17 |
Baseline characteristics
| Characteristic | Placebo | Aclidinium Bromide 200 μg Once-daily | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 119 Participants | 308 Participants | 427 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants | 292 Participants | 377 Participants |
| Age, Continuous | 65.2 years STANDARD_DEVIATION 8.6 | 65.1 years STANDARD_DEVIATION 8.6 | 65.2 years STANDARD_DEVIATION 8.6 |
| Gender Female | 80 Participants | 217 Participants | 297 Participants |
| Gender Male | 124 Participants | 383 Participants | 507 Participants |
| Region of Enrollment Argentina | 42 participants | 122 participants | 164 participants |
| Region of Enrollment Australia | 25 participants | 70 participants | 95 participants |
| Region of Enrollment Canada | 10 participants | 33 participants | 43 participants |
| Region of Enrollment Mexico | 2 participants | 7 participants | 9 participants |
| Region of Enrollment New Zealand | 4 participants | 12 participants | 16 participants |
| Region of Enrollment South Africa | 20 participants | 61 participants | 81 participants |
| Region of Enrollment United States | 101 participants | 295 participants | 396 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 445 / 600 | 136 / 204 |
| serious Total, serious adverse events | 62 / 600 | 23 / 204 |
Outcome results
Primary
Trough FEV1 (L) at 12 Weeks on Treatment
Trough FEV1 (mean FEV1 value of the two highest FEV1 readings measured at 23 and 24 hours after inhalation) at 12 weeks
Time frame: 12 weeks
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and had at least the baseline and one post-baseline value available for the primary efficacy variable.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200 μg Once-daily | Trough FEV1 (L) at 12 Weeks on Treatment | 1.233 Liters | Standard Error 0.007 |
| Placebo | Trough FEV1 (L) at 12 Weeks on Treatment | 1.171 Liters | Standard Error 0.012 |
Primary
Trough FEV1 (L) at 28 Weeks on Treatment
Trough FEV1 (mean FEV1 value of the two highest FEV1 readings measured at 23 and 24 hours after inhalation) at 28 weeks
Time frame: 28 weeks
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and had at least the baseline and one post-baseline value available for the primary efficacy variable.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200 μg Once-daily | Trough FEV1 (L) at 28 Weeks on Treatment | 1.220 Liters | Standard Error 0.008 |
| Placebo | Trough FEV1 (L) at 28 Weeks on Treatment | 1.162 Liters | Standard Error 0.014 |
Secondary
Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at 52 Weeks on Treatment
Percentage of patients who achieved a clinically relevant improvement in health-related quality of life at 52 weeks, as measured by at least a 4-unit decrease from baseline in St George's Respiratory Questionnaire (SGRQ) total score
Time frame: 52 weeks
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and had at least the baseline and one post-baseline value available for the primary efficacy variable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aclidinium Bromide 200 μg Once-daily | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at 52 Weeks on Treatment | Yes (% Patients with 4-unit decrease) | 39.0 Percentage of Patients |
| Aclidinium Bromide 200 μg Once-daily | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at 52 Weeks on Treatment | No (% Patients without 4-unit decrease) | 61.0 Percentage of Patients |
| Placebo | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at 52 Weeks on Treatment | Yes (% Patients with 4-unit decrease) | 32.8 Percentage of Patients |
| Placebo | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at 52 Weeks on Treatment | No (% Patients without 4-unit decrease) | 67.2 Percentage of Patients |
Secondary
Time to First Moderate or Severe COPD Exacerbation at 52 Weeks on Treatment
Time to first moderate or severe exacerbation: Increase of COPD symptoms during at least 2 consecutive days, treated with antibiotics and/or systemic corticosteroids or an increase in dose of systemic corticosteroids, or leading to hospitalisation.
Time frame: 52 weeks
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and had at least the baseline and one post-baseline value available for the primary efficacy variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aclidinium Bromide 200 μg Once-daily | Time to First Moderate or Severe COPD Exacerbation at 52 Weeks on Treatment | NA Days |
| Placebo | Time to First Moderate or Severe COPD Exacerbation at 52 Weeks on Treatment | NA Days |