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 via 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 | Week 28 | Trough FEV1 (mean of two highest FEV1 values assessed at 23 and 24 hours after inhalation) at 28 weeks |
| Trough Forced Expiratory Volume in the First Second (FEV1) (L) at 12 Weeks on Treatment | Week 12 | Trough FEV1 (mean of two highest FEV1 values assessed 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 | Week 52 | 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
Andorra, Austria, Belgium, Bulgaria, Czechia, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, Russia, Spain, United Kingdom
Participant flow
Recruitment details
The study was conducted in 132 sites: 1 in Andorra, 5 in Austria, 4 in Belgium, 10 in Bulgaria, 8 in the Czech Republic, 3 in Denmark, 9 in France, 10 in Germany, 8 in Hungary, 6 in Italy, 4 in Netherlands, 9 in Poland, 9 in Romania, 25 in Russia, 8 in Spain, 13 in the UK. First patient was screened in Aug 2006 and last patient visit was May 2008.
Pre-assignment details
Following a screening visit, patients entered a 14-day run-in period during which they used inhaled salbutamol administered via a pressurised metered dose inhaler (pMDI) as rescue medication on an as needed basis. The 14-day run-in period was used to assess the stability of each patient's disease and baseline characteristics.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Bromide 200 μg Once-daily Aclidinium bromide 200 μg once-daily by inhalation | 627 |
| Placebo Placebo by inhalation | 216 |
| Total | 843 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 24 | 13 |
| Overall Study | COPD exacerbation | 13 | 7 |
| Overall Study | Lack of Efficacy | 12 | 8 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Non-fulfilment of entry criteria | 1 | 0 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Protocol Violation | 6 | 1 |
| Overall Study | Withdrawal by Subject | 29 | 16 |
Baseline characteristics
| Characteristic | Aclidinium Bromide 200 μg Once-daily | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 249 Participants | 331 Participants | 82 Participants |
| Age, Categorical Between 18 and 65 years | 378 Participants | 512 Participants | 134 Participants |
| Age, Continuous | 62.6 years STANDARD_DEVIATION 8.2 | 62.4 years STANDARD_DEVIATION 8.2 | 61.9 years STANDARD_DEVIATION 8.3 |
| Gender Female | 139 Participants | 180 Participants | 41 Participants |
| Gender Male | 488 Participants | 663 Participants | 175 Participants |
| Region of Enrollment Andorra | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Austria | 14 participants | 18 participants | 4 participants |
| Region of Enrollment Belgium | 9 participants | 11 participants | 2 participants |
| Region of Enrollment Bulgaria | 61 participants | 81 participants | 20 participants |
| Region of Enrollment Czech Republic | 43 participants | 58 participants | 15 participants |
| Region of Enrollment Denmark | 9 participants | 12 participants | 3 participants |
| Region of Enrollment France | 36 participants | 50 participants | 14 participants |
| Region of Enrollment Germany | 56 participants | 74 participants | 18 participants |
| Region of Enrollment Hungary | 39 participants | 54 participants | 15 participants |
| Region of Enrollment Italy | 12 participants | 17 participants | 5 participants |
| Region of Enrollment Netherlands | 17 participants | 23 participants | 6 participants |
| Region of Enrollment Poland | 64 participants | 86 participants | 22 participants |
| Region of Enrollment Romania | 37 participants | 50 participants | 13 participants |
| Region of Enrollment Russian Federation | 150 participants | 205 participants | 55 participants |
| Region of Enrollment Spain | 31 participants | 41 participants | 10 participants |
| Region of Enrollment United Kingdom | 46 participants | 59 participants | 13 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 232 / 627 | 76 / 216 |
| serious Total, serious adverse events | 50 / 627 | 22 / 216 |
Outcome results
Primary
Trough FEV1 (L) at 28 Weeks on Treatment
Trough FEV1 (mean of two highest FEV1 values assessed at 23 and 24 hours after inhalation) at 28 weeks
Time frame: Week 28
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 200 μg Once-daily | Trough FEV1 (L) at 28 Weeks on Treatment | 1.422 Liters | Standard Error 0.011 |
| Placebo | Trough FEV1 (L) at 28 Weeks on Treatment | 1.356 Liters | Standard Error 0.017 |
Primary
Trough Forced Expiratory Volume in the First Second (FEV1) (L) at 12 Weeks on Treatment
Trough FEV1 (mean of two highest FEV1 values assessed at 23 and 24 hours after inhalation) at 12 weeks
Time frame: Week 12
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 200 μg Once-daily | Trough Forced Expiratory Volume in the First Second (FEV1) (L) at 12 Weeks on Treatment | 1.428 Liters | Standard Error 0.01 |
| Placebo | Trough Forced Expiratory Volume in the First Second (FEV1) (L) at 12 Weeks on Treatment | 1.366 Liters | Standard Error 0.016 |
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 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) | 48.1 Percentage of Patients |
| Aclidinium 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) | 52.0 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) | 39.5 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) | 60.5 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: Week 52
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 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 |