Asthma
Conditions
Keywords
Asthma
Brief summary
The primary objective of this study is to evaluate efficacy of AZD1981 in uncontrolled asthmatic patients on maintenance inhaled glucocorticosteroids.
Interventions
DRUGAZD1981
Oral tablet, 50 mg twice daily
DRUGPlacebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Six months history of asthma * Daily use of inhaled glucocorticosteroids * FEV1 40-85% of predicted normal * Reversibility; increase in FEV1 more than 12% and 200 mL post-bronchodilator
Exclusion criteria
* Other clinically relevant disease or disorders * History of smoking of more than 10 pack years * Respiratory infection within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morning Peak Expiratory Flow (mPEF) | Week 4 | Mean mPEF during the treatment period (mean of the last 2 weeks of the treatment period) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evening Forced Expiratory Volume in 1 Second (eFEV1) | Week 4 | Mean eFEV1 during the treatment period (mean of the last 2 weeks of the treatment period) |
| Evening Peak Expiratory Flow (ePEF) | Week 4 | Mean ePEF during the treatment period (mean of the last 2 weeks of the treatment period) |
| Total Use of Reliever | Week 4 | Mean total reliever use during the treatment period (mean of the last 2 weeks of the treatment period) |
| Night-time Asthma Symptom Score | Week 4 | Mean night-time asthma symptom score during the treatment period (mean of the last 2 weeks of the treatment period). Scores range from 0 (none) to 3 (bad). |
| Day-time Asthma Symptom Score | Week 4 | Mean day-time asthma symptom score during the treatment period (mean of the last 2 weeks of the treatment period). Scores range from 0 (none) to 3 (bad). |
| Awakenings | Week 4 | Mean percentage of awakenings due to asthma symptoms during the treatment period (mean of the last 2 weeks of the treatment period) |
| Morning Forced Expiratory Volume in 1 Second (mFEV1) | Week 4 | Mean mFEV1 during the treatment period (mean of the last 2 weeks of the treatment period) |
| Symptom Free Day | Week 4 | Mean percentage of symptom free days during the treatment period (mean of the last 2 weeks of the treatment period). A symptom-free day is defined as a day and a night with no asthma symptoms and a day and night with no awakenings due to asthma symptoms. |
| Reliever Free Day | Week 4 | Mean percentage of reliever free days during the treatment period (mean of the last 2 weeks of the treatment period). A reliever free day is defined as a day and a night with no use of as-needed medication. |
| Forced Expiratory Volume in 1 Second (FEV1) at the Clinic | Week 4 | Mean FEV1 during the treatment period (mean value at Week 4) |
| Forced Vital Capacity (FVC) at the Clinic | Week 4 | Mean FVC during the treatment period (mean value at Week 4) |
| Asthma Control Questionnaire 5 Items (ACQ5) | Week 4 | Mean ACQ5 score during the treatment period (mean value at Week 4). Scores range from 0 (good) to 6 (poor control). |
| Adverse Event (AE) | 4 weeks | Number of patients reporting at least one event |
| Asthma Control Day | Week 4 | Mean percentage of asthma control days during the treatment period (mean of the last 2 weeks of the treatment period). An asthma control day is defined as a symptom-free day with no use of reliever medication during day and night. A symptom-free day is defined as a day and a night with no asthma symptoms and a day and night with no awakenings due to asthma symptoms. |
Countries
Argentina, Brazil, Costa Rica, Poland
Participant flow
Recruitment details
510 patients enrolled, 368 were allocated to treatment and 350 completed the study. First patient entered the study on 16 September 2008 and the last patient finished the study on 13 July 2009.
Participants by arm
| Arm | Count |
|---|---|
| AZD1981 50 mg Twice Daily (Bid) AZD1981 oral tablet 50 mg, twice daily | 95 |
| AZD1981 400 mg Twice Daily (Bid) AZD1981 oral tablet 400 mg, twice daily | 90 |
| AZD1981 1000 mg Twice Daily (Bid) AZD1981 oral tablet 1000 mg, twice daily | 92 |
| Placebo placebo oral tablet, twice daily | 91 |
| Total | 368 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 5 | 4 |
| Overall Study | Palm stopped to work | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | AZD1981 50 mg Twice Daily (Bid) | AZD1981 400 mg Twice Daily (Bid) | AZD1981 1000 mg Twice Daily (Bid) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.3 Years | 43 Years | 43.5 Years | 45.7 Years | 44.35 Years |
| Sex: Female, Male Female | 27 Participants | 19 Participants | 34 Participants | 33 Participants | 113 Participants |
| Sex: Female, Male Male | 68 Participants | 71 Participants | 58 Participants | 58 Participants | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 95 | 6 / 90 | 11 / 92 | 7 / 91 |
| serious Total, serious adverse events | 0 / 95 | 0 / 90 | 1 / 92 | 1 / 91 |
Outcome results
Primary
Morning Peak Expiratory Flow (mPEF)
Mean mPEF during the treatment period (mean of the last 2 weeks of the treatment period)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Morning Peak Expiratory Flow (mPEF) | 346.42 L/min | Standard Deviation 132.7 |
| AZD1981 400 mg Twice Daily (Bid) | Morning Peak Expiratory Flow (mPEF) | 362.54 L/min | Standard Deviation 134.69 |
| AZD1981 1000 mg Twice Daily (Bid) | Morning Peak Expiratory Flow (mPEF) | 352.87 L/min | Standard Deviation 124.22 |
| Placebo | Morning Peak Expiratory Flow (mPEF) | 329.75 L/min | Standard Deviation 140.14 |
Secondary
Adverse Event (AE)
Number of patients reporting at least one event
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Adverse Event (AE) | 28 Participants |
| AZD1981 400 mg Twice Daily (Bid) | Adverse Event (AE) | 22 Participants |
| AZD1981 1000 mg Twice Daily (Bid) | Adverse Event (AE) | 33 Participants |
| Placebo | Adverse Event (AE) | 24 Participants |
Secondary
Asthma Control Day
Mean percentage of asthma control days during the treatment period (mean of the last 2 weeks of the treatment period). An asthma control day is defined as a symptom-free day with no use of reliever medication during day and night. A symptom-free day is defined as a day and a night with no asthma symptoms and a day and night with no awakenings due to asthma symptoms.
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Asthma Control Day | 10.78 Percentage of days | Standard Deviation 25.79 |
| AZD1981 400 mg Twice Daily (Bid) | Asthma Control Day | 7.48 Percentage of days | Standard Deviation 20.71 |
| AZD1981 1000 mg Twice Daily (Bid) | Asthma Control Day | 13.23 Percentage of days | Standard Deviation 26.24 |
| Placebo | Asthma Control Day | 10.08 Percentage of days | Standard Deviation 22.36 |
Secondary
Asthma Control Questionnaire 5 Items (ACQ5)
Mean ACQ5 score during the treatment period (mean value at Week 4). Scores range from 0 (good) to 6 (poor control).
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Asthma Control Questionnaire 5 Items (ACQ5) | 1.69 Scores on a scale | Full Range -2.4 |
| AZD1981 400 mg Twice Daily (Bid) | Asthma Control Questionnaire 5 Items (ACQ5) | 1.58 Scores on a scale | Full Range -2.4 |
| AZD1981 1000 mg Twice Daily (Bid) | Asthma Control Questionnaire 5 Items (ACQ5) | 1.64 Scores on a scale | Full Range -3.2 |
| Placebo | Asthma Control Questionnaire 5 Items (ACQ5) | 1.91 Scores on a scale | Full Range -2.6 |
Secondary
Awakenings
Mean percentage of awakenings due to asthma symptoms during the treatment period (mean of the last 2 weeks of the treatment period)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Awakenings | 38.59 Percentage of days | Standard Deviation 40.25 |
| AZD1981 400 mg Twice Daily (Bid) | Awakenings | 33.18 Percentage of days | Standard Deviation 38.93 |
| AZD1981 1000 mg Twice Daily (Bid) | Awakenings | 33.34 Percentage of days | Standard Deviation 37.68 |
| Placebo | Awakenings | 37.32 Percentage of days | Standard Deviation 39.51 |
Secondary
Day-time Asthma Symptom Score
Mean day-time asthma symptom score during the treatment period (mean of the last 2 weeks of the treatment period). Scores range from 0 (none) to 3 (bad).
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Day-time Asthma Symptom Score | 1.037 Scores on a scale | Standard Deviation 0.609 |
| AZD1981 400 mg Twice Daily (Bid) | Day-time Asthma Symptom Score | 0.933 Scores on a scale | Standard Deviation 0.556 |
| AZD1981 1000 mg Twice Daily (Bid) | Day-time Asthma Symptom Score | 0.995 Scores on a scale | Standard Deviation 0.552 |
| Placebo | Day-time Asthma Symptom Score | 1.105 Scores on a scale | Standard Deviation 0.645 |
Secondary
Evening Forced Expiratory Volume in 1 Second (eFEV1)
Mean eFEV1 during the treatment period (mean of the last 2 weeks of the treatment period)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Evening Forced Expiratory Volume in 1 Second (eFEV1) | 2.47 L | Standard Deviation 0.95 |
| AZD1981 400 mg Twice Daily (Bid) | Evening Forced Expiratory Volume in 1 Second (eFEV1) | 2.72 L | Standard Deviation 1.02 |
| AZD1981 1000 mg Twice Daily (Bid) | Evening Forced Expiratory Volume in 1 Second (eFEV1) | 2.63 L | Standard Deviation 0.98 |
| Placebo | Evening Forced Expiratory Volume in 1 Second (eFEV1) | 2.43 L | Standard Deviation 1.06 |
Secondary
Evening Peak Expiratory Flow (ePEF)
Mean ePEF during the treatment period (mean of the last 2 weeks of the treatment period)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Evening Peak Expiratory Flow (ePEF) | 359.83 L/min | Standard Deviation 129.23 |
| AZD1981 400 mg Twice Daily (Bid) | Evening Peak Expiratory Flow (ePEF) | 378.98 L/min | Standard Deviation 134.54 |
| AZD1981 1000 mg Twice Daily (Bid) | Evening Peak Expiratory Flow (ePEF) | 368.70 L/min | Standard Deviation 124.08 |
| Placebo | Evening Peak Expiratory Flow (ePEF) | 348.87 L/min | Standard Deviation 142.92 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) at the Clinic
Mean FEV1 during the treatment period (mean value at Week 4)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Forced Expiratory Volume in 1 Second (FEV1) at the Clinic | 2.653 L | Standard Deviation 1.051 |
| AZD1981 400 mg Twice Daily (Bid) | Forced Expiratory Volume in 1 Second (FEV1) at the Clinic | 2.739 L | Standard Deviation 1.028 |
| AZD1981 1000 mg Twice Daily (Bid) | Forced Expiratory Volume in 1 Second (FEV1) at the Clinic | 2.628 L | Standard Deviation 1.057 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at the Clinic | 2.400 L | Standard Deviation 0.945 |
Secondary
Forced Vital Capacity (FVC) at the Clinic
Mean FVC during the treatment period (mean value at Week 4)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Forced Vital Capacity (FVC) at the Clinic | 3.704 L | Standard Deviation 1.268 |
| AZD1981 400 mg Twice Daily (Bid) | Forced Vital Capacity (FVC) at the Clinic | 3.892 L | Standard Deviation 1.295 |
| AZD1981 1000 mg Twice Daily (Bid) | Forced Vital Capacity (FVC) at the Clinic | 3.546 L | Standard Deviation 1.257 |
| Placebo | Forced Vital Capacity (FVC) at the Clinic | 3.563 L | Standard Deviation 1.215 |
Secondary
Morning Forced Expiratory Volume in 1 Second (mFEV1)
Mean mFEV1 during the treatment period (mean of the last 2 weeks of the treatment period)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Morning Forced Expiratory Volume in 1 Second (mFEV1) | 2.45 L | Standard Deviation 0.99 |
| AZD1981 400 mg Twice Daily (Bid) | Morning Forced Expiratory Volume in 1 Second (mFEV1) | 2.65 L | Standard Deviation 1.03 |
| AZD1981 1000 mg Twice Daily (Bid) | Morning Forced Expiratory Volume in 1 Second (mFEV1) | 2.53 L | Standard Deviation 0.97 |
| Placebo | Morning Forced Expiratory Volume in 1 Second (mFEV1) | 2.31 L | Standard Deviation 1.05 |
Secondary
Night-time Asthma Symptom Score
Mean night-time asthma symptom score during the treatment period (mean of the last 2 weeks of the treatment period). Scores range from 0 (none) to 3 (bad).
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Night-time Asthma Symptom Score | 0.998 Scores on a scale | Standard Deviation 0.633 |
| AZD1981 400 mg Twice Daily (Bid) | Night-time Asthma Symptom Score | 0.881 Scores on a scale | Standard Deviation 0.543 |
| AZD1981 1000 mg Twice Daily (Bid) | Night-time Asthma Symptom Score | 0.912 Scores on a scale | Standard Deviation 0.594 |
| Placebo | Night-time Asthma Symptom Score | 1.008 Scores on a scale | Standard Deviation 0.614 |
Secondary
Reliever Free Day
Mean percentage of reliever free days during the treatment period (mean of the last 2 weeks of the treatment period). A reliever free day is defined as a day and a night with no use of as-needed medication.
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Reliever Free Day | 22.59 Percentage of days | Standard Deviation 34.57 |
| AZD1981 400 mg Twice Daily (Bid) | Reliever Free Day | 20.60 Percentage of days | Standard Deviation 32.01 |
| AZD1981 1000 mg Twice Daily (Bid) | Reliever Free Day | 24.13 Percentage of days | Standard Deviation 32.12 |
| Placebo | Reliever Free Day | 20.94 Percentage of days | Standard Deviation 32.97 |
Secondary
Symptom Free Day
Mean percentage of symptom free days during the treatment period (mean of the last 2 weeks of the treatment period). A symptom-free day is defined as a day and a night with no asthma symptoms and a day and night with no awakenings due to asthma symptoms.
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Symptom Free Day | 17.33 Percentage of days | Standard Deviation 32.16 |
| AZD1981 400 mg Twice Daily (Bid) | Symptom Free Day | 13.95 Percentage of days | Standard Deviation 28.35 |
| AZD1981 1000 mg Twice Daily (Bid) | Symptom Free Day | 15.56 Percentage of days | Standard Deviation 28.51 |
| Placebo | Symptom Free Day | 14.31 Percentage of days | Standard Deviation 26.28 |
Secondary
Total Use of Reliever
Mean total reliever use during the treatment period (mean of the last 2 weeks of the treatment period)
Time frame: Week 4
Population: The efficacy analysis is based on 368 total randomized patients with available data. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 50 mg Twice Daily (Bid) | Total Use of Reliever | 2.870 Number of inhalations per day | Standard Deviation 2.475 |
| AZD1981 400 mg Twice Daily (Bid) | Total Use of Reliever | 2.640 Number of inhalations per day | Standard Deviation 2.303 |
| AZD1981 1000 mg Twice Daily (Bid) | Total Use of Reliever | 2.569 Number of inhalations per day | Standard Deviation 2.21 |
| Placebo | Total Use of Reliever | 2.855 Number of inhalations per day | Standard Deviation 2.43 |