A study in asthma patients to evaluate efficacy, safety and tolerability of 14 days once daily inhaled Interferon beta-1a after the onset of symptoms of an upper respiratory tract infection - INEXAS

Study identifier:D6230C00001

ClinicalTrials.gov identifier:NCT02491684

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A randomized, double-blind, placebo-controlled, parallel group, multi-centre Phase IIa study in asthma patients comparing the efficacy and safety of once daily inhaled Interferon beta-1a to placebo, administered for 14 days after the onset of symptoms of an upper respiratory tract infection for the prevention of severe exacerbations

Medical condition

asthma

Phase

Phase 2

Healthy volunteers

Study drug

Interferon beta-1a Nebuliser solution 48 μg/mL, Placebo

Sex

All

Actual Enrollment

121

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 21 Jul 2015

Primary Completion Date: 24 Nov 2016

Study Completion Date: 24 Nov 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Prevention

Verification:

Verified 01 Jan 2019 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

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 exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and staff at third party vendors or staff at the study sites)
2. Previous randomization to treatment in the present study
3. Any condition, including findings in the medical history or in the pre-study assessments that, in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct or evaluation
4. Lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis, allergic bronchopulmonary aspergillosis, active tuberculosis). Patients with CT or chest X-ray findings indicating bronchiectasis which in the opinion of the Investigator are not clinically significant may be enrolled at the discretion of the Investigator
5. Patients with ≥4 severe exacerbations during the last 12 months that the patient suspected were triggered by something else than an upper respiratory tract infection
6. Current participation in another clinical trial or participation in a clinical trial where the patient has received a dose of a test product (IMP) within 12 weeks prior to entry into the study for small molecules and within 12 months prior to entry into the study for biologicals, or 5 times the half-life (whichever is the longest) of the biologic or small molecule IMP
7. Patients who currently have, or have had within the past 3 months, any significant underlying medical condition(s) that could impact interpretation of results eg, infections, haematological disease, malignancy, renal, hepatic, coronary heart disease or other cardiovascular disease, including arrhythmias, endocrinological or gastrointestinal disease
8. Abnormal vital signs, after at least 10 minutes supine rest, defined as any of the following:
∀ In patients < 60 years old, systolic blood pressure <90 mmHg or ≥150 mmHg
∀ In patients ≥ 60 years old, systolic blood pressure <90 mmHg or ≥160 mmHg
∀ Diastolic blood pressure <50 mmHg or ≥100 mmHg
∀ HR <45 or >95 beats per minute
9. Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, as considered by the Investigator, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology (particularly in the protocol defined primary lead) or left ventricular hypertrophy
10. Prolonged QTcF >450 ms (for both gender) or shortened QTcF <340 ms or family history of long QT syndrome
11. PR(PQ) interval shortening <120ms (PR<120 ms but >110 ms is acceptable if there is no evidence of ventricular pre-excitation).
12. PR(PQ) interval prolongation (>240ms), intermittent second or third degree AV
block, or AV dissociation
13. QRS duration >120ms including persistent or intermittent bundle branch block
14. Patients with implantable cardiac defibrillator (ICD) or a permanent pacemaker and patients with symptomatic ventricular and / or atrial tachyarrhythmias
15. Patients with unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society (CSS) class II or a myocardial infarction or stroke within 6 months
16. History of hospitalization within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association (NYHA) class II
17. History of hypersensitivity to natural or recombinant Interferon beta-1a or to any of the drug preparation excipients
18. Received any marketed biologic agent (eg, omalizumab) within 12 months or
5 times the half-life (whichever is the longer) of the agent prior to enrolment
19. Significant history of depressive disorder or suicidal ideation. Specifically; individuals with current severe depression (ie, a low mood, which pervades all aspects of life and an inability to experience pleasure in activities that formerly were enjoyed); individuals with a past history of depression that required hospitalization or referral to psychiatric services in the past 5 years; individuals who currently feel suicidal or have attempted suicide in the past
20. History of epilepsy or seizures after the age of 5 years, other than febrile childhood seizure(s)
21. History of drug or alcohol abuse within 12 months prior to enrolment
22. Patients who have hepatic serum enzyme levels ≥2.5 times the normal range
23. Positive test for serum hepatitis B surface antigen, hepatitis C antibody, or HIV
24. Patients with a smoking history of ≥20 pack-years (1 pack year = 20 cigarettes smoked per day for one year)
25. Female who is breast-feeding, pregnant (verified by urine dipstick pregnancy test)
or intends to become pregnant during the study
26. Patients who are unable to demonstrate an acceptable spirometry technique
27. Patients that have previously been included in studies evaluating the investigational medicinal product

Location

Research Site

Nottingham, United Kingdom, NG5 1PB

Location

Research Site

CABA, Argentina, C1425BEN

Location

Research Site

Bogotá, Colombia, 110311

Location

Research Site

Bogota, Colombia

Location

Research Site

Southampton, United Kingdom, SO9 4XY

Location

Research Site

Bradford, United Kingdom, BD9 6RJ

Location

Research Site

Lancaster, United Kingdom, LA1 4RP

Location

Research Site

Barcelona, Spain, 08003

Arms	Assigned Interventions
Placebo Comparator: Placebo (matching) Placebo, once daily inhalation for 14 days	Drug: Placebo Placebo solution for once daily inhalation for 14 days
Experimental: Interferon beta-1a Interferon beta-1a, 24 μg (metered dose) once daily inhalation for 14 days	Drug: Interferon beta-1a Nebuliser solution 48 μg/mL Interferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
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 Million International Units (MIU) (24 micrograms [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 electronic Patient Reported Outcome (ePRO) device at home.
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.

Description

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 Million International Units (MIU) (24 micrograms [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 electronic Patient Reported Outcome (ePRO) device at home.

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.

Participant Flow for 2 periods

Period 1: Pre-treatment Phase

	AZD9412	Placebo
STARTED	61	60
COMPLETED	61	60
NOT COMPLETED	0	0

Period 2: Treatment Phase

	AZD9412	Placebo
STARTED	61	60
COMPLETED	58	57
NOT COMPLETED	3	3
Adverse Event	2	2
Incorrect randomisation	1	0
Investigator and Sponsor decision	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
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.
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.

Description

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.

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.

Baseline Measures

	AZD9412	Placebo	Total
Number of Participants [units: Participants]	61	60	121
Age Continuous [units: years] Mean ± Standard Deviation	47.8 ± 12.95	47.7 ± 14.10	47.7 ± 13.48
Sex: Female, Male [units: Participants]
Female	48	43	91
Male	13	17	30

Outcome Measures

1. Primary Outcome Measure: Proportion of patients with a severe asthma exacerbation during 14 days of treatment [ Time Frame: Day 1 - 14 of the treatment phase. ]

Measure Type	Primary
Measure Name	Proportion of patients with a severe asthma exacerbation during 14 days of treatment
Measure Description	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 a) 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 b) an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or c) 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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.
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.

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Proportion of patients with a severe asthma exacerbation during 14 days of treatment [units: Participants]	7	5

Statistical Analysis 1 for Proportion of patients with a severe asthma exacerbation during 14 days of treatment

Groups^[1]	All groups
Method^[3]	Other [log-binomial regression model]
P-Value^[4]	0.645
Other^[5]	1.29
95% Confidence Interval	( 0.43 to 3.85 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The ratio of proportions was calculated by back-transforming the estimated treatment effect.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

2. Secondary Outcome Measure: Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation [ Time Frame: Day 1 of treatment phase up to 30 days post-randomisation. ]

Measure Type	Secondary
Measure Name	Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation
Measure Description	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 a) 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 b) an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or c) 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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.
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.

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation [units: Participants]
Days 1 - 7	4	2
Days 1 - 30	8	6

Statistical Analysis 1 for Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation

Groups^[1]	All groups
Method^[3]	Other [log-binomial regression model]
P-Value^[4]	0.411
Other^[5]	1.97
95% Confidence Interval	( 0.39 to 9.89 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The ratio of proportions was calculated by back-transforming the estimated treatment effect.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo for Days 1 - 7

Statistical Analysis 2 for Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation

Groups^[1]	All groups
Method^[3]	Other [log-binomial regression model]
P-Value^[4]	0.659
Other^[5]	1.25
95% Confidence Interval	( 0.46 to 3.41 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The ratio of proportions was calculated by back-transforming the estimated treatment effect.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo for Days 1 - 30

3. Secondary Outcome Measure: Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation [ Time Frame: Day 1 of treatment phase up to 30 days post-randomisation. ]

Measure Type	Secondary
Measure Name	Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.
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.

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation [units: Participants]
Days 1 - 7	0	1
Days 1 - 14	1	1
Days 1 - 30	1	1

Statistical Analysis 1 for Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation

Groups^[1]	All groups
Method^[3]	Other [log-binomial regression model]
P-Value^[4]	0.944
Other^[5]	1.10
95% Confidence Interval	( 0.08 to 15.79 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The ratio of proportions was calculated by back-transforming the estimated treatment effect.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo for Days 1 - 14

Statistical Analysis 2 for Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation

Groups^[1]	All groups
Method^[3]	Other [log-binomial regression model]
P-Value^[4]	0.944
Other^[5]	1.10
95% Confidence Interval	( 0.08 to 15.79 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The ratio of proportions was calculated by back-transforming the estimated treatment effect.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo for Days 1 - 30

4. Secondary Outcome Measure: Time to first severe asthma exacerbation during 30 days following randomisation [ Time Frame: From Day 1 of treatment phase up to 30 days post-randomisation. ]

Measure Type	Secondary
Measure Name	Time to first severe asthma exacerbation during 30 days following randomisation
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.
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.

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Time to first severe asthma exacerbation during 30 days following randomisation [units: Days] Median (Full Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]

Statistical Analysis 1 for Time to first severe asthma exacerbation during 30 days following randomisation

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	0.634
Hazard Ratio (HR)^[5]	1.30
95% Confidence Interval	( 0.45 to 3.77 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of time to first severe exacerbation within 30 days of treatment start.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Hazard ratio was calculated adjusting for treatment group and region.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

5. Secondary Outcome Measure: Time to first moderate asthma exacerbation during 30 days following randomisation [ Time Frame: From Day 1 of treatment phase up to 30 days post-randomisation. ]

Measure Type	Secondary
Measure Name	Time to first moderate asthma exacerbation during 30 days following randomisation
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.
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.

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Time to first moderate asthma exacerbation during 30 days following randomisation [units: Days] Median (Full Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]

Statistical Analysis 1 for Time to first moderate asthma exacerbation during 30 days following randomisation

Groups^[1]	All groups
Method^[3]	Regression, Cox
P-Value^[4]	0.973
Hazard Ratio (HR)^[5]	1.05
95% Confidence Interval	( 0.07 to 16.78 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of time to first moderate exacerbation within 30 days of treatment start.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Hazard ratio was calculated adjusting for treatment group and region.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

6. Secondary Outcome Measure: Duration of moderate or severe exacerbations [ Time Frame: Day 1 of treatment phase up to 30 days post-randomisation. ]

Measure Type	Secondary
Measure Name	Duration of moderate or severe exacerbations
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.
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.

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	8	6
Duration of moderate or severe exacerbations [units: Days] Mean (Standard Deviation)	10 (7.7)	8 (4.5)

No statistical analysis provided for Duration of moderate or severe exacerbations

7. Secondary Outcome Measure: Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6) [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6)
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6) [units: Units on a Scale] Least Squares Mean (Standard Error)
ACQ-6 Total Score, Visit 4	0.02 (0.11)	-0.07 (0.12)
ACQ-6 Total Score, Visit 6	-0.15 (0.14)	-0.21 (0.14)
ACQ-6 Total Score, Visit 8	-0.42 (0.15)	-0.35 (0.15)
Q1: Woken by Asthma, Visit 4	0.09 (0.18)	-0.09 (0.18)
Q1: Woken by Asthma, Visit 6	0.15 (0.20)	-0.28 (0.21)
Q1: Woken by Asthma, Visit 8	-0.50 (0.18)	-0.32 (0.18)
Q2: Symptoms at Awakening, Visit 4	0.06 (0.18)	-0.17 (0.18)
Q2: Symptoms at Awakening, Visit 6	-0.40 (0.16)	-0.33 (0.17)
Q2: Symptoms at Awakening, Visit 8	-0.76 (0.19)	-0.47 (0.19)
Q3: Limited in Activities, Visit 4	0.04 (0.15)	0.06 (0.15)
Q3: Limited in Activities, Visit 6	-0.12 (0.17)	0.16 (0.18)
Q3: Limited in Activities, Visit 8	-0.43 (0.18)	-0.33 (0.18)
Q4: Shortness of Breath, Visit 4	-0.13 (0.15)	-0.11 (0.16)
Q4: Shortness of Breath, Visit 6	-0.34 (0.19)	-0.38 (0.21)
Q4: Shortness of Breath, Visit 8	-0.46 (0.18)	-0.37 (0.19)
Q5: Wheeze, Visit 4	0.13 (0.17)	0.08 (0.17)
Q5: Wheeze, Visit 6	-0.17 (0.17)	-0.17 (0.18)
Q5: Wheeze, Visit 8	-0.33 (0.21)	-0.42 (0.21)
Q6: Puffs of Short-Acting Bronchodilator; Visit 4	0.06 (0.13)	0.00 (0.14)
Q6: Puffs of Short-Acting Bronchodilator; Visit 6	0.07 (0.14)	-0.11 (0.15)
Q6: Puffs of Short-Acting Bronchodilator; Visit 8	0.04 (0.14)	-0.03 (0.14)

Statistical Analysis 1 for Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6)

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.495
Other^[5]	0.09
95% Confidence Interval	( -0.17 to 0.35 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of change from baseline in total score at Visit 4.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Change from baseline is analysed using an Analysis of Covariance (ANCOVA) model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo for change from baseline in total score at Visit 4.

Statistical Analysis 2 for Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6)

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.715
Other^[5]	0.06
95% Confidence Interval	( -0.26 to 0.38 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of change from baseline in total score at Visit 6.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 3 for Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6)

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.687
Other^[5]	-0.07
95% Confidence Interval	( -0.42 to 0.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of change from baseline in total score at Visit 8.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

8. Secondary Outcome Measure: AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days [units: Units on Scale] Least Squares Mean (Standard Error)
Total asthma score, Days 1-14	-0.20 (0.16)	-0.31 (0.16)
Total asthma score, Days 1-7	-0.11 (0.13)	-0.22 (0.13)
Total asthma score, Days 8-14	-0.40 (0.15)	-0.41 (0.16)
Total asthma score, Days 15-30	-0.77 (0.16)	-0.77 (0.16)
Daytime asthma score, Days 1-14	-0.22 (0.07)	-0.26 (0.07)
Daytime asthma score, Days 1-7	-0.17 (0.06)	-0.17 (0.06)
Daytime asthma score, Days 8-14	-0.23 (0.07)	-0.27 (0.07)
Daytime asthma score, Days 15-30	-0.44 (0.07)	-0.41 (0.07)
Night-time asthma score, Days 1-14	-0.17 (0.07)	-0.16 (0.08)
Night-time asthma score, Days 1-7	-0.10 (0.06)	-0.09 (0.07)
Night-time asthma score, Days 8-14	-0.20 (0.07)	-0.17 (0.08)
Night-time asthma score, Days 15-30	-0.44 (0.09)	-0.39 (0.09)

Statistical Analysis 1 for AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.516
Other^[5]	0.11
95% Confidence Interval	( -0.23 to 0.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline in total score over Days 1-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	AUC for change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 2 for AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.417
Other^[5]	0.11
95% Confidence Interval	( -0.16 to 0.37 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline in total score over Days 1-7.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	AUC for change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 3 for AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.954
Other^[5]	0.01
95% Confidence Interval	( -0.34 to 0.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline in total score over Days 8-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	AUC for change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 4 for AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.985
Other^[5]	0.00
95% Confidence Interval	( -0.35 to 0.35 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline in total score over Days 15-30.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	AUC for change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

9. Secondary Outcome Measure: Change in the proportion of night-time awakening using the ePRO questionnaire from baseline up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	Change in the proportion of night-time awakening using the ePRO questionnaire from baseline up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Change in the proportion of night-time awakening using the ePRO questionnaire from baseline up to 30 days [units: Percentage of 'yes' responses] Mean (Standard Deviation)
Days 2-15	22.3 (30.42)	24.8 (29.77)
Days 16-30	15.2 (26.79)	15.9 (26.34)

No statistical analysis provided for Change in the proportion of night-time awakening using the ePRO questionnaire from baseline up to 30 days

10. Secondary Outcome Measure: Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days [units: Units on Scale] Least Squares Mean (Standard Error)
Overall Score Visit 6	0.28 (0.13)	0.35 (0.14)
Overall Score Visit 8	0.43 (0.16)	0.53 (0.16)

Statistical Analysis 1 for Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.660
Other^[5]	-0.07
95% Confidence Interval	( -0.38 to 0.24 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of change from baseline in overall score at Visit 6.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 2 for Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.624
Other^[5]	-0.09
95% Confidence Interval	( -0.48 to 0.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of change from baseline in overall score at Visit 8.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

11. Secondary Outcome Measure: AUC for change in daytime and night-time reliever medication use from baseline up to 14 days [ Time Frame: From baseline up to Day 14 of treatment phase. ]

Measure Type	Secondary
Measure Name	AUC for change in daytime and night-time reliever medication use from baseline up to 14 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	52	48
AUC for change in daytime and night-time reliever medication use from baseline up to 14 days [units: Inhalations] Least Squares Mean (Standard Error)	-0.12 (0.46)	-0.67 (0.48)

Statistical Analysis 1 for AUC for change in daytime and night-time reliever medication use from baseline up to 14 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.309
Other^[5]	0.54
95% Confidence Interval	( -0.51 to 1.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	AUC for change from baseline is analysed using an ANCOVA model with treatment and region as factors and baseline value as covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

12. Secondary Outcome Measure: AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days [units: litres/minute (l/min)] Least Squares Mean (Standard Error)
Days 1-14	9.56 (14.02)	-7.42 (13.91)
Days 1-7	19.66 (9.66)	0.31 (9.11)
Days 8-14	7.03 (15.90)	-7.35 (15.80)
Days 15-30	32.75 (15.35)	13.49 (14.82)

Statistical Analysis 1 for AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.059
Other^[5]	16.98
95% Confidence Interval	( -0.63 to 34.60 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 2 for AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.010
Other^[5]	19.35
95% Confidence Interval	( 4.66 to 34.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-7.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 3 for AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.153
Other^[5]	14.38
95% Confidence Interval	( -5.44 to 34.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 8-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 4 for AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.096
Other^[5]	19.26
95% Confidence Interval	( -3.44 to 41.97 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 15-30.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

13. Secondary Outcome Measure: AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days [units: litres] Least Squares Mean (Standard Error)
Days 1-14	-0.00 (0.08)	-0.08 (0.08)
Days 1-7	0.10 (0.06)	0.02 (0.06)
Days 8-14	-0.03 (0.08)	-0.09 (0.08)
Days 15-30	0.15 (0.09)	0.04 (0.08)

Statistical Analysis 1 for AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.161
Other^[5]	0.07
95% Confidence Interval	( -0.03 to 0.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 2 for AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.087
Other^[5]	0.08
95% Confidence Interval	( -0.01 to 0.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-7.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 3 for AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.280
Other^[5]	0.06
95% Confidence Interval	( -0.05 to 0.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 8-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 4 for AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.086
Other^[5]	0.11
95% Confidence Interval	( -0.02 to 0.24 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 15-30.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

14. Secondary Outcome Measure: AUC for change in the evening PEF from baseline to up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	AUC for change in the evening PEF from baseline to up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
AUC for change in the evening PEF from baseline to up to 30 days [units: l/min] Least Squares Mean (Standard Error)
Days 1-14	10.96 (12.58)	-0.73 (11.88)
Days 1-7	8.78 (9.87)	-2.41 (9.30)
Days 8-14	8.49 (13.09)	-2.66 (12.55)
Days 15-30	11.88 (15.70)	-5.25 (15.13)

Statistical Analysis 1 for AUC for change in the evening PEF from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.211
Other^[5]	11.69
95% Confidence Interval	( -6.76 to 30.14 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 2 for AUC for change in the evening PEF from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.125
Other^[5]	11.19
95% Confidence Interval	( -3.18 to 25.56 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-7.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 3 for AUC for change in the evening PEF from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.277
Other^[5]	11.14
95% Confidence Interval	( -9.08 to 31.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 8-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 4 for AUC for change in the evening PEF from baseline to up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.161
Other^[5]	17.13
95% Confidence Interval	( -6.92 to 41.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 15-30.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

15. Secondary Outcome Measure: AUC for change in the evening FEV1 from baseline up to 30 days [ Time Frame: From baseline up to 30 days after start of treatment phase. ]

Measure Type	Secondary
Measure Name	AUC for change in the evening FEV1 from baseline up to 30 days
Measure Description	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.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

Description

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.

Placebo

Measured Values

	AZD9412	Placebo
Number of Participants Analyzed [units:participants]	61	60
AUC for change in the evening FEV1 from baseline up to 30 days [units: litres] Least Squares Mean (Standard Error)
Days 1-14	-0.01 (0.07)	-0.07 (0.07)
Days 1-7	0.01 (0.07)	-0.03 (0.07)
Days 8-14	-0.02 (0.07)	-0.08 (0.07)
Days 15-30	0.02 (0.08)	-0.08 (0.08)

Statistical Analysis 1 for AUC for change in the evening FEV1 from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.287
Other^[5]	0.06
95% Confidence Interval	( -0.05 to 0.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 2 for AUC for change in the evening FEV1 from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.457
Other^[5]	0.04
95% Confidence Interval	( -0.06 to 0.14 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 1-7.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 3 for AUC for change in the evening FEV1 from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.315
Other^[5]	0.05
95% Confidence Interval	( -0.05 to 0.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 8-14.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Statistical Analysis 4 for AUC for change in the evening FEV1 from baseline up to 30 days

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.134
Other^[5]	0.09
95% Confidence Interval	( -0.03 to 0.22 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of AUC for change from baseline over Days 15-30.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis uses an ANCOVA model with treatment, region, gender, and smoking status as factors, and baseline value and height as covariates.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	AZD9412 versus Placebo

Serious Adverse Events

Time Frame	Treatment emergent adverse events were collected from the first day of study treatment up to the last date of follow-up (approximately 30 days).
Additional Description	The safety analysis set consisted of all randomised patients who received at least 1 dose of investigational product and with post-dose data available.

Reporting Groups

Description

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 Million International Units (MIU) (24 micrograms [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 electronic Patient Reported Outcome (ePRO) device at home.

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.

Serious Adverse Events

AZD9412

Placebo

Total, serious adverse events

# participants affected / at risk

3/61 (4.92%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

3/61 (4.92%)

0/60 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version 19.1

Other Adverse Events

Time Frame	Treatment emergent adverse events were collected from the first day of study treatment up to the last date of follow-up (approximately 30 days).
Additional Description	The safety analysis set consisted of all randomised patients who received at least 1 dose of investigational product and with post-dose data available.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

Description

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 Million International Units (MIU) (24 micrograms [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 electronic Patient Reported Outcome (ePRO) device at home.

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.

Other Adverse Events

AZD9412

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

27/61 (44.26%)

20/60 (33.33%)

Blood and lymphatic system disorders

Eosinophilia¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Blood and lymphatic system disorders

Iron deficiency anaemia¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Blood and lymphatic system disorders

Lymphadenopathy¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Eye disorders

Blepharospasm¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Eye disorders

Periorbital oedema¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/61 (3.28%)

0/60 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/61 (3.28%)

0/60 (0.00%)

# events

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Gastrointestinal disorders

Mouth ulceration¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

Gastrointestinal disorders

Odynophagia¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

General disorders

Influenza like illness¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

General disorders

Injury associated with device¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

General disorders

Oedema peripheral¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Immune system disorders

Hypersensitivity¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

5/61 (8.20%)

1/60 (1.67%)

# events

Infections and infestations

Conjunctivitis bacterial¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Infections and infestations

Ear infection¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Infections and infestations

Laryngitis¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

2/61 (3.28%)

1/60 (1.67%)

# events

Infections and infestations

Rhinitis¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Infections and infestations

Tooth infection¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Injury, poisoning and procedural complications

Mouth injury¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Injury, poisoning and procedural complications

Muscle strain¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Investigations

Blood creatine phosphokinase increased¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Investigations

Blood pressure decreased¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Investigations

Glycosylated haemoglobin increased¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Investigations

Pulmonary function test decreased¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Metabolism and nutrition disorders

Diabetic ketoacidosis¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in jaw¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Tendonitis¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

2/61 (3.28%)

3/60 (5.00%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Nervous system disorders

Tremor¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Psychiatric disorders

Depressed mood¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Psychiatric disorders

Emotional distress¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Psychiatric disorders

Mood altered¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Psychiatric disorders

Panic attack¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

1/61 (1.64%)

4/60 (6.67%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchospasm¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/61 (1.64%)

2/60 (3.33%)

# events

Respiratory, thoracic and mediastinal disorders

Hiccups¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

2/61 (3.28%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

2/61 (3.28%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinitis allergic¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sinus pain¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Throat irritation¹,^†

# participants affected / at risk

1/61 (1.64%)

0/60 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Respiratory, thoracic and mediastinal disorders

Wheezing¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

Skin and subcutaneous tissue disorders

Eczema¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

1/61 (1.64%)

1/60 (1.67%)

# events

Skin and subcutaneous tissue disorders

Pruritus generalised¹,^†

# participants affected / at risk

0/61 (0.00%)

1/60 (1.67%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version 19.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated early due to the lower than expected rate of severe exacerbations in the study as a whole, and due to the observed lack of differential effect at interim analysis.

Results Point of Contact

Name/Title:	Medical Science Director
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Per Gustafson

AstraZeneca, R&D mölndal

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries