Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Bronchitis, Chronic; Emphysema
Brief summary
This study evaluated the effect of inhaled aclidinium bromide on exercise endurance and in reducing resting and dynamic lung hyperinflation in patients with moderate to severe COPD. It was 9 weeks in duration, consisting of; a 2-week run-in period, 6 weeks of double-blind treatment, and a 1-week follow-up phone call. All patients meeting the eligibility criteria were randomized to one of two treatment groups: aclidinium bromide or placebo.
Interventions
Aclidinium Bromide, 200μg. Once daily oral inhalation.
DRUGPlacebo
Dose matched placebo, once daily oral inhalation.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A diagnosis of stable moderate to severe COPD (GOLD 2006); post-levalbuterol FEV1 \>=30% and \< 80% predicted and FEV1/FVC\<70% predicted * Current or former cigarette smoker * Functional Residual Capacity (FRC) measured by body plethysmography \>= 120% of predicted value * Baseline Dyspnea Index (BDI) focal score ≤ 7 at Visit 4
Exclusion criteria
* History of presence of asthma, allergic rhinitis, or atopy * Hospitalization for acute COPD exacerbation in the 3 months prior to study entry * Respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks prior to study entry * Clinically significant respiratory conditions other than COPD * Chronic use of oxygen therapy \>= 15 hours a day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Exercise Endurance Time (ET) | From baseline Week 0 (Visit 4) to Week 6 (Visit 6) | Exercise endurance time is defined as the time from the increase in work rate at 75% Wmax (watts) to the point of symptom limitation. The Wmax is defined as the highest work rate the patients were able to maintain for at least 30 seconds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) | Change from baseline (Visit 4) at Week 6 (Visit 6) | Change in trough Forced Expiratory Volume in 1 second. FEV1 was assessed at the end of the daily dosing interval (Trough). |
| Trough Inspiratory Capacity (IC) | Change from baseline Week 0 (Visit 4) to Week 6 (Visit 6) | Change in trough Inspiratory Capacity. Inspiratory Capacity was measured as part of the spirometry procedures performed at each visit. IC was assessed at the end of the daily dosing interval (Trough). |
| Functional Residual Capacity (FRC) | Change from baseline Week 0 (Visit 4) to Week 6 (Visit 6) | Change in trough Functional Residual Capacity. FRC was assessed at the end of the daily dosing interval (Trough). |
| Inspiratory Capacity (IC)/Total Lung Capacity (TLC) Ratio | Change from baseline Week 0 (Visit 4) to Week 6 (Visit 6) | Ratio of trough Inspiratory Capacity verses Total Lung Capacity. |
Countries
Canada, United States
Participant flow
Recruitment details
Patient recruitment occurred from July to October of 2007 at 52 study sites (42 sites in the United States and 10 additional sites in Canada)
Pre-assignment details
All demographic and baseline characteristics were analyzed descriptively just for the Safety population.
Participants by arm
| Arm | Count |
|---|---|
| Aclidinium Aclidinium bromide, 200 micrograms, oral inhalation once per day. | 86 |
| Placebo Dose-matched placebo, oral inhalation, once per day. | 95 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 8 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Other Reason | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Aclidinium | Total |
|---|---|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 7.8 | 64.0 years STANDARD_DEVIATION 9.5 | 64.8 years STANDARD_DEVIATION 8.6 |
| Gender Female | 42 Participants | 34 Participants | 76 Participants |
| Gender Male | 53 Participants | 52 Participants | 105 Participants |
| Region of Enrollment Canada | 20 participants | 22 participants | 42 participants |
| Region of Enrollment United States | 75 participants | 64 participants | 139 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 86 | 18 / 95 |
| serious Total, serious adverse events | 2 / 86 | 3 / 95 |
Outcome results
Primary
Change From Baseline in Exercise Endurance Time (ET)
Exercise endurance time is defined as the time from the increase in work rate at 75% Wmax (watts) to the point of symptom limitation. The Wmax is defined as the highest work rate the patients were able to maintain for at least 30 seconds.
Time frame: From baseline Week 0 (Visit 4) to Week 6 (Visit 6)
Population: Missing data for patients who withdrew due to COPD exacerbations was imputed using the Worst Observation Carried Forward (WOCF) of all Endurance time (ET), while ETs that were missing for other reasons were imputed using the Last Observation Carried Forward (LOCF) method based on the last visit available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium | Change From Baseline in Exercise Endurance Time (ET) | 129.45 Seconds | Standard Error 31.19 |
| Placebo | Change From Baseline in Exercise Endurance Time (ET) | 13.01 Seconds | Standard Error 30.97 |
p-value: 0.004295% CI: [37.28, 195.61]ANCOVA
Secondary
Functional Residual Capacity (FRC)
Change in trough Functional Residual Capacity. FRC was assessed at the end of the daily dosing interval (Trough).
Time frame: Change from baseline Week 0 (Visit 4) to Week 6 (Visit 6)
Population: The Intent-to-Treat (ITT) population consisted of all patients in the Safety Population who had at least a baseline and one post-baseline assessment of the primary efficacy parameter. Missing values due to a premature discontinuation or patients who missed specific trial visits were imputed by Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium | Functional Residual Capacity (FRC) | -0.138 L | Standard Error 0.061 |
| Placebo | Functional Residual Capacity (FRC) | -0.076 L | Standard Error 0.064 |
Secondary
Inspiratory Capacity (IC)/Total Lung Capacity (TLC) Ratio
Ratio of trough Inspiratory Capacity verses Total Lung Capacity.
Time frame: Change from baseline Week 0 (Visit 4) to Week 6 (Visit 6)
Population: The Intent-to-Treat (ITT) population consisted of all patients in the Safety Population who had at least a baseline and one post-baseline assessment of the primary efficacy parameter. Missing values due to a premature discontinuation or patients who missed specific trial visits were imputed by Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium | Inspiratory Capacity (IC)/Total Lung Capacity (TLC) Ratio | 0.014 ratio | Standard Error 0.006 |
| Placebo | Inspiratory Capacity (IC)/Total Lung Capacity (TLC) Ratio | -0.003 ratio | Standard Error 0.006 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1)
Change in trough Forced Expiratory Volume in 1 second. FEV1 was assessed at the end of the daily dosing interval (Trough).
Time frame: Change from baseline (Visit 4) at Week 6 (Visit 6)
Population: The Intent-to-Treat (ITT) population consisted of all patients in the Safety Population who had at least a baseline and one post-baseline assessment of the primary efficacy parameter. Missing values due to a premature discontinuation or patients who missed specific trial visits were imputed by Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium | Trough Forced Expiratory Volume in 1 Second (FEV1) | 0.090 L | Standard Error 0.018 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) | -0.010 L | Standard Error 0.018 |
Secondary
Trough Inspiratory Capacity (IC)
Change in trough Inspiratory Capacity. Inspiratory Capacity was measured as part of the spirometry procedures performed at each visit. IC was assessed at the end of the daily dosing interval (Trough).
Time frame: Change from baseline Week 0 (Visit 4) to Week 6 (Visit 6)
Population: The Intent-to-Treat (ITT) population consisted of all patients in the Safety Population who had at least a baseline and one post-baseline assessment of the primary efficacy parameter. Missing values due to a premature discontinuation or patients who missed specific trial visits were imputed by Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aclidinium | Trough Inspiratory Capacity (IC) | 0.083 L | Standard Error 0.032 |
| Placebo | Trough Inspiratory Capacity (IC) | -0.019 L | Standard Error 0.032 |