A 6 Month Safety Study Comparing Symbicort With Inhaled C... | NCT01444430

ID	Type	Description	Link
2011-002790-28	EudraCT Number

Label	Type	Description	Intervention Names
1	Experimental	Symbicort	Drug: Symbicort pMDI
2	Active Comparator	budesonide	Drug: budesonide pMDI

Name	Type	Description	Arm Group Labels	Other Names
Symbicort pMDI	Drug	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening), for oral inhalation.

Measure	Description	Time Frame
Number of Participants Experiencing an Event in the Composite Endpoint (Asthma-related Death, Asthma-related Intubation or Asthma-related Hospitalization)	Number of participants experiencing an event in the composite endpoint (asthma-related death, asthma-related intubation or asthma-related hospitalization), using events adjudicated and confirmed by the Joint Adjudication Committee. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.	Up to 27 weeks
Number of Participants Experiencing an Event Included in the Definition of Asthma Exacerbation	Number of participants experiencing an event included in the definition of asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.	Up to 26 weeks

Measure	Description	Time Frame
Percent of Days With no Asthma Symptoms	Percent of days with no asthma symptoms during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.	Daily up to 26 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of signed informed consent/ paediatric assent (if applicable) prior to any study specific procedures including medication withdrawal
Male or Female, ≥12 years of age
Documented clinical diagnosis of asthma for at least 1 year prior to Visit 2
Patient must have history of at least 1 asthma exacerbation including one of the following:
- requiring treatment with systemic corticosteroids
- an asthma-related hospitalization between 4 weeks and 12 months prior to randomization
Current Asthma Therapy: Patients must be appropriately using one of the treatments for asthma listed in the protocol combined with achieving certain results when recording an Asthma Control Questionnaire

Exclusion Criteria:

Patient has a history of life-threatening asthma. Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea requiring non-invasive ventilatory support.
Patient has required treatment with systemic corticosteroids (tablets, suspensions or injectable) for any reason within 4 weeks prior to Visit 2
Patient has an ongoing exacerbation, defined as a worsening of asthma that requires treatment with systemic corticosteroids (tablets, suspension, or injectable)
An asthma exacerbation within 4 weeks of randomization or more than 4 separate exacerbations in the 12 months preceding randomization or more than 2 hospitalizations for treatment of asthma in the 12 months preceding randomization
Patient has a respiratory infection or other viral/bacterial illness, or is recovering from such an illness at the time of Visit 2 that, in the investigator's opinion, will interfere with the patient's lung function
Patient must not meet unstable asthma severity criteria as listed in the protocol
Peak expiratory flow must not be below 50% o predicted normal
Pregnancy, breast-feeding or planned pregnancy during the study

Name	Affiliation	Role
Carin Jorup	AstraZeneca Pepparedsleden 1, 431 83 Mölndal	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama		United States
Research Site

PubMed Identifier	Type	Citation	Retractions
27579635	Derived	Peters SP, Bleecker ER, Canonica GW, Park YB, Ramirez R, Hollis S, Fjallbrant H, Jorup C, Martin UJ. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. N Engl J Med. 2016 Sep 1;375(9):850-60. doi: 10.1056/NEJMoa1511190.

Label	URL
D5896C00027\_Protocol\_redacted.pdf	View source

ID	Title	Description
FG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Experiencing an Event in the Composite Endpoint (Asthma-related Death, Asthma-related Intubation or Asthma-related Hospitalization)

Number of participants experiencing an event in the composite endpoint (asthma-related death, asthma-related intubation or asthma-related hospitalization), using events adjudicated and confirmed by the Joint Adjudication Committee. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.

Full analysis set (FAS) population comprised of all patients randomized to study drug.

Posted

Number

Participants

Up to 27 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Units	Counts
Participants	OG0005846 OG0015847

Title

Denominators

Categories

Title	Measurements
	OG00043 OG00140

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox				Hazard Ratio (HR)	1.073			2-Sided	95	0.698	1.650				Yes	Non-Inferiority or Equivalence	The upper limit of the 95% CI of the hazard ratio will be used to assess statistical non-inferiority (non-inferiority margin=2).

Primary

Number of Participants Experiencing an Event Included in the Definition of Asthma Exacerbation

Number of participants experiencing an event included in the definition of asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.

The On treatment Analysis set comprised of all randomized patients and included data that corresponded to each patient's period of exposure to study drug plus 7 days after the last date of study drug treatment.

Posted

Number

Participants

Up to 26 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Secondary

Percent of Days With no Asthma Symptoms

Percent of days with no asthma symptoms during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.

Full analysis set (FAS) population comprised of all patients randomized to study drug and had at least one entry of diary data after randomization.

Posted

Least Squares Mean

Standard Error

Percentage of days

Daily up to 26 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Units	Counts

Secondary

Percent of Days With Activity Limitation Due to Asthma

Percent of days with activity limitation due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.

Full analysis set (FAS) population comprised of all patients randomized to study drug. The analysis set comprises of all patients with at least one day with asthma symptoms, i.e. the denominator is the number of days with asthma symptoms.

Posted

Least Squares Mean

Standard Error

Percentage of days

Daily up to 26 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Secondary

Mean Number of Puffs of Rescue Medication Per 24 Hours

Mean number of puffs of rescue medication per day (24 hours) during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.

Full analysis set (FAS) population comprised of all patients randomized to study drug and had at least one entry of diary data after randomization.

Posted

Least Squares Mean

Standard Error

Inhalations/day

Daily up to 26 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Units	Counts

Secondary

Asthma Control Questionnaire (ACQ6)

The outcome variable for ACQ6 was the difference between the average of values recorded during the treatment period (day 28, day 84 and day 182) and the baseline measure. Analysis of covariance (ANCOVA) model, including the fixed factors of treatment and strata by incoming control/asthma treatment and baseline ACQ6 as covariate was used to compare Symbicort and budesonide.

The asthma control questionnaire, ACQ6, consists of six questions; all assessed on a 7-point scale from 0 to 6, where 0 represents good control and 6 represents poor control. The overall score is the mean of the responses to each of the six questions.

Full analysis set (FAS) population comprised of all patients randomized to study drug with at least one post-baseline ACQ6 score.

Posted

Least Squares Mean

Standard Error

ACQ6 overall score change from baseline

baseline, day 28, day 84, day 182

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Secondary

Percent of Nights With Awakening(s) Due to Asthma

Percent of nights with awakening(s) due to asthma during the randomized treatment period. Analysis of variance (ANOVA) model including the fixed factors of treatment and strata by incoming control/asthma treatment was used to compare Symbicort and budesonide.

Full analysis set (FAS) population comprised of all patients randomized to study drug and had at least one entry of diary data after randomization.

Posted

Least Squares Mean

Standard Error

Percentage of nights

Daily up to 26 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Units	Counts

Secondary

Number of Participants Experiencing Discontinuation of Investigational Product Due to a Protocol Defined Asthma Exacerbation

Number of participants experiencing discontinuation of investigational product due to a protocol defined asthma exacerbation. An asthma exacerbation was defined as a deterioration of asthma requiring systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency room visit due to asthma that required systemic corticosteroids. Cox proportional hazards model with terms for randomized treatment and strata for incoming control/asthma treatment was used to compare Symbicort and budesonide. Hazard ratios and 95% confidence intervals were estimated.

Posted

Number

Participants

Up to 26 weeks

ID	Title	Description
OG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
OG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy mediastinal	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Angina pectoris	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected5,846 at risk EG0011 events1 affected5,847 at risk
Angina unstable	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0011 events1 affected5,847 at risk
Arrhythmia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0013 events3 affected5,847 at risk
Atrial flutter	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Coronary artery disease	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Coronary artery insufficiency	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hypertensive heart disease	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Mitral valve stenosis	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Myocarditis	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Tachycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0012 events2 affected5,847 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Abdominal hernia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0012 events2 affected5,847 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0013 events3 affected5,847 at risk
Colitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Erosive oesophagitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Gastric ulcer perforation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0012 events2 affected5,847 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Intussusception	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Oesophagitis haemorrhagic	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Chest pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Death	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Device dislocation	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Influenza like illness	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Non-cardiac chest pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0012 events2 affected5,847 at risk
Biliary colic	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Biliary dyskinesia	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Allergic granulomatous angiitis	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Anaphylactic shock	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Hypersensitivity	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Abdominal abscess	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Acute sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Appendicitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Bronchitis bacterial	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cellulitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Cystitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Diarrhoea infectious	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Dysentery	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Haemophilus infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Herpes zoster	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Influenza	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0012 events2 affected5,847 at risk
Lower respiratory tract infection bacterial	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Malaria	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Mycoplasma infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Osteomyelitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Pharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00012 events12 affected5,846 at risk EG0016 events6 affected5,847 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0013 events3 affected5,847 at risk
Postoperative wound infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Rhinitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Sepsis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0011 events1 affected5,847 at risk
Tuberculous pleurisy	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0012 events2 affected5,847 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Burns first degree	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Burns second degree	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Electric shock	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Wound	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Blood pressure increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Heart rate irregular	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0010 events0 affected5,847 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hyperosmolar hyperglycaemic state	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0011 events1 affected5,847 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0013 events3 affected5,847 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0011 events1 affected5,847 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0012 events2 affected5,847 at risk
Astrocytoma malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Breast cancer female	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Colorectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Ovarian germ cell teratoma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cerebral haematoma	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Cerebral infarction	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0014 events3 affected5,847 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Monoparesis	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Seizure	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Syncope	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hyperemesis gravidarum	Pregnancy, puerperium and perinatal conditions	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Aggression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Bipolar I disorder	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Completed suicide	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Depression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Stress	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Suicide attempt	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Nephritis	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Pelvi-ureteric obstruction	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Urinary tract infection	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Haemorrhagic ovarian cyst	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Menometrorrhagia	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Pelvic prolapse	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG00038 events35 affected5,846 at risk EG00139 events36 affected5,847 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0012 events2 affected5,847 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Status asthmaticus	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk
Vocal cord disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Haematoma	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected5,846 at risk EG0011 events1 affected5,847 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected5,846 at risk EG0010 events0 affected5,847 at risk

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description
BG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).
BG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Symbicort	Patients were randomized to Symbicort and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): Symbicort pMDI 80/4.5 μg x 2 actuations bid (morning and evening) or Symbicort pMDI 160/4.5 μg x 2 actuations bid (morning and evening).			125	5,846	0	5,846
EG001	Budesonide	Patients were randomized to budesonide and assigned to one of the following treatments (based upon ACQ at baseline and prior asthma therapy): budesonide pMDI 80 μg x 2 actuations bid (morning and evening) or budesonide pMDI 160 μg x 2 actuations bid (morning and evening).			123	5,847	0	5,847