Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Antimuscarinic
Brief summary
The main purpose of this study is to evaluate the efficacy, safety and tolerability of multiple doses of inhaled aclidinium bromide in moderate to severe COPD patients.
Interventions
DRUGTiotropium 18 μg once-daily
Tiotropium 18 μg once-daily via inhalation by Handihaler® dry powder inhaler: 1 puff in the morning for 15 days.
DRUGPlacebo
Inhaled placebo: 1 puff in the morning (placebo to tiotropium) or in the morning and evening (placebo to aclidnium) for 15 days.
Aclidinium bromide 400 μg twice-daily via inhalation by the Eklira Genuair® inhaler: 1 puff in the morning and evening for 15 days.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment. | Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | Day 15 |
| Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC0-12) in Liters at Day 1 on Treatment | Day 1 |
| Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | Day 1 |
| Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | Day 1 |
| Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment | Day 15 |
| Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24hr at Day 15 on Treatment | Day 15 |
| Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | Day 15 |
| Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 1 on Treatment | Day 1 |
| Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | Day 1 |
| Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | Day 1 |
| Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 15 on Treatment | Day 15 |
Countries
Germany
Participant flow
Recruitment details
This study was conducted at 2 sites in Germany. The first patient was screened in Mar 2009 and the last patient visit was in Jul 2009.
Pre-assignment details
Eligible patients had at least a 5-day run-in period (and a maximum of 9 days) to assess patient's clinical stability.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population All patients randomized into the crossover study | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 2 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 3 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 7.9 |
| Gender Female | 11 Participants |
| Gender Male | 19 Participants |
| Region of Enrollment Germany | 30 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 | 2 / 29 | 0 / 28 | 3 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 28 | 1 / 30 |
Outcome results
Primary
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment.
Time frame: Day 15
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment. | 0.236 Liters | Standard Error 0.069 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment. | 0.260 Liters | Standard Error 0.07 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment. | 0.015 Liters | Standard Error 0.07 |
Secondary
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC0-12) in Liters at Day 1 on Treatment
Time frame: Day 1
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC0-12) in Liters at Day 1 on Treatment | 0.230 Liters | Standard Error 0.04 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC0-12) in Liters at Day 1 on Treatment | 0.178 Liters | Standard Error 0.04 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC0-12) in Liters at Day 1 on Treatment | 0.016 Liters | Standard Error 0.04 |
Secondary
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment
Time frame: Day 15
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | 0.226 Liters | Standard Error 0.063 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | 0.178 Liters | Standard Error 0.063 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | -0.006 Liters | Standard Error 0.063 |
Secondary
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment
Time frame: Day 1
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | 0.211 Liters | Standard Error 0.044 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | 0.138 Liters | Standard Error 0.044 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | -0.024 Liters | Standard Error 0.044 |
Secondary
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24hr at Day 15 on Treatment
Time frame: Day 15
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24hr at Day 15 on Treatment | 0.174 Liters | Standard Error 0.07 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24hr at Day 15 on Treatment | 0.096 Liters | Standard Error 0.07 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24hr at Day 15 on Treatment | -0.032 Liters | Standard Error 0.071 |
Secondary
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment
Time frame: Day 1
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | 0.202 Liters | Standard Error 0.051 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | 0.101 Liters | Standard Error 0.051 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | -0.060 Liters | Standard Error 0.05 |
Secondary
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment
Time frame: Day 15
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment | 0.297 Liters | Standard Error 0.083 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment | 0.345 Liters | Standard Error 0.083 |
| Placebo | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 15 on Treatment | 0.009 Liters | Standard Error 0.084 |
Secondary
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 1 on Treatment
Time frame: Day 1
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 1 on Treatment | 0.331 Liters | Standard Error 0.064 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 1 on Treatment | 0.289 Liters | Standard Error 0.064 |
| Placebo | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-12 hr at Day 1 on Treatment | 0.005 Liters | Standard Error 0.063 |
Secondary
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment
Time frame: Day 15
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | 0.281 Liters | Standard Error 0.078 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | 0.219 Liters | Standard Error 0.078 |
| Placebo | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 15 on Treatment | -0.039 Liters | Standard Error 0.078 |
Secondary
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment
Time frame: Day 1
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | 0.310 Liters | Standard Error 0.067 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | 0.215 Liters | Standard Error 0.067 |
| Placebo | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 0-24 hr at Day 1 on Treatment | -0.051 Liters | Standard Error 0.066 |
Secondary
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 15 on Treatment
Time frame: Day 15
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 15 on Treatment | 0.224 Liters | Standard Error 0.074 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 15 on Treatment | 0.087 Liters | Standard Error 0.074 |
| Placebo | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 15 on Treatment | -0.095 Liters | Standard Error 0.075 |
Secondary
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment
Time frame: Day 1
Population: Intention-to-treat (ITT) population; patients were included who took at least one dose of Investigational Medicinal Product and had at least a baseline and one post-dose value of FEV1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidininum Bromide 400 μg Bid | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | 0.293 Liters | Standard Error 0.072 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | 0.150 Liters | Standard Error 0.073 |
| Placebo | Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve (AUC) 12-24 hr at Day 1 on Treatment | -0.127 Liters | Standard Error 0.072 |