Asthma
Conditions
Keywords
asthma, Upper Respiratory Tract Infection, exacerbation, Interferon, efficacy, safety, prevention
Brief summary
A study to investigate if inhaled Interferon beta-1a is safe and tolerated, and can prevent or reduce the severity of asthma attacks when administered to asthma patients at the onset of symptoms of common cold or influenza
Detailed description
The study will consist of a Pre-Treatment Phase followed by a Treatment Phase. Patients are screened and enter the Pre-Treatment phase where they remain until they develop symptoms of a common cold or the flu. During this Pre-Treatment Phase patients will be asked daily if they think they have a common cold or the flu. When the patient answers yes to the question that he/she is coming down with a common cold or the flu, arrangements are made to evaluate the patient at the study site and, if eligible, enters the Treatment Phase. Baseline assessments are performed and the patient is randomized 1:1 to receive 24 μg (metered dose) inhaled Interferon beta-1a or placebo once daily for 14 days (delivered by the I-neb® device \[Philips Respironics\]). Treatment should start as soon as possible but no later than 48 hours after the onset of the first of the common cold or flu symptoms. Patients will be assessed with regards to exacerbations and changes in respiratory symptoms and reliever medication use at home using an ePRO device. Lung function will be measured both at home by the patients and at the study site. There will be five clinical visits during the Treatment Phase and two visits after the end of treatment; efficacy and safety will be monitored until 2-3 weeks after end of treatment when a final follow-up visit will take place. The study population will comprise adult asthmatic patients on a maintenance treatment of medium to high dose inhaled corticosteroids and a second controller medication (eg, long- acting β2 agonist), with a documented history of at least two severe exacerbations within the last 24 months, of which at least one has occurred during the last 12 months, and it is suspected by the patient that these aforementioned exacerbations were triggered by an upper respiratory tract infection (ie, related to symptoms of a common cold or the flu).
Interventions
DRUGInterferon beta-1a Nebuliser solution 48 μg/mL
Interferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days
DRUGPlacebo
Placebo solution for once daily inhalation for 14 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria: 1. Provision of signed and dated written informed consent prior to any study specific procedures 2. Male or female aged 18 and above at the time of enrolment 3. History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (\>250 μg fluticasone dry powder formulation equivalents total daily dose, as defined in GINA 2014, see CSP Appendix G), and a second controller medication as recommended in the GINA guidelines (ie, LABA, leukotriene receptor antagonist or sustained release theophylline). The medium or high dose ICS plus LABA can be any combination inhaler or 2 separate inhalers. Patients must have taken ICS (\>250 μg fluticasone or the equivalent daily) plus second controller medication for at least 12 months prior to the date the informed consent is obtained, with or without another controller such as oral corticosteroids (OCS), theophylline, tiotropium, or leukotriene receptor antagonists. The maintenance treatment must have been kept at the same or at a higher level these last 12 months. 4. Proof of post-bronchodilator reversibility in FEV1 of ≥12% and ≥200 mL (Pellegrino et al 2005) documented within 5 years prior to Visit 1, or proof of a positive response to a methacholine or histamine challenge (a decrease in FEV1 by 20% \[PC20\] at ≤8 mg/mL) performed according to ATS/ERS guidelines (American Thoracic Society 2000) or proof of positive response to mannitol challenge (a decrease in FEV1 by 15% \[PD15\] at ≤635 mg) (Anderson et al 2009) documented within 5 years prior to Visit 1. If historical documentation is not available, reversibility or proof of a positive response to a methacholine, histamine or mannitol challenge must be demonstrated and documented at Visit 1 5. Must answer Yes to the question Does a cold or flu make your asthma worse? 6. To have had at least two documented severe asthma exacerbations within the last 24 months that were suspected by the patient to have been caused by a common cold or flu and To have had at least one documented severe asthma exacerbation within the last 12 months that was suspected by the patient to have been caused by a common cold or flu 7. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception. 8. Negative pregnancy test (urine) for female patients of childbearing potential 9. Motivation (in the Investigator's opinion) to complete all study visits, the ability to communicate well with the Investigator and be capable of understanding the nature of the research and its treatment including its risks and benefits 10. Ability to read and write and use the electronic devices, including demonstrating an acceptable technique when using the ePRO device, home spirometer and the I-neb
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment | Day 1 - 14 of the treatment phase. | Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations during the 14 day treatment phase following the onset of an URTI in asthmatic patients. A severe exacerbation was defined as worsening asthma symptoms and 1. use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or 2. an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or 3. an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The number of patients with severe asthma exacerbations with onset during the treatment phase is presented for each treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Day 1 of treatment phase up to 30 days post-randomisation. | Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing moderate exacerbations within 7, 14 and 30 days after the start of treatment (Day 1). A moderate exacerbation was defined as a temporary increase in maintenance therapy in order to prevent a severe event supported by a sustained (2 or more days) worsening in at least one key control metric, including asthma score, rescue use, night time awakening or morning peak expiratory flow. The numbers of patients with moderate exacerbations with onset during Days 1 - 7, Days 1 - 14 and Days 1 - 30 are presented for each treatment group. With respect to the Day 1-7 analysis, the model did not converge so the analysis could not be performed. |
| Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation | From Day 1 of treatment phase up to 30 days post-randomisation. | The time to first event was calculated as start date of events - date of randomisation + 1. Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed. The median time to first exacerbation was not calculated in either treatment group due to low numbers of events. |
| Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation | From Day 1 of treatment phase up to 30 days post-randomisation. | The time to first event was calculated as start date of events - date of randomisation + 1. Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed. The median time to first exacerbation was not calculated in either treatment group due to low numbers of events. |
| Duration of Moderate or Severe Exacerbations | Day 1 of treatment phase up to 30 days post-randomisation. | The duration of each individual moderate or severe exacerbation was calculated as: Cessation date of exacerbation - Start date of exacerbation + 1. The start date of a severe exacerbation was defined as the start date of systemic corticosteroids or increase of systemic corticosteroids or emergency room visit or hospital admission, whichever occurred first. The stop date was defined as the last day of systemic corticosteroids/increase of systemic corticosteroids or hospital discharge, whichever occurred last. The start date of a moderate exacerbation was defined as the first day of increase in temporary maintenance therapy. The stop date was defined as the last day of this treatment. The mean duration of moderate or severe exacerbations is presented for each treatment group. |
| Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | From baseline up to 30 days after start of treatment phase. | The ACQ-6 consists of 6 questions to assess asthma control, each question measured on a 7-point scale scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 total score is computed as the un-weighted mean of the responses to the 6 questions. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The change from baseline at Visit 4 (Day 7 +/- 1), at Visit 6 (Day 14 +/- 1) and at Visit 8 (Day 30) is presented for the total score and for each of the 6 questions. |
| AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | From baseline up to 30 days after start of treatment phase. | Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary on a daily basis. Symptoms were recorded using a scale of 0 to 3 where 0 indicates no asthma symptoms up to an absolute score of 3. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The total daily asthma symptom score was calculated by taking the sum of the night-time and daytime asthma scores recorded each day. The outcome variable is the area under the curve (AUC) for change from baseline in day-time, night-time and total daily asthma symptom scores over Days 1-14, Days 1-7, Days 8-14 and Days 15-30. |
| Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation | Day 1 of treatment phase up to 30 days post-randomisation. | Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations within 7 and 30 days after the start of treatment (Day 1). A severe exacerbation was defined as worsening asthma symptoms and 1. use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or 2. an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or 3. an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The numbers of patients with severe asthma exacerbations with onset during Days 1 - 7 and Days 1 - 30 are presented for each treatment group. |
| Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days | From baseline up to 30 days after start of treatment phase. | The AQLQ(S) was used to assess health-related quality of life and consisted of 32 questions. Patients were asked to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The questions were allocated to 4 domains assessing: 1. activity limitation, 2. symptoms, 3. emotional function, and 4. environmental stimuli The overall score was calculated as the mean of the responses to all questions. The mean change in overall score from baseline at Visit 6 (Day 14+/-1) and Visit 8 (Day 30) are presented. |
| AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days | From baseline up to Day 14 of treatment phase. | Patients recorded the number of reliever medication inhalations taken twice daily in the Asthma Daily Diary. The number of inhalations taken between the morning and evening lung function assessments were recorded in the evening. The number of inhalations taken between the evening and morning lung function assessments were recorded in the morning. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The AUC for change from baseline over Days 1-14 (inclusive of Days 1 and 14) is presented. |
| AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | From baseline up to 30 days after start of treatment phase. | Patients measured morning PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. |
| AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | From baseline up to 30 days after start of treatment phase. | Patients measured morning FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. |
| AUC for Change in the Evening PEF From Baseline to up to 30 Days | From baseline up to 30 days after start of treatment phase. | Patients measured evening PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. |
| AUC for Change in the Evening FEV1 From Baseline up to 30 Days | From baseline up to 30 days after start of treatment phase. | Patients measured evening FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. |
| Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days | From baseline up to 30 days after start of treatment phase. | Night-time awakenings due to asthma symptoms were recorded by the patient in the Asthma Daily Diary each morning by answering the question whether he/she woke up during the night due to asthma symptoms with a 'yes' or 'no' response. Biweekly means were calculated as the percentages of times the subject answered 'yes' over a period of 14 sequential days. Biweekly means are presented for the periods over Days 2-15 and Days 16-30. |
Countries
Argentina, Australia, Colombia, France, South Korea, Spain, United Kingdom
Participant flow
Recruitment details
First patient enrolled: 21 July 2015; Last Patient Last Visit: 24 November 2016. The study was performed at 39 sites in 7 countries including Argentina, Australia, Colombia, France, South Korea, Spain and the United Kingdom.
Pre-assignment details
349 patients enrolled (signed informed consent) and 228 were not randomised. 121 patients met randomisation criteria and entered the pre-treatment phase. Patients were treated after developing symptoms of an upper respiratory tract infection (URTI) if they met all the inclusion criteria and none of the exclusion criteria for the treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| AZD9412 Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase.
Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI.
Patients randomised to the AZD9412 group received 6 MIU (24 mcg metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device.
Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home. | 61 |
| Placebo Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI.
Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device.
Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home. | 60 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Phase | Adverse Event | 2 | 2 |
| Treatment Phase | Incorrect randomisation | 1 | 0 |
| Treatment Phase | Investigator and Sponsor decision | 0 | 1 |
Baseline characteristics
| Characteristic | AZD9412 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 12.95 | 47.7 years STANDARD_DEVIATION 14.1 | 47.7 years STANDARD_DEVIATION 13.48 |
| Sex: Female, Male Female | 48 Participants | 43 Participants | 91 Participants |
| Sex: Female, Male Male | 13 Participants | 17 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 61 | 20 / 60 |
| serious Total, serious adverse events | 3 / 61 | 0 / 60 |
Outcome results
Primary
Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment
Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations during the 14 day treatment phase following the onset of an URTI in asthmatic patients. A severe exacerbation was defined as worsening asthma symptoms and 1. use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or 2. an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or 3. an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The number of patients with severe asthma exacerbations with onset during the treatment phase is presented for each treatment group.
Time frame: Day 1 - 14 of the treatment phase.
Population: The Intention to treat (ITT) analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD9412 | Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment | 7 Participants |
| Placebo | Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment | 5 Participants |
Comparison: Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.p-value: 0.64595% CI: [0.43, 3.85]log-binomial regression model
Secondary
AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days
Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary on a daily basis. Symptoms were recorded using a scale of 0 to 3 where 0 indicates no asthma symptoms up to an absolute score of 3. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The total daily asthma symptom score was calculated by taking the sum of the night-time and daytime asthma scores recorded each day. The outcome variable is the area under the curve (AUC) for change from baseline in day-time, night-time and total daily asthma symptom scores over Days 1-14, Days 1-7, Days 8-14 and Days 15-30.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 1-14 | -0.20 Units on Scale | Standard Error 0.16 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 1-7 | -0.11 Units on Scale | Standard Error 0.13 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 8-14 | -0.40 Units on Scale | Standard Error 0.15 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 15-30 | -0.77 Units on Scale | Standard Error 0.16 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 1-14 | -0.22 Units on Scale | Standard Error 0.07 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 1-7 | -0.17 Units on Scale | Standard Error 0.06 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 8-14 | -0.23 Units on Scale | Standard Error 0.07 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 15-30 | -0.44 Units on Scale | Standard Error 0.07 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 1-14 | -0.17 Units on Scale | Standard Error 0.07 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 1-7 | -0.10 Units on Scale | Standard Error 0.06 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 8-14 | -0.20 Units on Scale | Standard Error 0.07 |
| AZD9412 | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 15-30 | -0.44 Units on Scale | Standard Error 0.09 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 8-14 | -0.17 Units on Scale | Standard Error 0.08 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 1-14 | -0.31 Units on Scale | Standard Error 0.16 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 8-14 | -0.27 Units on Scale | Standard Error 0.07 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 1-7 | -0.22 Units on Scale | Standard Error 0.13 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 1-7 | -0.09 Units on Scale | Standard Error 0.07 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 8-14 | -0.41 Units on Scale | Standard Error 0.16 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 15-30 | -0.41 Units on Scale | Standard Error 0.07 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Total asthma score, Days 15-30 | -0.77 Units on Scale | Standard Error 0.16 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 15-30 | -0.39 Units on Scale | Standard Error 0.09 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 1-14 | -0.26 Units on Scale | Standard Error 0.07 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Night-time asthma score, Days 1-14 | -0.16 Units on Scale | Standard Error 0.08 |
| Placebo | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days | Daytime asthma score, Days 1-7 | -0.17 Units on Scale | Standard Error 0.06 |
Comparison: Analysis of AUC for change from baseline in total score over Days 1-14.p-value: 0.51695% CI: [-0.23, 0.45]ANCOVA
Comparison: Analysis of AUC for change from baseline in total score over Days 1-7.p-value: 0.41795% CI: [-0.16, 0.37]ANCOVA
Comparison: Analysis of AUC for change from baseline in total score over Days 8-14.p-value: 0.95495% CI: [-0.34, 0.36]ANCOVA
Comparison: Analysis of AUC for change from baseline in total score over Days 15-30.p-value: 0.98595% CI: [-0.35, 0.35]ANCOVA
Secondary
AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days
Patients recorded the number of reliever medication inhalations taken twice daily in the Asthma Daily Diary. The number of inhalations taken between the morning and evening lung function assessments were recorded in the evening. The number of inhalations taken between the evening and morning lung function assessments were recorded in the morning. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The AUC for change from baseline over Days 1-14 (inclusive of Days 1 and 14) is presented.
Time frame: From baseline up to Day 14 of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9412 | AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days | -0.12 Inhalations | Standard Error 0.46 |
| Placebo | AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days | -0.67 Inhalations | Standard Error 0.48 |
Comparison: Analysis of AUC for change from baseline over Days 1-14.p-value: 0.30995% CI: [-0.51, 1.59]ANCOVA
Secondary
AUC for Change in the Evening FEV1 From Baseline up to 30 Days
Patients measured evening FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 1-14 | -0.01 litres | Standard Error 0.07 |
| AZD9412 | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 8-14 | -0.02 litres | Standard Error 0.07 |
| AZD9412 | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 1-7 | 0.01 litres | Standard Error 0.07 |
| AZD9412 | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 15-30 | 0.02 litres | Standard Error 0.08 |
| Placebo | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 15-30 | -0.08 litres | Standard Error 0.08 |
| Placebo | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 1-14 | -0.07 litres | Standard Error 0.07 |
| Placebo | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 1-7 | -0.03 litres | Standard Error 0.07 |
| Placebo | AUC for Change in the Evening FEV1 From Baseline up to 30 Days | Days 8-14 | -0.08 litres | Standard Error 0.07 |
Comparison: Analysis of AUC for change from baseline over Days 1-14.p-value: 0.28795% CI: [-0.05, 0.16]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 1-7.p-value: 0.45795% CI: [-0.06, 0.14]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 8-14.p-value: 0.31595% CI: [-0.05, 0.16]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 15-30.p-value: 0.13495% CI: [-0.03, 0.22]ANCOVA
Secondary
AUC for Change in the Evening PEF From Baseline to up to 30 Days
Patients measured evening PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 1-14 | 10.96 l/min | Standard Error 12.58 |
| AZD9412 | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 1-7 | 8.78 l/min | Standard Error 9.87 |
| AZD9412 | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 8-14 | 8.49 l/min | Standard Error 13.09 |
| AZD9412 | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 15-30 | 11.88 l/min | Standard Error 15.7 |
| Placebo | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 15-30 | -5.25 l/min | Standard Error 15.13 |
| Placebo | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 1-14 | -0.73 l/min | Standard Error 11.88 |
| Placebo | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 8-14 | -2.66 l/min | Standard Error 12.55 |
| Placebo | AUC for Change in the Evening PEF From Baseline to up to 30 Days | Days 1-7 | -2.41 l/min | Standard Error 9.3 |
Comparison: Analysis of AUC for change from baseline over Days 1-14.p-value: 0.21195% CI: [-6.76, 30.14]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 1-7.p-value: 0.12595% CI: [-3.18, 25.56]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 8-14.p-value: 0.27795% CI: [-9.08, 31.36]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 15-30.p-value: 0.16195% CI: [-6.92, 41.18]ANCOVA
Secondary
AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days
Patients measured morning FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 1-14 | -0.00 litres | Standard Error 0.08 |
| AZD9412 | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 1-7 | 0.10 litres | Standard Error 0.06 |
| AZD9412 | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 8-14 | -0.03 litres | Standard Error 0.08 |
| AZD9412 | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 15-30 | 0.15 litres | Standard Error 0.09 |
| Placebo | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 15-30 | 0.04 litres | Standard Error 0.08 |
| Placebo | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 1-14 | -0.08 litres | Standard Error 0.08 |
| Placebo | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 8-14 | -0.09 litres | Standard Error 0.08 |
| Placebo | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days | Days 1-7 | 0.02 litres | Standard Error 0.06 |
Comparison: Analysis of AUC for change from baseline over Days 1-14.p-value: 0.16195% CI: [-0.03, 0.17]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 1-7.p-value: 0.08795% CI: [-0.01, 0.17]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 8-14.p-value: 0.2895% CI: [-0.05, 0.16]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 15-30.p-value: 0.08695% CI: [-0.02, 0.24]ANCOVA
Secondary
AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days
Patients measured morning PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 1-14 | 9.56 litres/minute (l/min) | Standard Error 14.02 |
| AZD9412 | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 1-7 | 19.66 litres/minute (l/min) | Standard Error 9.66 |
| AZD9412 | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 8-14 | 7.03 litres/minute (l/min) | Standard Error 15.9 |
| AZD9412 | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 15-30 | 32.75 litres/minute (l/min) | Standard Error 15.35 |
| Placebo | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 15-30 | 13.49 litres/minute (l/min) | Standard Error 14.82 |
| Placebo | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 1-14 | -7.42 litres/minute (l/min) | Standard Error 13.91 |
| Placebo | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 8-14 | -7.35 litres/minute (l/min) | Standard Error 15.8 |
| Placebo | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days | Days 1-7 | 0.31 litres/minute (l/min) | Standard Error 9.11 |
Comparison: Analysis of AUC for change from baseline over Days 1-14.p-value: 0.05995% CI: [-0.63, 34.6]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 1-7.p-value: 0.0195% CI: [4.66, 34.05]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 8-14.p-value: 0.15395% CI: [-5.44, 34.2]ANCOVA
Comparison: Analysis of AUC for change from baseline over Days 15-30.p-value: 0.09695% CI: [-3.44, 41.97]ANCOVA
Secondary
Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6)
The ACQ-6 consists of 6 questions to assess asthma control, each question measured on a 7-point scale scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 total score is computed as the un-weighted mean of the responses to the 6 questions. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The change from baseline at Visit 4 (Day 7 +/- 1), at Visit 6 (Day 14 +/- 1) and at Visit 8 (Day 30) is presented for the total score and for each of the 6 questions.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | ACQ-6 Total Score, Visit 4 | 0.02 Units on a Scale | Standard Error 0.11 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | ACQ-6 Total Score, Visit 6 | -0.15 Units on a Scale | Standard Error 0.14 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | ACQ-6 Total Score, Visit 8 | -0.42 Units on a Scale | Standard Error 0.15 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q1: Woken by Asthma, Visit 4 | 0.09 Units on a Scale | Standard Error 0.18 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q1: Woken by Asthma, Visit 6 | 0.15 Units on a Scale | Standard Error 0.2 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q1: Woken by Asthma, Visit 8 | -0.50 Units on a Scale | Standard Error 0.18 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q2: Symptoms at Awakening, Visit 4 | 0.06 Units on a Scale | Standard Error 0.18 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q2: Symptoms at Awakening, Visit 6 | -0.40 Units on a Scale | Standard Error 0.16 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q2: Symptoms at Awakening, Visit 8 | -0.76 Units on a Scale | Standard Error 0.19 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q3: Limited in Activities, Visit 4 | 0.04 Units on a Scale | Standard Error 0.15 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q3: Limited in Activities, Visit 6 | -0.12 Units on a Scale | Standard Error 0.17 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q3: Limited in Activities, Visit 8 | -0.43 Units on a Scale | Standard Error 0.18 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q4: Shortness of Breath, Visit 4 | -0.13 Units on a Scale | Standard Error 0.15 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q4: Shortness of Breath, Visit 6 | -0.34 Units on a Scale | Standard Error 0.19 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q4: Shortness of Breath, Visit 8 | -0.46 Units on a Scale | Standard Error 0.18 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q5: Wheeze, Visit 4 | 0.13 Units on a Scale | Standard Error 0.17 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q5: Wheeze, Visit 6 | -0.17 Units on a Scale | Standard Error 0.17 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q5: Wheeze, Visit 8 | -0.33 Units on a Scale | Standard Error 0.21 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q6: Puffs of Short-Acting Bronchodilator; Visit 4 | 0.06 Units on a Scale | Standard Error 0.13 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q6: Puffs of Short-Acting Bronchodilator; Visit 6 | 0.07 Units on a Scale | Standard Error 0.14 |
| AZD9412 | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q6: Puffs of Short-Acting Bronchodilator; Visit 8 | 0.04 Units on a Scale | Standard Error 0.14 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q3: Limited in Activities, Visit 6 | 0.16 Units on a Scale | Standard Error 0.18 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | ACQ-6 Total Score, Visit 4 | -0.07 Units on a Scale | Standard Error 0.12 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q6: Puffs of Short-Acting Bronchodilator; Visit 4 | 0.00 Units on a Scale | Standard Error 0.14 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | ACQ-6 Total Score, Visit 6 | -0.21 Units on a Scale | Standard Error 0.14 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q3: Limited in Activities, Visit 8 | -0.33 Units on a Scale | Standard Error 0.18 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | ACQ-6 Total Score, Visit 8 | -0.35 Units on a Scale | Standard Error 0.15 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q5: Wheeze, Visit 6 | -0.17 Units on a Scale | Standard Error 0.18 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q1: Woken by Asthma, Visit 4 | -0.09 Units on a Scale | Standard Error 0.18 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q4: Shortness of Breath, Visit 4 | -0.11 Units on a Scale | Standard Error 0.16 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q1: Woken by Asthma, Visit 6 | -0.28 Units on a Scale | Standard Error 0.21 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q6: Puffs of Short-Acting Bronchodilator; Visit 8 | -0.03 Units on a Scale | Standard Error 0.14 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q1: Woken by Asthma, Visit 8 | -0.32 Units on a Scale | Standard Error 0.18 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q4: Shortness of Breath, Visit 6 | -0.38 Units on a Scale | Standard Error 0.21 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q2: Symptoms at Awakening, Visit 4 | -0.17 Units on a Scale | Standard Error 0.18 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q5: Wheeze, Visit 8 | -0.42 Units on a Scale | Standard Error 0.21 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q2: Symptoms at Awakening, Visit 6 | -0.33 Units on a Scale | Standard Error 0.17 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q4: Shortness of Breath, Visit 8 | -0.37 Units on a Scale | Standard Error 0.19 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q2: Symptoms at Awakening, Visit 8 | -0.47 Units on a Scale | Standard Error 0.19 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q6: Puffs of Short-Acting Bronchodilator; Visit 6 | -0.11 Units on a Scale | Standard Error 0.15 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q3: Limited in Activities, Visit 4 | 0.06 Units on a Scale | Standard Error 0.15 |
| Placebo | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) | Q5: Wheeze, Visit 4 | 0.08 Units on a Scale | Standard Error 0.17 |
Comparison: Analysis of change from baseline in total score at Visit 4.p-value: 0.49595% CI: [-0.17, 0.35]ANCOVA
Comparison: Analysis of change from baseline in total score at Visit 6.p-value: 0.71595% CI: [-0.26, 0.38]ANCOVA
Comparison: Analysis of change from baseline in total score at Visit 8.p-value: 0.68795% CI: [-0.42, 0.28]ANCOVA
Secondary
Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days
The AQLQ(S) was used to assess health-related quality of life and consisted of 32 questions. Patients were asked to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The questions were allocated to 4 domains assessing: 1. activity limitation, 2. symptoms, 3. emotional function, and 4. environmental stimuli The overall score was calculated as the mean of the responses to all questions. The mean change in overall score from baseline at Visit 6 (Day 14+/-1) and Visit 8 (Day 30) are presented.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days | Overall Score Visit 6 | 0.28 Units on Scale | Standard Error 0.13 |
| AZD9412 | Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days | Overall Score Visit 8 | 0.43 Units on Scale | Standard Error 0.16 |
| Placebo | Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days | Overall Score Visit 6 | 0.35 Units on Scale | Standard Error 0.14 |
| Placebo | Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days | Overall Score Visit 8 | 0.53 Units on Scale | Standard Error 0.16 |
Comparison: Analysis of change from baseline in overall score at Visit 6.p-value: 0.6695% CI: [-0.38, 0.24]ANCOVA
Comparison: Analysis of change from baseline in overall score at Visit 8.p-value: 0.62495% CI: [-0.48, 0.29]ANCOVA
Secondary
Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days
Night-time awakenings due to asthma symptoms were recorded by the patient in the Asthma Daily Diary each morning by answering the question whether he/she woke up during the night due to asthma symptoms with a 'yes' or 'no' response. Biweekly means were calculated as the percentages of times the subject answered 'yes' over a period of 14 sequential days. Biweekly means are presented for the periods over Days 2-15 and Days 16-30.
Time frame: From baseline up to 30 days after start of treatment phase.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~Patients with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD9412 | Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days | Days 2-15 | 22.3 Percentage of 'yes' responses | Standard Deviation 30.42 |
| AZD9412 | Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days | Days 16-30 | 15.2 Percentage of 'yes' responses | Standard Deviation 26.79 |
| Placebo | Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days | Days 2-15 | 24.8 Percentage of 'yes' responses | Standard Deviation 29.77 |
| Placebo | Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days | Days 16-30 | 15.9 Percentage of 'yes' responses | Standard Deviation 26.34 |
Secondary
Duration of Moderate or Severe Exacerbations
The duration of each individual moderate or severe exacerbation was calculated as: Cessation date of exacerbation - Start date of exacerbation + 1. The start date of a severe exacerbation was defined as the start date of systemic corticosteroids or increase of systemic corticosteroids or emergency room visit or hospital admission, whichever occurred first. The stop date was defined as the last day of systemic corticosteroids/increase of systemic corticosteroids or hospital discharge, whichever occurred last. The start date of a moderate exacerbation was defined as the first day of increase in temporary maintenance therapy. The stop date was defined as the last day of this treatment. The mean duration of moderate or severe exacerbations is presented for each treatment group.
Time frame: Day 1 of treatment phase up to 30 days post-randomisation.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.~The number of patients in the analysis are those with at least 1 exacerbation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9412 | Duration of Moderate or Severe Exacerbations | 10 Days | Standard Deviation 7.7 |
| Placebo | Duration of Moderate or Severe Exacerbations | 8 Days | Standard Deviation 4.5 |
Secondary
Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation
Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing moderate exacerbations within 7, 14 and 30 days after the start of treatment (Day 1). A moderate exacerbation was defined as a temporary increase in maintenance therapy in order to prevent a severe event supported by a sustained (2 or more days) worsening in at least one key control metric, including asthma score, rescue use, night time awakening or morning peak expiratory flow. The numbers of patients with moderate exacerbations with onset during Days 1 - 7, Days 1 - 14 and Days 1 - 30 are presented for each treatment group. With respect to the Day 1-7 analysis, the model did not converge so the analysis could not be performed.
Time frame: Day 1 of treatment phase up to 30 days post-randomisation.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD9412 | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Days 1 - 7 | 0 Participants |
| AZD9412 | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Days 1 - 14 | 1 Participants |
| AZD9412 | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Days 1 - 30 | 1 Participants |
| Placebo | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Days 1 - 7 | 1 Participants |
| Placebo | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Days 1 - 14 | 1 Participants |
| Placebo | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation | Days 1 - 30 | 1 Participants |
Comparison: Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.p-value: 0.94495% CI: [0.08, 15.79]log-binomial regression model
Comparison: Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.p-value: 0.94495% CI: [0.08, 15.79]log-binomial regression model
Secondary
Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation
Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations within 7 and 30 days after the start of treatment (Day 1). A severe exacerbation was defined as worsening asthma symptoms and 1. use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or 2. an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or 3. an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The numbers of patients with severe asthma exacerbations with onset during Days 1 - 7 and Days 1 - 30 are presented for each treatment group.
Time frame: Day 1 of treatment phase up to 30 days post-randomisation.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD9412 | Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation | Days 1 - 7 | 4 Participants |
| AZD9412 | Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation | Days 1 - 30 | 8 Participants |
| Placebo | Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation | Days 1 - 7 | 2 Participants |
| Placebo | Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation | Days 1 - 30 | 6 Participants |
Comparison: Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.p-value: 0.41195% CI: [0.39, 9.89]log-binomial regression model
Comparison: Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.p-value: 0.65995% CI: [0.46, 3.41]log-binomial regression model
Secondary
Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation
The time to first event was calculated as start date of events - date of randomisation + 1. Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed. The median time to first exacerbation was not calculated in either treatment group due to low numbers of events.
Time frame: From Day 1 of treatment phase up to 30 days post-randomisation.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD9412 | Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation | NA Days |
| Placebo | Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation | NA Days |
Comparison: Analysis of time to first moderate exacerbation within 30 days of treatment start.p-value: 0.97395% CI: [0.07, 16.78]Regression, Cox
Secondary
Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation
The time to first event was calculated as start date of events - date of randomisation + 1. Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed. The median time to first exacerbation was not calculated in either treatment group due to low numbers of events.
Time frame: From Day 1 of treatment phase up to 30 days post-randomisation.
Population: The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD9412 | Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation | NA Days |
| Placebo | Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation | NA Days |
Comparison: Analysis of time to first severe exacerbation within 30 days of treatment start.p-value: 0.63495% CI: [0.45, 3.77]Regression, Cox