Asthma
Conditions
Keywords
Uncontrolled Asthma,, Exacerbation,, Safety
Brief summary
The purpose is to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma
Detailed description
A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study with an Optional Safety Extension Treatment Period up to 6 months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma
Interventions
DRUGAZD5069
AZD5069 oral capsules self-administered twice daily.
DRUGPlacebo
Placebo oral capsules self-administered twice daily.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 150 Years
Healthy volunteers
No
Inclusion criteria
* Men and women aged 18 years and above. Females of childbearing potential must use a highly effective contraceptive method plus a condom by their male partner. * Diagnosis of asthma for at least 12 months (GINA 2011) * Uncontrolled persistent asthma, despite treatment with medium to high dose ICS and LABA, and with a history of exacerbations during the last year * Morning prebronchodilator FEV1 of ≥30% and ≤85% predicted normal at enrolment * Daily use of medium or high dose ICS (≥fluticasone 500 µg or the equivalent daily)
Exclusion criteria
* Any clinically significant disease or disorder (including any chronic lower respiratory disease other than asthma) that may put the patient at risk or influence study results * Patients with recurrent, latent, or chronic infections * Active tuberculosis or latent tuberculosis without completion of an appropriate course of treatment or prophylactic treatment * Significant lower respiratory tract infection not resolved within 30 days prior to enrolment * Current smoker or smoking history of more than 20 pack years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of Severe Asthma Exacerbations During 6 Months | From start of treatment up to 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions | From start of treatment up to 6 months | — |
| Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms | From start of treatment up to 6 months | — |
| Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1 | Baseline (Day 0) and 2 weeks after Day 0 | Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis |
| Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 | Baseline (Day 0) and 1 month after Day 0 | Only patients with both a non-missing value at baseline and visit at one month are included in the analysis |
| Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 | Baseline (Day 0) and 2 months after Day 0 | Only patients with both a non-missing value at baseline and visit at two months are included in the analysis |
| Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 | Baseline (Day 0) and 3 months after Day 0 | Only patients with both a non-missing value at baseline and visit at three months are included in the analysis |
| Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 | Baseline (Day 0) and 4 months after Day 0 | Only patients with both a non-missing value at baseline and visit at four months are included in the analysis |
| Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 | Baseline (Day 0) and 6 months after Day 0 | Only patients with both a non-missing value at baseline and visit at six months are included in the analysis |
| Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 | Baseline (Day 0) and 2 weeks after Day 0 | Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis |
| Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 | Baseline (Day 0) and 1 month after Day 0 | Only patients with both a non-missing value at baseline and visit at one month are included in the analysis |
| Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 | Baseline (Day 0) and 2 months after Day 0 | Only patients with both a non-missing value at baseline and visit at two months are included in the analysis |
| Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 | Baseline (Day 0) and 3 months after Day 0 | Only patients with both a non-missing value at baseline and visit at three months are included in the analysis |
| Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 | Baseline (Day 0) and 4 months after Day 0 | Only patients with both a non-missing value at baseline and visit at four months are included in the analysis |
| Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 | Baseline (Day 0) and 6 months after Day 0 | Only patients with both a non-missing value at baseline and visit at six months are included in the analysis |
| Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score | Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months) | The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). |
| Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) | Baseline (Day 0) and 6 months after Day 0 | The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). |
| Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | Baseline (Day 0), Treatment Period (1,3, and 6 months) | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and \> 1.5 as marked clinically important differences for any individual domain or for the overall summary score. |
| Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | Baseline (Day 0) and 6 months after Day 0 | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and \> 1.5 as marked clinically important differences for any individual domain or for the overall summary score. |
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | — |
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56) | — |
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) | — |
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days | Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months) | — |
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | — |
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days | Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56) | — |
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days | Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) | — |
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days | Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months | — |
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | — |
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56) | — |
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84) | — |
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days | Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months) | — |
| Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms | Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28) | — |
| Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms | Baseline (last 14 days before randomization) and Treatment Period (Day 29 to Day 56) | — |
| Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms | Baseline (last 14 days before randomization) and Treatment Period (Day 57 to Day 84) | — |
| Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms | Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months) | — |
| Number of Participants With Well Controlled Asthma Weeks at Baseline | Last 2 weeks before randomization | — |
| Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months | From start of treatment up to 6 months | — |
| Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | Last 2 weeks before randomization | — |
| Number of Uncontrolled Persistent Asthma Weeks During Treatment | Day 1 to end of the 6 months treatment period | — |
| Mean Plasma Concentration of AZD5069 at Day 7 | Day 7 | — |
| Mean Plasma Concentration of AZD5069 at 1 Month | at 1 month | — |
| Number of Well Controlled Asthma Weeks During Treatment | Day 1to end of the 6 months treatment period | — |
Countries
Bulgaria, Canada, Czechia, Germany, Hungary, Mexico, Poland, Romania, Russia, Slovakia, South Africa, Ukraine, United Kingdom
Participant flow
Recruitment details
6 months double-blind study with optional safety extension for up to 6 months, were subjects continued on the treatment they were randomized to. First subject enrolled 27 Nov 2012 Last subject last visit 27 Aug 2014 1146 subjects enrolled in tot of which 506 patients were not randomized since they did not fulfilled all the inclusion conditions.
Pre-assignment details
4 weeks run-in period on background therapy prior to randomization. The discrepancy in the number of enrolled patients compared to the protocol section (n=1147) is because of a patient was in error reported by a monitor as enrolled when the patient was in effect not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| AZD5069 45 mg BID AZD5069 oral capsules self-administered twice daily | 162 |
| AZD5069 15 mg BID AZD5069 oral capsules self-administered twice daily | 156 |
| AZD5069 5 mg BID AZD5069 oral capsules self-administered twice daily | 160 |
| Placebo Placebo oral capsules self-administred twice daily | 162 |
| Total | 640 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Optional Safety Extension | Adverse Event | 0 | 4 | 0 | 1 |
| Optional Safety Extension | Other reason | 27 | 29 | 30 | 28 |
| Optional Safety Extension | Withdrawal by Subject | 2 | 0 | 1 | 2 |
| Subjects Randomized | Adverse Event | 8 | 2 | 0 | 7 |
| Subjects Randomized | Discontinuation criteria met | 4 | 2 | 2 | 0 |
| Subjects Randomized | Eligibility criteria not fulfilled | 1 | 3 | 4 | 3 |
| Subjects Randomized | Other Reason | 3 | 2 | 3 | 2 |
| Subjects Randomized | Protocol Violation | 1 | 1 | 2 | 0 |
| Subjects Randomized | Withdrawal by Subject | 5 | 5 | 5 | 5 |
Baseline characteristics
| Characteristic | AZD5069 45 mg BID | AZD5069 15 mg BID | AZD5069 5 mg BID | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 11.6 | 52 years STANDARD_DEVIATION 12.7 | 53 years STANDARD_DEVIATION 11.5 | 54 years STANDARD_DEVIATION 11.1 | 52 years STANDARD_DEVIATION 11.8 |
| FEV1 post-bronchodilator | 74.34 percentage of predicted normal | 77.95 percentage of predicted normal | 76.31 percentage of predicted normal | 72.19 percentage of predicted normal | 75.22 percentage of predicted normal |
| FEV1 pre-bronchodilator | 63.74 percentage of predicted normal | 66.35 percentage of predicted normal | 65.76 percentage of predicted normal | 61.58 percentage of predicted normal | 64.93 percentage of predicted normal |
| Reversibility | 18.73 percentage change STANDARD_DEVIATION 20.617 | 16.05 percentage change STANDARD_DEVIATION 15.58 | 18.41 percentage change STANDARD_DEVIATION 20.574 | 18.45 percentage change STANDARD_DEVIATION 16.342 | 17.93 percentage change STANDARD_DEVIATION 18.438 |
| Sex: Female, Male Female | 107 Participants | 113 Participants | 104 Participants | 120 Participants | 444 Participants |
| Sex: Female, Male Male | 55 Participants | 43 Participants | 56 Participants | 42 Participants | 196 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 | 86 / 161 | 68 / 153 | 74 / 156 | 96 / 159 |
| serious Total, serious adverse events | 14 / 161 | 8 / 153 | 7 / 156 | 13 / 159 |
Outcome results
Primary
Rate of Severe Asthma Exacerbations During 6 Months
Time frame: From start of treatment up to 6 months
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Rate of Severe Asthma Exacerbations During 6 Months | 0.31 Exacerbations per 6 month |
| AZD5069 15 mg BID | Rate of Severe Asthma Exacerbations During 6 Months | 0.31 Exacerbations per 6 month |
| AZD5069 5 mg BID | Rate of Severe Asthma Exacerbations During 6 Months | 0.26 Exacerbations per 6 month |
| Placebo | Rate of Severe Asthma Exacerbations During 6 Months | 0.20 Exacerbations per 6 month |
p-value: 0.11990% CI: [0.98, 2.49]Poisson regression
p-value: 0.14190% CI: [0.95, 2.46]Poisson Regression
p-value: 0.39790% CI: [0.79, 2.11]Poisson Regression
Secondary
Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at one month are included in the analysis
Time frame: Baseline (Day 0) and 1 month after Day 0
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 | 0.06 L |
| AZD5069 15 mg BID | Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 | 0.05 L |
| AZD5069 5 mg BID | Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 | 0.03 L |
| Placebo | Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1 | 0.03 L |
Secondary
Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at one month are included in the analysis
Time frame: Baseline (Day 0) and 1 month after Day 0
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 | 0.14 L |
| AZD5069 15 mg BID | Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 | 0.08 L |
| AZD5069 5 mg BID | Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 | 0.09 L |
| Placebo | Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1 | 0.09 L |
Secondary
Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at two months are included in the analysis
Time frame: Baseline (Day 0) and 2 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 | 0.03 L |
| AZD5069 15 mg BID | Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 | 0.04 L |
| AZD5069 5 mg BID | Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 | 0.01 L |
| Placebo | Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1 | 0.02 L |
Secondary
Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at two months are included in the analysis
Time frame: Baseline (Day 0) and 2 months after Day 0
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 | 0.13 L |
| AZD5069 15 mg BID | Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 | 0.08 L |
| AZD5069 5 mg BID | Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 | 0.07 L |
| Placebo | Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1 | 0.12 L |
Secondary
Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis
Time frame: Baseline (Day 0) and 2 weeks after Day 0
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 | 0.06 L |
| AZD5069 15 mg BID | Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 | 0.05 L |
| AZD5069 5 mg BID | Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 | 0.03 L |
| Placebo | Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1 | 0.03 L |
Secondary
Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis
Time frame: Baseline (Day 0) and 2 weeks after Day 0
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1 | 0.13 L |
| AZD5069 15 mg BID | Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1 | 0.07 L |
| AZD5069 5 mg BID | Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1 | 0.09 L |
| Placebo | Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1 | 0.12 L |
Secondary
Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at three months are included in the analysis
Time frame: Baseline (Day 0) and 3 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 | 0.04 L |
| AZD5069 15 mg BID | Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 | 0.04 L |
| AZD5069 5 mg BID | Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 | -0.00 L |
| Placebo | Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1 | -0.01 L |
Secondary
Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at three months are included in the analysis
Time frame: Baseline (Day 0) and 3 months after Day 0
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 | 0.10 L |
| AZD5069 15 mg BID | Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 | 0.11 L |
| AZD5069 5 mg BID | Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 | 0.06 L |
| Placebo | Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1 | 0.06 L |
Secondary
Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at four months are included in the analysis
Time frame: Baseline (Day 0) and 4 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 | 0.06 L |
| AZD5069 15 mg BID | Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 | 0.06 L |
| AZD5069 5 mg BID | Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 | 0.03 L |
| Placebo | Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1 | 0.03 L |
Secondary
Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at four months are included in the analysis
Time frame: Baseline (Day 0) and 4 months after Day 0
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 | 0.17 L |
| AZD5069 15 mg BID | Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 | 0.17 L |
| AZD5069 5 mg BID | Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 | 0.14 L |
| Placebo | Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1 | 0.16 L |
Secondary
Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at six months are included in the analysis
Time frame: Baseline (Day 0) and 6 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 | 0.06 L |
| AZD5069 15 mg BID | Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 | 0.02 L |
| AZD5069 5 mg BID | Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 | 0.04 L |
| Placebo | Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1 | -0.01 L |
Secondary
Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1
Only patients with both a non-missing value at baseline and visit at six months are included in the analysis
Time frame: Baseline (Day 0) and 6 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 | 0.14 L |
| AZD5069 15 mg BID | Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 | 0.09 L |
| AZD5069 5 mg BID | Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 | 0.10 L |
| Placebo | Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1 | 0.11 L |
Secondary
Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score
The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).
Time frame: Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score | -0.68 Units on a scale] |
| AZD5069 15 mg BID | Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score | -0.66 Units on a scale] |
| AZD5069 5 mg BID | Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score | -0.64 Units on a scale] |
| Placebo | Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score | -0.70 Units on a scale] |
Secondary
Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score
The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and \> 1.5 as marked clinically important differences for any individual domain or for the overall summary score.
Time frame: Baseline (Day 0), Treatment Period (1,3, and 6 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 0.50 Overall Score |
| AZD5069 15 mg BID | Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 0.46 Overall Score |
| AZD5069 5 mg BID | Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 0.52 Overall Score |
| Placebo | Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 0.52 Overall Score |
Secondary
Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days | -1.1 asthma control days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days | 1.7 asthma control days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days | 1.2 asthma control days |
| Placebo | Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days | 0.9 asthma control days |
Secondary
Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days | -0.4 Asthma symptom free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days | 1.6 Asthma symptom free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days | 1.2 Asthma symptom free days |
| Placebo | Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days | 1.1 Asthma symptom free days |
Secondary
Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms | -10.1 night time awakenings |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms | -11.1 night time awakenings |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms | -11.3 night time awakenings |
| Placebo | Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms | -8.9 night time awakenings |
Secondary
Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days | 4.0 rescue medication free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days | 8.3 rescue medication free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days | 6.8 rescue medication free days |
| Placebo | Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days | 9.5 rescue medication free days |
Secondary
Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days | -0.1 asthma control days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days | 3.5 asthma control days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days | 2.7 asthma control days |
| Placebo | Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days | 2.8 asthma control days |
Secondary
Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days | 0.2 symptom free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days | 2.6 symptom free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days | 3.4 symptom free days |
| Placebo | Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days | 3.1 symptom free days |
Secondary
Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Day 29 to Day 56)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms | -15.2 night time awakenings |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms | -19.0 night time awakenings |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms | -18.2 night time awakenings |
| Placebo | Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms | -15.2 night time awakenings |
Secondary
Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days | 10.7 rescue medication free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days | 17.6 rescue medication free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days | 15.4 rescue medication free days |
| Placebo | Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days | 16.4 rescue medication free days |
Secondary
Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days | 0.9 asthma control days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days | 4.7 asthma control days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days | 3.2 asthma control days |
| Placebo | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days | 2.9 asthma control days |
Secondary
Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days | 1.4 symptom free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days | 4.3 symptom free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days | 3.0 symptom free days |
| Placebo | Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days | 4.0 symptom free days |
Secondary
Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Day 57 to Day 84)
Population: full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms | -17.6 night time awakenings |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms | -19.8 night time awakenings |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms | -22.1 night time awakenings |
| Placebo | Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms | -16.7 night time awakenings |
Secondary
Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days | 12.3 rescue medication free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days | 19.2 rescue medication free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days | 19.8 rescue medication free days |
| Placebo | Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days | 18.7 rescue medication free days |
Secondary
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days | 1.4 asthma control days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days | 5.7 asthma control days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days | 3.9 asthma control days |
| Placebo | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days | 2.4 asthma control days |
Secondary
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days | 2.6 symptom free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days | 5.6 symptom free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days | 3.9 symptom free days |
| Placebo | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days | 4.4 symptom free days |
Secondary
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms | -22.8 night time awakenings |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms | -25.5 night time awakenings |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms | -25.3 night time awakenings |
| Placebo | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms | -21.8 night time awakenings |
Secondary
Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days
Time frame: Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months)
Population: Full Analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days | 15.8 rescue medication free days |
| AZD5069 15 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days | 23.1 rescue medication free days |
| AZD5069 5 mg BID | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days | 21.2 rescue medication free days |
| Placebo | Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days | 20.0 rescue medication free days |
Secondary
Mean Plasma Concentration of AZD5069 at 1 Month
Time frame: at 1 month
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD5069 45 mg BID | Mean Plasma Concentration of AZD5069 at 1 Month | 152.2 (nmol/L) | Geometric Coefficient of Variation 11200.64 |
| AZD5069 15 mg BID | Mean Plasma Concentration of AZD5069 at 1 Month | 76.4 (nmol/L) | Geometric Coefficient of Variation 788.17 |
| AZD5069 5 mg BID | Mean Plasma Concentration of AZD5069 at 1 Month | 25.8 (nmol/L) | Geometric Coefficient of Variation 449.02 |
Secondary
Mean Plasma Concentration of AZD5069 at Day 7
Time frame: Day 7
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD5069 45 mg BID | Mean Plasma Concentration of AZD5069 at Day 7 | 235.0 (nmol/L) | Geometric Coefficient of Variation 1525.49 |
| AZD5069 15 mg BID | Mean Plasma Concentration of AZD5069 at Day 7 | 69.9 (nmol/L) | Geometric Coefficient of Variation 717.83 |
| AZD5069 5 mg BID | Mean Plasma Concentration of AZD5069 at Day 7 | 25.4 (nmol/L) | Geometric Coefficient of Variation 511.02 |
Secondary
Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline
Time frame: Last 2 weeks before randomization
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD5069 45 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 0 uncontrolled persistent asthma weeks | 23 participants |
| AZD5069 45 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 2 uncontrolled persistent asthma weeks | 97 participants |
| AZD5069 45 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 1 uncontrolled persistent asthma weeks | 40 participants |
| AZD5069 15 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 0 uncontrolled persistent asthma weeks | 18 participants |
| AZD5069 15 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 2 uncontrolled persistent asthma weeks | 96 participants |
| AZD5069 15 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 1 uncontrolled persistent asthma weeks | 39 participants |
| AZD5069 5 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 1 uncontrolled persistent asthma weeks | 34 participants |
| AZD5069 5 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 0 uncontrolled persistent asthma weeks | 26 participants |
| AZD5069 5 mg BID | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 2 uncontrolled persistent asthma weeks | 96 participants |
| Placebo | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 0 uncontrolled persistent asthma weeks | 27 participants |
| Placebo | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 2 uncontrolled persistent asthma weeks | 95 participants |
| Placebo | Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline | 1 uncontrolled persistent asthma weeks | 36 participants |
Secondary
Number of Participants With Well Controlled Asthma Weeks at Baseline
Time frame: Last 2 weeks before randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD5069 45 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 0 Well-controlled asthma weeks Baseline | 154 participants |
| AZD5069 45 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 2 Well-controlled asthma weeks Baseline | 0 participants |
| AZD5069 45 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 1 Well-controlled asthma weeks Baseline | 6 participants |
| AZD5069 15 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 0 Well-controlled asthma weeks Baseline | 152 participants |
| AZD5069 15 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 2 Well-controlled asthma weeks Baseline | 0 participants |
| AZD5069 15 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 1 Well-controlled asthma weeks Baseline | 1 participants |
| AZD5069 5 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 1 Well-controlled asthma weeks Baseline | 4 participants |
| AZD5069 5 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 0 Well-controlled asthma weeks Baseline | 150 participants |
| AZD5069 5 mg BID | Number of Participants With Well Controlled Asthma Weeks at Baseline | 2 Well-controlled asthma weeks Baseline | 2 participants |
| Placebo | Number of Participants With Well Controlled Asthma Weeks at Baseline | 0 Well-controlled asthma weeks Baseline | 152 participants |
| Placebo | Number of Participants With Well Controlled Asthma Weeks at Baseline | 2 Well-controlled asthma weeks Baseline | 0 participants |
| Placebo | Number of Participants With Well Controlled Asthma Weeks at Baseline | 1 Well-controlled asthma weeks Baseline | 7 participants |
Secondary
Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version)
The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).
Time frame: Baseline (Day 0) and 6 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD5069 45 mg BID | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) | 72 Participants with improvement |
| AZD5069 15 mg BID | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) | 88 Participants with improvement |
| AZD5069 5 mg BID | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) | 73 Participants with improvement |
| Placebo | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) | 69 Participants with improvement |
Secondary
Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score
The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and \> 1.5 as marked clinically important differences for any individual domain or for the overall summary score.
Time frame: Baseline (Day 0) and 6 months after Day 0
Population: Full Analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD5069 45 mg BID | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 62 Participants with improvement |
| AZD5069 15 mg BID | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 68 Participants with improvement |
| AZD5069 5 mg BID | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 69 Participants with improvement |
| Placebo | Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score | 62 Participants with improvement |
Secondary
Number of Uncontrolled Persistent Asthma Weeks During Treatment
Time frame: Day 1 to end of the 6 months treatment period
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5069 45 mg BID | Number of Uncontrolled Persistent Asthma Weeks During Treatment | 11.0 uncontrolled persistent asthma weeks | Standard Deviation 10 |
| AZD5069 15 mg BID | Number of Uncontrolled Persistent Asthma Weeks During Treatment | 10.7 uncontrolled persistent asthma weeks | Standard Deviation 10.02 |
| AZD5069 5 mg BID | Number of Uncontrolled Persistent Asthma Weeks During Treatment | 10.4 uncontrolled persistent asthma weeks | Standard Deviation 9.84 |
| Placebo | Number of Uncontrolled Persistent Asthma Weeks During Treatment | 10.9 uncontrolled persistent asthma weeks | Standard Deviation 9.89 |
Secondary
Number of Well Controlled Asthma Weeks During Treatment
Time frame: Day 1to end of the 6 months treatment period
Population: Full Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5069 45 mg BID | Number of Well Controlled Asthma Weeks During Treatment | 1.7 well controlled asthma weeks | Standard Deviation 4.38 |
| AZD5069 15 mg BID | Number of Well Controlled Asthma Weeks During Treatment | 1.9 well controlled asthma weeks | Standard Deviation 4.78 |
| AZD5069 5 mg BID | Number of Well Controlled Asthma Weeks During Treatment | 2.4 well controlled asthma weeks | Standard Deviation 5.38 |
| Placebo | Number of Well Controlled Asthma Weeks During Treatment | 2.3 well controlled asthma weeks | Standard Deviation 5.27 |
Secondary
Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months
Time frame: From start of treatment up to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months | 0.04 Exacerbations per 6 month |
| AZD5069 15 mg BID | Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months | 0.02 Exacerbations per 6 month |
| AZD5069 5 mg BID | Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months | 0.02 Exacerbations per 6 month |
| Placebo | Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months | 0.02 Exacerbations per 6 month |
Secondary
Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions
Time frame: From start of treatment up to 6 months
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions | 0.54 Days |
| AZD5069 15 mg BID | Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions | 0.82 Days |
| AZD5069 5 mg BID | Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions | 0.00 Days |
| Placebo | Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions | 0.08 Days |
Secondary
Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms
Time frame: From start of treatment up to 6 months
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD5069 45 mg BID | Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms | 2.38 Days |
| AZD5069 15 mg BID | Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms | 2.43 Days |
| AZD5069 5 mg BID | Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms | 2.74 Days |
| Placebo | Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms | 1.55 Days |