Efficacy and Safety Study of Mepolizumab Adjunctive Thera... | NCT01691521

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Mepolizumab IV	Experimental	Mepolizumab 75 mg will be administered intravenously approximately every 4 weeks with the last dose at week 32. Subjects in the Mepolizumab IV arm will receive mepolizumab 75 mg intravenously and placebo SC once every 4 weeks with the last dose at Week 28 (total of 8 doses)	Drug: Mepolizumab IV Drug: SC Placebo
Mepolizumab SC	Experimental	Subjects in the Mepolizumab SC arm will receive mepolizumab 100 mg SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)	Drug: Mepolizumab SC Drug: IV Placebo
Placebo	Placebo Comparator	Subjects in the Placebo arm will receive matching placebo SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)	Drug: IV Placebo Drug: SC Placebo

Name	Type	Description	Arm Group Labels	Other Names
Mepolizumab IV	Drug	Mepolizumab 75 mg IV will be administered every 4 weeks with the last dose at Week 28	Mepolizumab IV

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Clinically Significant Exacerbations of Asthma Per Year	Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.	From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose

Secondary Outcomes

Measure	Description	Time Frame
Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year	Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Able to give written informed consent prior to participation in the study
At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS)
Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months
Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma
At Visit 1, a pre-bronchodilator FEV1 <80% (for subjects >= 18 years of age), a pre-bronchodilator FEV1 <90% or FEV1:FVC ratio <0.8 (for subjects 12-17 years of age).
Previously confirmed history of two or more exacerbations requiring treatment with systemic CS
Male or Eligible Female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control)
French subjects will be included only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

Current smokers or former smokers with a smoking history of >=10 pack years
Presence of a known pre-existing, clinically important lung condition other than asthma
A current malignancy or previous history of malignancy in less than 12 months
Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities
Known, pre-existing severe or clinically significant cardiovascular disease
known, pre-existing other concurrent clinically significant medical conditions that are uncontrolled with standard treatment
Subjects with any eosinophilic diseases
QTc(F) ≥450msec or QTc(F) ≥480 msec
A history of alcohol/substance abuse
Subject with known immunodeficiency
Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1
Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer
Subjects with allergy/intolerance to a monoclonal antibody or biologic.
Subjects who are pregnant or breastfeeding
Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations
Previously participated in any study with mepolizumab and received investigational product (including placebo)

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Birmingham	Alabama	35294	United States
GSK Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37131185	Derived	Chen W, Reddel HK, FitzGerald JM, Beasley R, Janson C, Sadatsafavi M. Can we predict who will benefit most from biologics in severe asthma? A post-hoc analysis of two phase 3 trials. Respir Res. 2023 May 2;24(1):120. doi: 10.1186/s12931-023-02409-2.
34158028	Derived	Lemiere C, Taille C, Lee JK, Smith SG, Mallett S, Albers FC, Bradford ES, Yancey SW, Liu MC. Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials. Respir Res. 2021 Jun 22;22(1):184. doi: 10.1186/s12931-021-01767-z.

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
115588	Informed Consent Form	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo intravenously (IV) plus placebo subcutaneously (SC) every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
BG001	Mepolizumab 75 mg IV	Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
BG002	Mepolizumab 100 mg SC	Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
BG003	Total	Total of all reporting groups

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 Clinically Significant Exacerbations of Asthma Per Year

Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.

Modified Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of trial medication. 'Modified' implies that, in cases where there is is a discrepancy between randomized and actual treatment the analysis used the actual treatment received by the participant rather than the randomized treatment.

Posted

Number

Number of exacerbations per year

From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose

ID	Title	Description
OG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
OG001	Mepolizumab 75 mg IV	Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
OG002	Mepolizumab 100 mg SC	Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.

Units	Counts
Participants	OG000191 OG001191 OG002194

Title

Denominators

Categories

Title	Measurements
	OG0001.74 OG0010.93 OG0020.83

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		<0.001	Hochberg procedure with a gamma parameter of 1 used for multiplicity adjustment.	Rate Ratio	0.53			2-Sided	95	0.40	0.72			Number of exacerbations per year in the mepolizumab 75mg IV arm divided by the number of exacerbations per year in the placebo arm.		Superiority or Other

Secondary

Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year

ITT Population

Posted

Number

Number of exacerbations per year

From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose

ID	Title	Description
OG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.

Secondary

Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an ICU) Per Year

Clinically significant exacerbations of asthma is defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.

ITT Population

Posted

Number

Number of exacerbations per year

From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose

ID	Title	Description
OG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
OG001

Secondary

Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 32

FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using mixed model repeated measures with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.

ITT Population. Only participants with a Baseline FEV1 available and at least one post-Baseline FEV1 measurement were analyzed.

Posted

Least Squares Mean

Standard Error

Milliliters (mL)

Baseline, Week 32

ID	Title	Description
OG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
OG001	Mepolizumab 75 mg IV	Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.

Secondary

Mean Change From Baseline in the St. George's Respiratory Questionnaire Total Score at Week 32

The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. The lowest possible value is zero and the highest possible value is 100. The higher values correspond to greater impairment in quality of life. The questionnaire was administered at Baseline (Visit 2) and at the Exit Visit (approximately 4 weeks after the last dose of study treatment). The change from baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using analysis of covariance with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, and treatment.

ITT Population. Note that only participants with a Baseline and Week 32 assessment were included in the analysis.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline, Week 32

ID	Title	Description
OG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	27	191	143	191
EG001	Mepolizumab 75 mg IV	Participants received mepolizumab 75 mg IV plus placebo SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	14	191	142	191
EG002	Mepolizumab 100 mg SC	Participants received placebo IV plus mepolizumab 100 mg SC every 4 weeks (for a total of 8 doses), with the last dose at Week 28. The SC dose and the IV dose were administered into separate arms. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study	16	194	132	194

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00014 affected191 at risk EG0019 affected191 at risk EG0025 affected194 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0022 affected194 at risk
Clostridium difficile infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Croup infectious	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Postoperative wound infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Urosepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Vulval abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Fractured coccyx	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Heat stroke	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Inflammation of wound	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Calculus urethral	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Nephrogenic diabetes insipidus	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Renal colic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Gastrointestinal motility disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Oesophageal spasm	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Epilepsy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Sciatica	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0011 affected191 at risk EG0020 affected194 at risk
Dyshidrotic eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Atrial flutter	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Intracranial lipoma	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk
Gallbladder disorder	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected191 at risk EG0010 affected191 at risk EG0021 affected194 at risk
Major depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0010 affected191 at risk EG0020 affected194 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00046 affected191 at risk EG00145 affected191 at risk EG00233 affected194 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00033 affected191 at risk EG00146 affected191 at risk EG00239 affected194 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00027 affected191 at risk EG00122 affected191 at risk EG00224 affected194 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG00018 affected191 at risk EG00111 affected191 at risk EG00218 affected194 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG00016 affected191 at risk EG00114 affected191 at risk EG0029 affected194 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00016 affected191 at risk EG00111 affected191 at risk EG0029 affected194 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00015 affected191 at risk EG00112 affected191 at risk EG0027 affected194 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0007 affected191 at risk EG00111 affected191 at risk EG00214 affected194 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0009 affected191 at risk EG00110 affected191 at risk EG00211 affected194 at risk
Injection site reaction	General disorders	MedDRA	Systematic Assessment	EG0006 affected191 at risk EG0015 affected191 at risk EG00217 affected194 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0009 affected191 at risk EG0018 affected191 at risk EG0025 affected194 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0009 affected191 at risk EG0018 affected191 at risk EG0025 affected194 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected191 at risk EG00110 affected191 at risk EG0025 affected194 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00010 affected191 at risk EG0013 affected191 at risk EG0028 affected194 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected191 at risk EG0014 affected191 at risk EG0025 affected194 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected191 at risk EG00110 affected191 at risk EG0023 affected194 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected191 at risk EG0017 affected191 at risk EG0027 affected194 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 affected191 at risk EG0014 affected191 at risk EG0026 affected194 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected191 at risk EG0014 affected191 at risk EG0025 affected194 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected191 at risk EG0015 affected191 at risk EG0028 affected194 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected191 at risk EG0015 affected191 at risk EG0026 affected194 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected191 at risk EG0012 affected191 at risk EG0029 affected194 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0004 affected191 at risk EG0016 affected191 at risk EG0023 affected194 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected191 at risk EG0015 affected191 at risk EG0027 affected194 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected191 at risk EG0012 affected191 at risk EG0027 affected194 at risk
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0006 affected191 at risk EG0011 affected191 at risk EG0025 affected194 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0006 affected191 at risk EG0013 affected191 at risk EG0023 affected194 at risk
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected191 at risk EG0017 affected191 at risk EG0021 affected194 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected191 at risk EG0016 affected191 at risk EG0022 affected194 at risk
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0003 affected191 at risk EG0016 affected191 at risk EG0022 affected194 at risk
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected191 at risk EG0010 affected191 at risk EG0026 affected194 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