Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, antimuscarinic, COPD
Brief summary
The main purpose of this study is to assess the long term bronchodilator efficacy, safety and tolerability of inhaled aclidinium bromide at two dose levels compared to placebo in COPD patients and the benefits of the product in disease-related health status, COPD symptoms and COPD exacerbations.
Interventions
Aclidinium bromide 200 μg twice-daily via inhalation by the Eklira Genuair® inhaler: 1 puff in the morning and evening for 24 weeks
Aclidinium bromide 400 μg twice-daily via inhalation by the Eklira Genuair® inhaler: 1 puff in the morning and evening for 24 weeks
DRUGPlacebo
Placebo twice-daily by inhalation for 24 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
* Adult male and female patients aged ≥40 with stable moderate to severe COPD (GOLD guidelines). * Post-salbutamol (FEV1) \< 80% and ≥30% of predicted normal value and Post-salbutamol FEV1/FVC \< 70%. * Current or ex-smokers of ≥10 pack-years.
Exclusion criteria
* Patients with no history or current diagnosis of asthma. * No evidence of an exacerbation within 6 weeks prior to the screening visit. * No evidence of clinically significant respiratory and/or cardiovascular conditions or laboratory abnormalities. * No contraindication to use of anticholinergic drugs such as known symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | Baseline and Week 24 |
| Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 12 on Treatment | Baseline and Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peak Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | Baseline and Week 24 | — |
| Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | Week 24 | Number of patients achieving a clinically meaningful improvement (≥1-unit) in Transition Dyspnoea Index (TDI) focal score at Week 24 on Treatment |
| Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | Week 24 | Number of patients who achieved a clinically meaningful improvement (≥4-units) in Saint George Respiratory Questionnaire (SGRQ) total score at week 24 on treatment |
Countries
Czechia, France, Germany, Hungary, Italy, Peru, Poland, Russia, South Africa, Spain, Ukraine
Participant flow
Recruitment details
This study was conducted at 103 sites (100/103 randomised patients), 10 sites in the Czech Republic, 5 in France, 17 in Germany, 13 in Hungary, 3 in Italy, 1 in Peru, 21 in Poland, 10 in the Russian Federation, 5 in Spain, 13 in South Africa and 5 in the Ukraine. The first patient was screened in Oct 2009 and the last patient visit was in Nov 2010.
Pre-assignment details
Patients fulfilling inclusion/exclusion criteria at the time of the Screening Visit were entered into a run-in period of 14±3 days to assess patient's disease stability.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Bromide 200 μg Bid Aclidinium bromide 200 μg twice-daily via inhalation | 277 |
| Aclidinium Bromide 400 μg Bid Aclidinium bromide 400 μg twice-daily via inhalation | 269 |
| Placebo Placebo via inhalation | 273 |
| Total | 819 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 | 6 |
| Overall Study | COPD exacerbation | 3 | 4 | 5 |
| Overall Study | Lack of Efficacy | 2 | 0 | 8 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Other | 0 | 1 | 3 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 7 | 17 |
Baseline characteristics
| Characteristic | Aclidinium Bromide 200 μg Bid | Aclidinium Bromide 400 μg Bid | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 108 Participants | 108 Participants | 94 Participants | 310 Participants |
| Age, Categorical Between 18 and 65 years | 169 Participants | 161 Participants | 179 Participants | 509 Participants |
| Age, Continuous | 62.3 years STANDARD_DEVIATION 7.8 | 62.9 years STANDARD_DEVIATION 8.4 | 62.0 years STANDARD_DEVIATION 8 | 62.4 years STANDARD_DEVIATION 8 |
| Gender Female | 96 Participants | 87 Participants | 84 Participants | 267 Participants |
| Gender Male | 181 Participants | 182 Participants | 189 Participants | 552 Participants |
| Region of Enrollment Czech Republic | 22 participants | 20 participants | 19 participants | 61 participants |
| Region of Enrollment France | 8 participants | 8 participants | 8 participants | 24 participants |
| Region of Enrollment Germany | 55 participants | 57 participants | 56 participants | 168 participants |
| Region of Enrollment Hungary | 35 participants | 30 participants | 32 participants | 97 participants |
| Region of Enrollment Italy | 4 participants | 2 participants | 2 participants | 8 participants |
| Region of Enrollment Poland | 79 participants | 74 participants | 77 participants | 230 participants |
| Region of Enrollment Russian Federation | 14 participants | 16 participants | 15 participants | 45 participants |
| Region of Enrollment South Africa | 46 participants | 47 participants | 48 participants | 141 participants |
| Region of Enrollment Spain | 6 participants | 7 participants | 5 participants | 18 participants |
| Region of Enrollment Ukraine | 8 participants | 8 participants | 11 participants | 27 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 | 44 / 277 | 38 / 269 | 56 / 273 |
| serious Total, serious adverse events | 12 / 277 | 15 / 269 | 15 / 273 |
Outcome results
Primary
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 12 on Treatment
Time frame: Baseline and Week 12
Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 12 on Treatment | 0.030 Liters | Standard Error 0.014 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 12 on Treatment | 0.058 Liters | Standard Error 0.015 |
| Placebo | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 12 on Treatment | -0.047 Liters | Standard Error 0.015 |
Primary
Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment
Time frame: Baseline and Week 24
Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | 0.026 Liters | Standard Error 0.016 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | 0.055 Liters | Standard Error 0.016 |
| Placebo | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | -0.073 Liters | Standard Error 0.016 |
Secondary
Change From Baseline in Peak Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment
Time frame: Baseline and Week 24
Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 200 μg Bid | Change From Baseline in Peak Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | 0.206 Liters | Standard Error 0.017 |
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Peak Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | 0.231 Liters | Standard Error 0.017 |
| Placebo | Change From Baseline in Peak Forced Expiratory Volume in the First Second (FEV1) at Week 24 on Treatment | 0.022 Liters | Standard Error 0.017 |
Secondary
Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment
Number of patients achieving a clinically meaningful improvement (≥1-unit) in Transition Dyspnoea Index (TDI) focal score at Week 24 on Treatment
Time frame: Week 24
Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aclidinium Bromide 200 μg Bid | Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | Yes (% Patients with a 1-unit decrease) | 53.3 Percentage of participants |
| Aclidinium Bromide 200 μg Bid | Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | No (% Patients with a 1-unit decrease) | 46.7 Percentage of participants |
| Aclidinium Bromide 400 μg Bid | Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | Yes (% Patients with a 1-unit decrease) | 56.9 Percentage of participants |
| Aclidinium Bromide 400 μg Bid | Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | No (% Patients with a 1-unit decrease) | 43.1 Percentage of participants |
| Placebo | Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | No (% Patients with a 1-unit decrease) | 54.5 Percentage of participants |
| Placebo | Percentage of Patients Who Achieved at Least a 1-unit Decrease From Baseline in TDI Focal Score at Week 24 on Treatment | Yes (% Patients with a 1-unit decrease) | 45.5 Percentage of participants |
Secondary
Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment
Number of patients who achieved a clinically meaningful improvement (≥4-units) in Saint George Respiratory Questionnaire (SGRQ) total score at week 24 on treatment
Time frame: Week 24
Population: Intention-to-treat (ITT) population: all randomised patients who took at least one dose of Investigational Medicinal Product and who had a baseline and at least 1 post-baseline FEV1 assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aclidinium Bromide 200 μg Bid | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | Yes (% Patients with 4-unit decrease) | 56.0 Percentage of participants |
| Aclidinium Bromide 200 μg Bid | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | No (% Patients with 4-unit decrease) | 44.0 Percentage of participants |
| Aclidinium Bromide 400 μg Bid | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | Yes (% Patients with 4-unit decrease) | 57.3 Percentage of participants |
| Aclidinium Bromide 400 μg Bid | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | No (% Patients with 4-unit decrease) | 42.8 Percentage of participants |
| Placebo | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | Yes (% Patients with 4-unit decrease) | 41.0 Percentage of participants |
| Placebo | Percentage of Patients Who Achieved at Least a 4-unit Decrease From Baseline in the SGRQ Total Score at Week 24 on Treatment | No (% Patients with 4-unit decrease) | 59.0 Percentage of participants |