Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Airflow Obstruction, Chronic, Chronic Airflow Obstruction, Chronic Obstructive Pulmonary Disease, Chronic Obstructive Airway Disease, Chronic Obstructive Lung Disease, COPD, COAD
Brief summary
This exploratory study will compare the efficacy of the fixed-dose combination (FDC) of aclidinium bromide and formoterol fumarate once daily in the morning and placebo once in the evening vs. the FDC once daily in the morning and formoterol fumarate once in the evening vs. formoterol fumarate twice daily. The study will assess pulmonary function and symptoms in patients with moderate to severe COPD.
Interventions
DRUGOnce-daily aclidinium/formoterol
Inhaled aclidinium bromide 200 µg/formoterol fumarate 12 µg fixed-dose combination once-daily in the morning
DRUGTwice-daily formoterol fumarate
Inhaled formoterol fumarate 12 µg twice-daily (BID)
DRUGPlacebo to formoterol fumarate
Inhaled placebo to formoterol fumarate once-daily in the evening
DRUGOnce-daily formoterol fumarate
Inhaled formoterol fumarate 12 μg once-daily in the evening
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Moderate to severe COPD * Smoking history of greater or equal to 10 pack-years * Diagnosis of stable moderate to severe COPD as defined by the GOLD Guidelines * Postbronchodilator FEV1 from 30% to 79% of predicted values, inclusive * Postbronchodilator FEV1/FVC ratio \< 0.70
Exclusion criteria
* History or presence of asthma, allergic rhinitis, or exercise-induced bronchospasm * Hospitalization for an 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 * Eosinophil count of at least 600 cells/mm3 * Long term oxygen therapy \> 15 hours a day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average Nocturnal Symptom Scores | Week 4 of treatment | Nocturnal Symptom Score Scale: 0 = None; 1 = Symptoms causing early awakening or awakening once during the night; 2 = Symptoms causing early awakening or awakening two or more times during the night; 3 = Symptoms causing awakening for most time during the night, 4 = Symptoms which were so severe that I could not sleep at all |
| Change From Baseline in Weekly Average Daily (24 Hour) Sputum Volume Scores | Week 4 of treatment | Sputum Volume Score Scale: 0 = None; 1 = The amount of one teaspoon; 2 = The amount of one tablespoon; 3 = More than one tablespoon |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) | Week 4 of treatment | The trough value for each pulmonary function parameter was defined as the mean of the two greatest readings assessed 23 hours and 24 hours following the administration of the morning dose of the previous day |
| Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | Week 4 of treatment | — |
| Change From Baseline in Normalized Area Under the Curve (0-3 hr) of Forced Expiratory Volume in One Second (FEV1) | Week 4 of treatment | FEV1 values obtained at 30, 60, 120, and 180 minutes after the morning study drug dose |
Countries
United States
Participant flow
Recruitment details
This study was conducted in 31 sites in the United States (US). All sites screened at least one patient and, of these 31 sites, three sites did not enroll any patients. The first patient was screened in March 2008 and the last patient visit was in February 2009.
Participants by arm
| Arm | Count |
|---|---|
| Once-daily Aclidinium/Formoterol Aclidinium bromide 200 μg and formoterol fumarate 12 μg fixed-dose combination once-daily in the morning plus placebo once every evening | 63 |
| Morning Aclidinium/Formoterol Plus Evening Formoterol Aclidinium bromide 200 μg and formoterol fumarate 12 μg fixed-dose combination once-daily in the morning plus formoterol fumarate alone 12 μg once every evening | 62 |
| Formoterol BID Formoterol fumarate 12 μg twice-daily (BID) | 31 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | Once-daily Aclidinium/Formoterol | Morning Aclidinium/Formoterol Plus Evening Formoterol | Formoterol BID | Total |
|---|---|---|---|---|
| Age, Continuous | 63.0 Years STANDARD_DEVIATION 7.2 | 63.9 Years STANDARD_DEVIATION 9 | 62.2 Years STANDARD_DEVIATION 10.1 | 63.2 Years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 28 Participants | 25 Participants | 15 Participants | 68 Participants |
| Sex: Female, Male Male | 35 Participants | 37 Participants | 16 Participants | 88 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 | 0 / 63 | 0 / 62 | 2 / 31 |
| serious Total, serious adverse events | 1 / 63 | 1 / 62 | 0 / 31 |
Outcome results
Primary
Change From Baseline in Weekly Average Daily (24 Hour) Sputum Volume Scores
Sputum Volume Score Scale: 0 = None; 1 = The amount of one teaspoon; 2 = The amount of one tablespoon; 3 = More than one tablespoon
Time frame: Week 4 of treatment
Population: Includes the number of patients in the randomized population with available analysis value at both baseline and a specific time point. Randomized population defined as all patients in the screened population who were randomized to a treatment group in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Once-daily Aclidinium/Formoterol | Change From Baseline in Weekly Average Daily (24 Hour) Sputum Volume Scores | -0.17 Units on a scale |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | Change From Baseline in Weekly Average Daily (24 Hour) Sputum Volume Scores | 0.13 Units on a scale |
| Formoterol BID | Change From Baseline in Weekly Average Daily (24 Hour) Sputum Volume Scores | -0.00 Units on a scale |
Primary
Change From Baseline in Weekly Average Nocturnal Symptom Scores
Nocturnal Symptom Score Scale: 0 = None; 1 = Symptoms causing early awakening or awakening once during the night; 2 = Symptoms causing early awakening or awakening two or more times during the night; 3 = Symptoms causing awakening for most time during the night, 4 = Symptoms which were so severe that I could not sleep at all
Time frame: Week 4 of treatment
Population: Includes the number of patients in the randomized population with available analysis value at both baseline and a specific time point. Randomized population defined as all patients in the screened population who were randomized to a treatment group in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Once-daily Aclidinium/Formoterol | Change From Baseline in Weekly Average Nocturnal Symptom Scores | -0.15 Units on a scale |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | Change From Baseline in Weekly Average Nocturnal Symptom Scores | -0.09 Units on a scale |
| Formoterol BID | Change From Baseline in Weekly Average Nocturnal Symptom Scores | -0.35 Units on a scale |
Other Pre-specified
Change From Baseline in Normalized Area Under the Curve (0-3 hr) of Forced Expiratory Volume in One Second (FEV1)
FEV1 values obtained at 30, 60, 120, and 180 minutes after the morning study drug dose
Time frame: Week 4 of treatment
Population: Includes the number of patients in the randomized population with available analysis value at both baseline and a specific time point. Randomized population defined as all patients in the screened population who were randomized to a treatment group in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Once-daily Aclidinium/Formoterol | Change From Baseline in Normalized Area Under the Curve (0-3 hr) of Forced Expiratory Volume in One Second (FEV1) | 0.257 Liters |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | Change From Baseline in Normalized Area Under the Curve (0-3 hr) of Forced Expiratory Volume in One Second (FEV1) | 0.226 Liters |
| Formoterol BID | Change From Baseline in Normalized Area Under the Curve (0-3 hr) of Forced Expiratory Volume in One Second (FEV1) | 0.200 Liters |
Other Pre-specified
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
Time frame: Week 4 of treatment
Population: Includes the number of patients in the randomized population with available analysis value at both baseline and a specific time point. Randomized population defined as all patients in the screened population who were randomized to a treatment group in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Once-daily Aclidinium/Formoterol | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.355 Liters |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.319 Liters |
| Formoterol BID | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.280 Liters |
Other Pre-specified
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1)
The trough value for each pulmonary function parameter was defined as the mean of the two greatest readings assessed 23 hours and 24 hours following the administration of the morning dose of the previous day
Time frame: Week 4 of treatment
Population: Includes the number of patients in the randomized population with available analysis value at both baseline and a specific time point. Randomized population defined as all patients in the screened population who were randomized to a treatment group in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Once-daily Aclidinium/Formoterol | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) | 0.097 Liters |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) | 0.084 Liters |
| Formoterol BID | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) | 0.118 Liters |