Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Antimuscarinic
Brief summary
The aim of the present study is to evaluate the effect of aclidinium bromide 400 μg twice a day (BID) administered twice a day versus placebo on exercise endurance and on hyperinflation and dyspnoea at rest and during exercise after 3 weeks of treatment.
Interventions
1 puff of 400 micro grams in the morning (09:00 ± 1h) and in the evening (21:00 ± 1h)
DRUGPlacebo
1 puff of placebo in the morning (09:00 ± 1h) and 1 puff in the evening (21:00 ± 1h)
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 (Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines). * Post-salbutamol Forced Expiratory Volume in one second(FEV1) \< 80% and ≥ 30% of predicted normal value and Post-salbutamol FEV1/Forced Vital Capacity (FVC) \< 70%. * Current or ex-smokers of ≥ 10 pack-years * Functional residual capacity (FRC) measured by body plethysmography at Screening Visit ≥ 120% of predicted value
Exclusion criteria
* History or current diagnosis of asthma * Signs of an exacerbation within 6 weeks ( or 3 months if results in hospitalisation) prior to the screening visit or during the run-in period. * Clinically significant respiratory and/or cardiovascular conditions or laboratory abnormalities. * Conditions where the use of anticholinergic drugs is contraindicated, such as known symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma. * Patients with an oxygen saturation \< 85% during cycle exercise on room air at Screening Visit, Run- in Visit and Visit 1. * Contra-indications of cardiopulmonary exercise testing. * Patient who in the investigator's opinion will need to start a pulmonary rehabilitation program during the study and/or patients who have just started/finished pulmonary rehabilitation at least 3 months prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Endurance Time (Seconds) | Week 3 | Change from baseline in endurance time during constant work rate cycle ergometry to symptom limitation at 75% of Maximum Work load (Wmax) after 3 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Inspiratory Capacity (IC) (Litres) | Week 3 | Change from baseline in trough IC after 3 weeks of treatment |
| Change From Baseline in Intensity of Dyspnoea | Week 3 | Change from baseline in intensity of dyspnoea based on the Borg CR10 Scale® (ranging from '0'=nothing at all to '10'=extremely strong/maximal dyspnoea, the highest possible numerical value) at isotime during constant work rate cycle ergometry after 3 weeks of treatment. |
Countries
Germany, Spain, United Kingdom
Participant flow
Recruitment details
This study was conducted at 16 enrolling sites. A total of 14 sites randomised patients: 10 sites in Germany, 3 sites in Spain and one site in the United Kingdom. The first patient was screened in November 2011 and the last patient visit was in June 2012.
Pre-assignment details
Eligible patients entered a 14-21 day run-in period to assess disease stability. During this period, one site visit was performed to familiarise patients with study testing procedures (body plethysmography, spirometry and a constant work rate cycle exercise test).
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Safety Population All patients randomized into the crossover study were included in the safety population | 112 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 4 | 1 |
| Treatment Period 2 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study Safety Population |
|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 8.1 |
| Gender Female | 36 Participants |
| Gender Male | 76 Participants |
| Region of Enrollment Germany | 89 participants |
| Region of Enrollment Spain | 20 participants |
| Region of Enrollment United Kingdom | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 111 | 4 / 108 |
| serious Total, serious adverse events | 0 / 111 | 2 / 108 |
Outcome results
Primary
Change From Baseline in Endurance Time (Seconds)
Change from baseline in endurance time during constant work rate cycle ergometry to symptom limitation at 75% of Maximum Work load (Wmax) after 3 weeks of treatment.
Time frame: Week 3
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of investigational medicinal product, and had at least a baseline and one post-dose corresponding assessment value of the primary efficacy variable in one of the 2 treatment periods. 2 patients from the safety population were excluded from the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Endurance Time (Seconds) | 68.3 Seconds | Standard Error 18.8 |
| Placebo | Change From Baseline in Endurance Time (Seconds) | 9.8 Seconds | Standard Error 19 |
Secondary
Change From Baseline in Intensity of Dyspnoea
Change from baseline in intensity of dyspnoea based on the Borg CR10 Scale® (ranging from '0'=nothing at all to '10'=extremely strong/maximal dyspnoea, the highest possible numerical value) at isotime during constant work rate cycle ergometry after 3 weeks of treatment.
Time frame: Week 3
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of investigational medicinal product, and had at least a baseline and one post-dose corresponding assessment value of the primary efficacy variable in one of the 2 treatment periods. 2 patients from the safety population were excluded from the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Intensity of Dyspnoea | -0.48 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Intensity of Dyspnoea | 0.15 Units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline in Trough Inspiratory Capacity (IC) (Litres)
Change from baseline in trough IC after 3 weeks of treatment
Time frame: Week 3
Population: Intention-to-Treat (ITT) population: all randomised patients who took at least one dose of investigational medicinal product, and had at least a baseline and one post-dose corresponding assessment value of the primary efficacy variable in one of the 2 treatment periods. 2 patients from the safety population were excluded from the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium Bromide 400 μg Bid | Change From Baseline in Trough Inspiratory Capacity (IC) (Litres) | 0.098 Litres | Standard Error 0.024 |
| Placebo | Change From Baseline in Trough Inspiratory Capacity (IC) (Litres) | 0.020 Litres | Standard Error 0.025 |