A Clinical Study to Evaluate Symbicort Turbuhaler Used 'a... | NCT02224157

NCT02224157

ID	Type	Description	Link
2013-004473-28	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Symbicort "as needed"+placebo Pulmicort bid	Experimental	Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid	Drug: budesonide/formoterol 'as needed' + budesonide placebo bid
Pulmicort bid + terbutaline "as needed"	Active Comparator	Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'	Drug: budesonode bid + terbutaline 'as needed'

Interventions

Name	Type	Description	Arm Group Labels	Other Names
budesonide/formoterol 'as needed' + budesonide placebo bid	Drug	Symbicort (budesonide/ formoterol) 160/4.5 μg powder for inhalation 'as needed' plus Pulmicort placebo 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis	Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation	up to 52 weeks
Annual Severe Asthma Exacerbation Rate - Superiority Analysis	Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation	up to 52 weeks

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Experiencing at Least One Severe Asthma Exacerbation	A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.	Day 1 up to 52 weeks

Eligibility Module

Name	Affiliation	Role
Carin Jorup, MD	AstraZeneca Research & Development	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Sydney		2010	Australia
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33548020	Derived	FitzGerald JM, O'Byrne PM, Bateman ED, Barnes PJ, Zheng J, Ivanov S, Lamarca R, Larsdotter U, Emerath U, Jansen G, Puu M, Alagappan VKT, Surmont F, Reddel HK. Safety of As-Needed Budesonide-Formoterol in Mild Asthma: Data from the Two Phase III SYGMA Studies. Drug Saf. 2021 Apr;44(4):467-478. doi: 10.1007/s40264-020-01041-z. Epub 2021 Feb 6.
29768147

Label	URL
D589SC00003-revised-csp-edition-4\_12Oct2016\_Redacted\_pdfa	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
FG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Sep 6, 2017	Apr 10, 2019

Arm/Group Information

ID	Title	Description
BG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
BG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00041.3± 16.8 BG00140.7± 17.1 BG00241.0± 17.0

Sex/Gender, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001308 BG0011289 BG002

Race/Ethnicity, Customized

Full Analysis Set

Number

Participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG00036 BG00132 BG002

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

Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis

Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

exacerbations per participant year

up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG0002089 OG0012087

Title

Denominators

Categories

Title	Measurements
	OG0000.11(0.10 to 0.13) OG0010.12(0.10 to 0.14)

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		Negative binomial model	Adjusted for randomised treatment, pre-study treatment and region. Logarithm of follow-up time is used as an offset variable.			Rate ratio	0.97			1-Sided	95		1.16			A rate ratio less than 1 indicates a lower rate of exacerbations in the Symbicort 'as needed' treatment group.		Non-Inferiority	Non-inferiority analysis based on CI instead of p-value, hence no p-value calculated for this analysis. Upper limit of the 1-sided 95% confidence limit <1.2 indicates Symbicort 'as needed' is non-inferior to Pulmicort bid

Secondary

Number of Participants Experiencing at Least One Severe Asthma Exacerbation

A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.

Full analysis set

Posted

Number

Participants

Day 1 up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Secondary

Average Change From Baseline in Pre-bronchodilator FEV1

The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

Study weeks 0,17, 34, 52

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Secondary

Number of Participants With Study Specific Asthma Related Discontinuation

The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.

Full analysis set

Posted

Number

Participants

Day 1 up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Secondary

Average Change From Baseline in 'as Needed' Use

'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.

Full analysis set.

Posted

Least Squares Mean

95% Confidence Interval

Number of inhalations per day

Week 0 up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Percent of 'as Needed' Free Days

'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

Percentage of 'as needed' free days

Week 0 up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Secondary

Percentage of Controller Use Days

ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

Percentage of days

Week 0 up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Secondary

Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score

ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.

Full analysis set.

Posted

Least Squares Mean

95% Confidence Interval

Score

Study weeks 0, 17, 34, 52

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants

Secondary

Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score

AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.

Full Analysis Set.

Posted

Least Squares Mean

95% Confidence Interval

AQLQ(S) overall score

Study weeks 0,17, 34, 52

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants

Primary

Annual Severe Asthma Exacerbation Rate - Superiority Analysis

Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

exacerbations per participant year

up to 52 weeks

ID	Title	Description
OG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)
OG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Bid + Symbicort 'as Needed' (Experimental)	Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)	1	2,089	66	2,089	491	2,089
EG001	Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)	Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'	1	2,087	73	2,087	519	2,087

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute sinusitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Appendicitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0002 events2 affected2,089 at risk EG0011 events1 affected2,087 at risk
Chronic sinusitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0002 events2 affected2,089 at risk EG0010 events0 affected2,087 at risk
Cystitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Dengue fever	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Gastroenteritis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Influenza	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Pharyngitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Pneumonia	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0002 events2 affected2,089 at risk EG0011 events1 affected2,087 at risk
Pneumonia bacterial	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0012 events2 affected2,087 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Postoperative wound infection	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Pyelonephritis acute	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Sinusitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Urinary tract infection	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Vestibular neuronitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Benign neoplasm of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Breast cancer female	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Sebaceous adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0012 events2 affected2,087 at risk
Anaphylactic reaction	Immune system disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Drug hypersensitivity	Immune system disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Depression	Psychiatric disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Epilepsy	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Headache	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG0002 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Radiculopathy	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Cataract	Eye disorders	MedDRA version 20.0	Systematic Assessment	EG0002 events2 affected2,089 at risk EG0010 events0 affected2,087 at risk
Visual impairment	Eye disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Deafness neurosensory	Ear and labyrinth disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Adams-Stokes syndrome	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Angina unstable	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Atrial fibrilation	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0012 events2 affected2,087 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Cardiomyopathy	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Degenerative aortic valve disease	Cardiac disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Hypertension	Vascular disorders	MedDRA version 20.0	Systematic Assessment	EG0002 events2 affected2,089 at risk EG0010 events0 affected2,087 at risk
Hypertensive crisis	Vascular disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Thrombophlebitis	Vascular disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG00020 events17 affected2,089 at risk EG00117 events17 affected2,087 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Nasal turbinate hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG0002 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Vocal cord polyp	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Biliary colic	Hepatobiliary disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0012 events1 affected2,087 at risk
Hydrocholecystitis	Hepatobiliary disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Sphincter of Oddi dysfunction	Hepatobiliary disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Hirsutism	Skin and subcutaneous tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Intervertebral disc protusion	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0012 events2 affected2,087 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0012 events2 affected2,087 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Incarcerated umbilical hernia	Gastrointestinal disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Cystistis interstitial	Renal and urinary disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Ureteric stenosis	Renal and urinary disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Adenomyosis	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Breast mass	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Endometriosis	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Rectocele	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Abdominal injury	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0012 events2 affected2,087 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Ligament injury	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Lumbosacral plexus injury	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Post procedural complication	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Post procedural swelling	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0011 events1 affected2,087 at risk
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0000 events0 affected2,089 at risk EG0011 events1 affected2,087 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA version 20.0	Systematic Assessment	EG0001 events1 affected2,089 at risk EG0010 events0 affected2,087 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Viral upper respiratory tract infection	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG000188 events155 affected2,089 at risk EG001206 events168 affected2,087 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG00095 events81 affected2,089 at risk EG00196 events84 affected2,087 at risk
Headache	Nervous system disorders	MedDRA version 20.0	Systematic Assessment	EG00069 events51 affected2,089 at risk EG00168 events50 affected2,087 at risk
Bronchitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG00070 events64 affected2,089 at risk EG00183 events78 affected2,087 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG00090 events81 affected2,089 at risk EG001112 events89 affected2,087 at risk
Pharyngitis	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG00055 events51 affected2,089 at risk EG00174 events62 affected2,087 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA version 20.0	Systematic Assessment	EG00056 events51 affected2,089 at risk EG00146 events44 affected2,087 at risk
Influenza	Infections and infestations	MedDRA version 20.0	Systematic Assessment	EG00034 events33 affected2,089 at risk EG00146 events42 affected2,087 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	Term
D011282	Pregnenediones
D011283	Pregnenes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds