Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, antimuscarinic
Brief summary
The aim of the present study is to evaluate the 24h bronchodilatory efficacy of inhaled aclidinium bromide 400 µg administered twice a day versus placebo and tiotropium bromide, respectively, after 6 weeks of treatment.
Interventions
Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)
DRUGTiotropium
Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)
DRUGPlacebo
Dosage form: Dry powder Route of administration: Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h).
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 | Description |
|---|---|---|
| Change From Baseline in Normalised Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over the 24-h Period After 6 Weeks of Treatment | Week 6 | Change from baseline in normalised FEV1 area under the curve over the 24-h period immediately after morning Investigational Medicinal Product administration (AUC0-24h ) after 6 weeks on treatment. The normalised AUC were calculated by means of a trapezoidal method, dividing by the corresponding time interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Normalised FEV1 Area Under the Curve Over the 12-h Night-time Period After 6 Weeks of Treatment | Week 6 | Change from baseline in normalised FEV1 area under the curve over the 12-h night-time period (AUC12-24) after 6 weeks of treatment. The normalised AUC were calculated by means of a trapezoidal method, dividing by the corresponding time interval. |
Countries
Czechia, Germany, Hungary, Poland
Participant flow
Recruitment details
This study was conducted in 49 sites investigators in 4 countries (3 sites in the Czech Republic, 23 in Germany, 8 in Hungary and 15 in Poland). 8 sites (3 in Germany, 3 in Hungary and 2 in Poland) did not randomise any patients. The first patient was screened in Oct 2011 and the last patient visit was in Mar 2012.
Pre-assignment details
Patients fulfilling inclusion/exclusion criteria at the time of the screening visit were entered into a run-in period of 14-21 days to assess disease stability.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Bromide 400 µg BID Aclidinium bromide 400 µg administered twice per day
Dosage form: Dry powder. Route of administration: Oral inhalation by Genuair multidose dry powder inhaler.
Dose and regimen: 1 puff of 400 micrograms in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)
AND
1 capsule of placebo in the morning (09:00 ± 1h) via oral inhalation by HandiHaler single-dose dry powder inhaler. | 171 |
| Tiotropium 18 μg Once-daily Tiotropium 18 μg administered once daily
Dosage form: Dry powder hard gelatin capsule. Route of administration: Oral inhalation by HandiHaler single-dose dry powder inhaler.
Dose and regimen: 1 capsule (18 μg) in the morning (09:00 ± 1h)
AND
1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) via oral inhalation by Genuair multidose dry powder inhaler. | 158 |
| Placebo Placebo
Route of administration:
Oral inhalation by Genuair multidose dry powder inhaler. 1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h) AND Oral inhalation by HandiHaler single-dose dry powder inhaler. 1 capsule of placebo in the morning (09:00 ± 1h). | 85 |
| Total | 414 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Aclidinium Bromide 400 µg BID | Tiotropium 18 μg Once-daily | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 8.2 | 62.8 years STANDARD_DEVIATION 7.9 | 62.2 years STANDARD_DEVIATION 8.2 | 62.3 years STANDARD_DEVIATION 8.1 |
| Gender Female | 57 Participants | 42 Participants | 37 Participants | 136 Participants |
| Gender Male | 114 Participants | 116 Participants | 48 Participants | 278 Participants |
| Region of Enrollment Czech Republic | 5 participants | 3 participants | 3 participants | 11 participants |
| Region of Enrollment Germany | 84 participants | 81 participants | 40 participants | 205 participants |
| Region of Enrollment Hungary | 18 participants | 16 participants | 10 participants | 44 participants |
| Region of Enrollment Poland | 64 participants | 58 participants | 32 participants | 154 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 | 16 / 171 | 17 / 158 | 6 / 85 |
| serious Total, serious adverse events | 3 / 171 | 4 / 158 | 0 / 85 |
Outcome results
Primary
Change From Baseline in Normalised Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over the 24-h Period After 6 Weeks of Treatment
Change from baseline in normalised FEV1 area under the curve over the 24-h period immediately after morning Investigational Medicinal Product administration (AUC0-24h ) after 6 weeks on treatment. The normalised AUC were calculated by means of a trapezoidal method, dividing by the corresponding time interval.
Time frame: Week 6
Population: Intention to treat (ITT) population: patients who took at least 1 dose of Investigational Medicinal Product and had at least a baseline FEV1 assessment and at least one post-baseline FEV1 value
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 400 µg BID | Change From Baseline in Normalised Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over the 24-h Period After 6 Weeks of Treatment | 0.065 Liters | Standard Error 0.017 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over the 24-h Period After 6 Weeks of Treatment | 0.055 Liters | Standard Error 0.018 |
| Placebo | Change From Baseline in Normalised Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over the 24-h Period After 6 Weeks of Treatment | -0.085 Liters | Standard Error 0.023 |
Secondary
Change From Baseline in Normalised FEV1 Area Under the Curve Over the 12-h Night-time Period After 6 Weeks of Treatment
Change from baseline in normalised FEV1 area under the curve over the 12-h night-time period (AUC12-24) after 6 weeks of treatment. The normalised AUC were calculated by means of a trapezoidal method, dividing by the corresponding time interval.
Time frame: Week 6
Population: Intention to treat (ITT) population: patients who took at least 1 dose of Investigational Medicinal Product and had at least a baseline FEV1 assessment and at least one post-baseline FEV1 value
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 400 µg BID | Change From Baseline in Normalised FEV1 Area Under the Curve Over the 12-h Night-time Period After 6 Weeks of Treatment | 0.032 Liters | Standard Error 0.017 |
| Tiotropium 18 μg Once-daily | Change From Baseline in Normalised FEV1 Area Under the Curve Over the 12-h Night-time Period After 6 Weeks of Treatment | -0.006 Liters | Standard Error 0.018 |
| Placebo | Change From Baseline in Normalised FEV1 Area Under the Curve Over the 12-h Night-time Period After 6 Weeks of Treatment | -0.128 Liters | Standard Error 0.024 |