Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
The purpose of this study is to determine if SYMBICORT® delivered via a pressurized metered-dose inhaler, referred to as a pMDI, is effective in preventing COPD exacerbations.
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A current clinical diagnosis of COPD with COPD symptoms for more than 2 years * Current smoker or smoking history of 10 or more pack years (1 pack year = 20 cigarettes smoked per day for one year) * A history of at least 1 COPD exacerbations requiring a course of steroids and/or antibiotics within 1-12 months before the first visit
Exclusion criteria
* A history of asthma at or after 18 years of age * A history of allergic rhinitis at or after 18 years of age * Subjects taking oral steroids * Any significant disease or disorder that may jeopardize a subject's safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient-treatment Year | 12 months | Number of COPD-related exacerbations per patient-treatment year. COPD-related exacerbation was defined as worsening COPD that required a course of oral steriods for treatment and/or hospitalization. |
| Rate of Exacerbations Per Subject-year | 12 months | Rate of exacerbations per subject-year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evening PEF | 12 months | Change in evening PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline evening PEF value. |
| Dyspnea Symptom Scores | 12 months | Change from baseline of Dyspnea symptoms evaluated using the breathlessness diary, a 5-point Likert-type scale, ranging from 0 to 4 with higher scores indicating a more severe manifestation of the Dyspnea symptom. Change from baseline was calculated by averaging treatment period Dyspnea scores and subtracting the baseline Dyspnea scores. |
| Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 12 months | Change in pre-dose FEV1 from baseline to the average of the randomized treatment period, as calculated by averaging treatment period FEV1 values and subtracting the pre-dose value. |
| St. George's Respiratory Questionnaire (SGRQ) Score | 12 months | Change from baseline in the SGRQ overall score, as calculated by averaging treatment period SGRQ scores and subtracting the baseline SGRQ scores. The SGRQ contains 3 domains: Symptoms (distress due to respiratory symptoms, 8 questions), Activity (disturbance of physical activity, 16 questions), and Impacts (overall impact on daily life and well-being, 26 questions). Lower scores are associated with less severe symptoms. |
| Use of Rescue Medication | 12 months | Change from baseline in the use of beta-2 agonists, as calculated by averaging treatment period inhalations per day and subtracting the baseline number of inhalations per day. |
| Morning Peak Expiratory Flow (PEF) | 12 months | Change in morning PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline morning PEF value. |
Countries
Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, United States, Venezuela
Participant flow
Recruitment details
First patient randomized on 02 January 2007. The last patient completed study on 27 August 2009. The study randomized patients in the United States and Mexico (93 investigational sites), South America (48 investigational sites), and South Africa (20 investigational sites).
Pre-assignment details
The study consisted of an initial screening visit (Visit 1) and 2-week run-in enrollment visits (Visits 2 and 3) prior to being randomized to 1 of 3 treatment groups
Participants by arm
| Arm | Count |
|---|---|
| SYM 160/4.5 X 2 BID SYMBICORT pMDI (budesonide/formoterol) 160/4.5 μg (delivered dose) per actuation, 2 actuations administered twice daily (BID) | 407 |
| SYM 80/4.5 X 2 BID SYMBICORT pMDI (budesonide/formoterol) 80/4.5 μg (delivered dose) per actuation, 2 actuations administered BID | 408 |
| FOR 4.5 X 2 BID Formoterol Turbuhaler 4.5 μg x 2 inhalations BID | 403 |
| Total | 1,218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 39 | 40 | 50 |
| Overall Study | Incorrect medication kit dispensed | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 8 | 10 | 6 |
| Overall Study | Moving out of state | 2 | 0 | 1 |
| Overall Study | Physician Decision | 10 | 5 | 6 |
| Overall Study | Protocol Violation | 4 | 7 | 8 |
| Overall Study | Randomized in error | 9 | 6 | 7 |
| Overall Study | Spirometry mouthpiece issues | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 45 | 49 | 52 |
Baseline characteristics
| Characteristic | SYM 160/4.5 X 2 BID | SYM 80/4.5 X 2 BID | FOR 4.5 X 2 BID | Total |
|---|---|---|---|---|
| Age Continuous | 63.8 Years STANDARD_DEVIATION 9.4 | 62.8 Years STANDARD_DEVIATION 9.22 | 62.5 Years STANDARD_DEVIATION 9.36 | 63.0 Years STANDARD_DEVIATION 9.34 |
| Sex: Female, Male Female | 145 Participants | 144 Participants | 174 Participants | 463 Participants |
| Sex: Female, Male Male | 262 Participants | 264 Participants | 229 Participants | 755 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 | 193 / 407 | 177 / 408 | 176 / 403 |
| serious Total, serious adverse events | 79 / 407 | 61 / 408 | 73 / 403 |
Outcome results
Primary
Rate of Exacerbations Per Subject-year
Rate of exacerbations per subject-year
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYM 160/4.5 X 2 BID | Rate of Exacerbations Per Subject-year | 0.639 Rate |
| SYM 80/4.5 X 2 BID | Rate of Exacerbations Per Subject-year | 0.745 Rate |
| FOR 4.5 X 2 BID | Rate of Exacerbations Per Subject-year | 1.029 Rate |
Primary
Total Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient-treatment Year
Number of COPD-related exacerbations per patient-treatment year. COPD-related exacerbation was defined as worsening COPD that required a course of oral steriods for treatment and/or hospitalization.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYM 160/4.5 X 2 BID | Total Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient-treatment Year | 0.75 Exacerbations |
| SYM 80/4.5 X 2 BID | Total Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient-treatment Year | 0.84 Exacerbations |
| FOR 4.5 X 2 BID | Total Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient-treatment Year | 1.14 Exacerbations |
Secondary
Dyspnea Symptom Scores
Change from baseline of Dyspnea symptoms evaluated using the breathlessness diary, a 5-point Likert-type scale, ranging from 0 to 4 with higher scores indicating a more severe manifestation of the Dyspnea symptom. Change from baseline was calculated by averaging treatment period Dyspnea scores and subtracting the baseline Dyspnea scores.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYM 160/4.5 X 2 BID | Dyspnea Symptom Scores | -0.30 Scores on a scale | Standard Deviation 0.65 |
| SYM 80/4.5 X 2 BID | Dyspnea Symptom Scores | -0.29 Scores on a scale | Standard Deviation 0.7 |
| FOR 4.5 X 2 BID | Dyspnea Symptom Scores | -0.24 Scores on a scale | Standard Deviation 0.67 |
Secondary
Evening PEF
Change in evening PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline evening PEF value.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYM 160/4.5 X 2 BID | Evening PEF | 17.62 L/min | Standard Deviation 37.86 |
| SYM 80/4.5 X 2 BID | Evening PEF | 17.77 L/min | Standard Deviation 37.67 |
| FOR 4.5 X 2 BID | Evening PEF | 14.08 L/min | Standard Deviation 41.13 |
Secondary
Morning Peak Expiratory Flow (PEF)
Change in morning PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline morning PEF value.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYM 160/4.5 X 2 BID | Morning Peak Expiratory Flow (PEF) | 19.82 L/min | Standard Deviation 37.96 |
| SYM 80/4.5 X 2 BID | Morning Peak Expiratory Flow (PEF) | 19.61 L/min | Standard Deviation 38.83 |
| FOR 4.5 X 2 BID | Morning Peak Expiratory Flow (PEF) | 15.81 L/min | Standard Deviation 41.43 |
Secondary
Pre-dose Forced Expiratory Volume in 1 Second (FEV1)
Change in pre-dose FEV1 from baseline to the average of the randomized treatment period, as calculated by averaging treatment period FEV1 values and subtracting the pre-dose value.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYM 160/4.5 X 2 BID | Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.07 Liters (L) | Standard Deviation 0.18 |
| SYM 80/4.5 X 2 BID | Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.07 Liters (L) | Standard Deviation 0.17 |
| FOR 4.5 X 2 BID | Pre-dose Forced Expiratory Volume in 1 Second (FEV1) | 0.04 Liters (L) | Standard Deviation 0.17 |
Secondary
St. George's Respiratory Questionnaire (SGRQ) Score
Change from baseline in the SGRQ overall score, as calculated by averaging treatment period SGRQ scores and subtracting the baseline SGRQ scores. The SGRQ contains 3 domains: Symptoms (distress due to respiratory symptoms, 8 questions), Activity (disturbance of physical activity, 16 questions), and Impacts (overall impact on daily life and well-being, 26 questions). Lower scores are associated with less severe symptoms.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYM 160/4.5 X 2 BID | St. George's Respiratory Questionnaire (SGRQ) Score | -6.23 Scores on a scale | Standard Deviation 14.72 |
| SYM 80/4.5 X 2 BID | St. George's Respiratory Questionnaire (SGRQ) Score | -5.00 Scores on a scale | Standard Deviation 16.1 |
| FOR 4.5 X 2 BID | St. George's Respiratory Questionnaire (SGRQ) Score | -5.71 Scores on a scale | Standard Deviation 15.31 |
Secondary
Use of Rescue Medication
Change from baseline in the use of beta-2 agonists, as calculated by averaging treatment period inhalations per day and subtracting the baseline number of inhalations per day.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYM 160/4.5 X 2 BID | Use of Rescue Medication | -1.21 Number of inhalations | Standard Deviation 3.57 |
| SYM 80/4.5 X 2 BID | Use of Rescue Medication | -1.03 Number of inhalations | Standard Deviation 3.74 |
| FOR 4.5 X 2 BID | Use of Rescue Medication | -0.28 Number of inhalations | Standard Deviation 3.6 |