Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Onset of effect, COPD, Oxis Turbuhaler
Brief summary
* Primary objective is to evaluate time to onset of effect of formoterol, 9 μg single dose,compared with salmeterol, 50 μg single dose, in patients with moderate COPD.Forced Expiratory Volume in 1 second (FEV1) measured by spirometry 5 minutes postdose. * Secondary efficacy variables: Average FEV1 during the first 15 minutes (area under the FEV1 curve from 0 to 15 minutes), Average FEV1 during 120 minutes (area under the FEV1 curve from 0 to 120 minutes)
Interventions
DRUGPlacebo
Placebo Diskus and Placebo Turbuhaler
DRUGFormoterol
Formoterol Turbuhaler 9 μg and Placebo Diskus
DRUGSalmeterol
Salmeterol Diskus 50 μg and Placebo Turbuhaler
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
* A clinical diagnosis of COPD according to GOLD guidelines, and current COPD symptoms * A current or previous smoking history equivalent to 10 or more packs per year (1 pack year = 20 cigarettes smoked per day for one year). * Documented use of a short-acting inhaled bronchodilator (β2-agonist or anticholinergics) as reliever medication.
Exclusion criteria
* A history and/or current diagnosis of asthma. * Patients who have experienced COPD exacerbation requiring hospitalisation and/or a course of antibiotics and/or a course of systemic steroid within 30 days (from end of exacerbation treatment) prior to Visit 1 and/or during the run-in period. * A history and/or current diagnosis of atopic diseases such as allergic rhinitis or eczema before the age of 40.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1(Forced Expiratory Volume in 1 Second) Measured by Spirometry 5 Minutes Post Dose | Pre-dose and 5 minutes post-dose | FEV1(Forced Expiratory Volume in 1 second) measured by spirometry 5 minutes post dose, percentage change versus pre dose FEV1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average FEV1 During the First 15 Minutes Post Dose | Pre dose and 15 minutes post dose | Average FEV1 during the first 15 minutes post dose, change versus pre dose FEV1 |
| Adverse Events | At baseline and at each day of treatment | Number of participants with at least 1 AE. |
| Average FEV1 During 120 Minutes Post Dose | Pre dose and 120 minutes post dose | Average FEV1 during 120 minutes post dose, change versus pre dose FEV1 |
| Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | Pre dose, 5, 10, 15, 20, 30, 40, 50, 60 and 120 minutes post dose | Percentage of patients who has achieved at least 12 % increase in FEV1 at each time point between 5 to 120 minutes post dose, change versus pre dose FEV1 |
Countries
Italy, Spain, Sweden
Participant flow
Recruitment details
Patients recruited at 14 clinics in 3 countries: Sweden (4 clinics); Italy (6 clinics); Spain (6 clinics)between January and May 2010
Pre-assignment details
141 patients enrolled; 32 excluded: 28 due to eligibility criteria not fulfilled and 4 for subject decision
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all 3 arms : Formoterol, Salmeterol and Placebo. | 109 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Wash-Out Period 2 of 2 - 7 Days | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 66.5 years |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 81 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 / 108 | 0 / 109 | 0 / 109 |
| serious Total, serious adverse events | 0 / 108 | 0 / 109 | 0 / 109 |
Outcome results
Primary
FEV1(Forced Expiratory Volume in 1 Second) Measured by Spirometry 5 Minutes Post Dose
FEV1(Forced Expiratory Volume in 1 second) measured by spirometry 5 minutes post dose, percentage change versus pre dose FEV1
Time frame: Pre-dose and 5 minutes post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol | FEV1(Forced Expiratory Volume in 1 Second) Measured by Spirometry 5 Minutes Post Dose | 1.072 percentage change |
| Salmeterol | FEV1(Forced Expiratory Volume in 1 Second) Measured by Spirometry 5 Minutes Post Dose | 1.041 percentage change |
| Placebo | FEV1(Forced Expiratory Volume in 1 Second) Measured by Spirometry 5 Minutes Post Dose | 1.007 percentage change |
Secondary
Adverse Events
Number of participants with at least 1 AE.
Time frame: At baseline and at each day of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Formoterol | Adverse Events | 6 Participants |
| Salmeterol | Adverse Events | 6 Participants |
| Placebo | Adverse Events | 2 Participants |
Secondary
Average FEV1 During 120 Minutes Post Dose
Average FEV1 during 120 minutes post dose, change versus pre dose FEV1
Time frame: Pre dose and 120 minutes post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol | Average FEV1 During 120 Minutes Post Dose | 1.096 percentage change |
| Salmeterol | Average FEV1 During 120 Minutes Post Dose | 1.082 percentage change |
| Placebo | Average FEV1 During 120 Minutes Post Dose | 1.014 percentage change |
Secondary
Average FEV1 During the First 15 Minutes Post Dose
Average FEV1 during the first 15 minutes post dose, change versus pre dose FEV1
Time frame: Pre dose and 15 minutes post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Formoterol | Average FEV1 During the First 15 Minutes Post Dose | 1.064 percentage change |
| Salmeterol | Average FEV1 During the First 15 Minutes Post Dose | 1.041 percentage change |
| Placebo | Average FEV1 During the First 15 Minutes Post Dose | 1.012 percentage change |
Secondary
Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1
Percentage of patients who has achieved at least 12 % increase in FEV1 at each time point between 5 to 120 minutes post dose, change versus pre dose FEV1
Time frame: Pre dose, 5, 10, 15, 20, 30, 40, 50, 60 and 120 minutes post dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 50 min | 53.7 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 10 min | 38.0 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 15 min | 39.8 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 40 min | 49.1 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 120 min | 55.6 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 20 min | 44.4 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 60 min | 54.6 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 30 min | 45.4 Percentage of Participants |
| Formoterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 5 min | 23.1 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 40 min | 36.7 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 5 min | 9.2 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 60 min | 43.1 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 120 min | 48.6 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 50 min | 40.4 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 15 min | 23.9 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 10 min | 17.6 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 20 min | 27.5 Percentage of Participants |
| Salmeterol | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 30 min | 32.1 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 120 min | 20.2 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 5 min | 6.4 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 30 min | 13.8 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 10 min | 7.3 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 15 min | 9.2 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 20 min | 10.1 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 40 min | 15.6 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 50 min | 16.5 Percentage of Participants |
| Placebo | Percentage of Patients Who Has Achieved at Least 12 % Increase in FEV1 | 60 min | 18.3 Percentage of Participants |
p-value: 0.00295% CI: [1.31, 3.35]Regression, Cox
p-value: 0.00195% CI: [3.55, 12.02]Regression, Cox
p-value: 0.00195% CI: [1.77, 5.52]Regression, Cox