Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, Emphysema, Airflow Obstruction, Chronic, Chronic Airflow Obstruction, Chronic Obstructive Airway Disease, Chronic Obstructive Lung Disease
Brief summary
The purpose of this Phase II study is to evaluate the pharmacokinetics, safety, and tolerability of aclidinium/formoterol fixed dose combination (FDC 400/12 μg via the Almirall Inhaler and formoterol 12 μg via the Foradil® Aerolizer®, both administered twice daily for five days to patients with moderate to severe COPD.
Interventions
DRUGAclidinium/formoterol 400/12μg
Aclidinium/formoterol 400/12μg fixed dose combination (FDC), one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Almirall inhaler
DRUGFormoterol
Formoterol 12 μg one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Foradil® Aerolizer®
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Current or former cigarette smokers with a cigarette smoking history of at least 10 pack-years * A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined by the Global Initiative for Chronic Obstructive Lung Disease guidelines and stable airway obstruction.
Exclusion criteria
* Patients who have been hospitalized for an acute COPD exacerbation within three months prior to Screening * Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Screening * Patients with any clinically significant respiratory conditions other than COPD * Clinical history that suggests that the patient has asthma as opposed to COPD * Chronic use of oxygen therapy ≥ 15 hours/day * Patients with clinically significant cardiovascular conditions * Patients with a history of hypersensitivity reaction to inhaled anticholinergics, beta-2 agonists, sympathomimetic amines, or inhaled medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose) | The standard deviation of the measure is expressed as the coefficient of variation (%) |
| Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose) | The standard deviation of the measure is expressed as the coefficient of variation (%) |
| Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose | The standard deviation of the measure is expressed as the coefficient of variation (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose | The standard deviation of the measure is expressed as the coefficient of variation (%) |
Countries
United States
Participant flow
Recruitment details
The study was conducted in a single center in the United States First patient visit was in January 2012 and last patient visit was in March 2012
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population All patients participating in the crossover study | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 7.5 |
| Gender Female | 10 Participants |
| Gender Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 2 / 24 |
Outcome results
Primary
Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State
The standard deviation of the measure is expressed as the coefficient of variation (%)
Time frame: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)
Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 12 μg | Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State | 87.14 pg*hr/mL | Standard Deviation 27.8 |
| Aclidinium/Formoterol 400/12 μg FDC | Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State | 85.15 pg*hr/mL | Standard Deviation 28.3 |
Primary
Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State
The standard deviation of the measure is expressed as the coefficient of variation (%)
Time frame: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)
Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 12 μg | Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State | 14.90 pg/mL | Standard Deviation 27.9 |
| Aclidinium/Formoterol 400/12 μg FDC | Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State | 16.72 pg/mL | Standard Deviation 31.6 |
Primary
Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose
The standard deviation of the measure is expressed as the coefficient of variation (%)
Time frame: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose
Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 12 μg | Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose | 8.23 pg/mL | Standard Deviation 39.9 |
| Aclidinium/Formoterol 400/12 μg FDC | Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose | 9.55 pg/mL | Standard Deviation 39 |
Secondary
Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose
The standard deviation of the measure is expressed as the coefficient of variation (%)
Time frame: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose
Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol 12 μg | Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose | 41.63 pg*hr/mL | Standard Deviation 32.2 |
| Aclidinium/Formoterol 400/12 μg FDC | Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose | 42.27 pg*hr/mL | Standard Deviation 31.3 |