A Study to Test if the Vaccine is Working Well in Chronic... | NCT03281876

ID	Type	Description	Link
2017-000880-34	EudraCT Number

Description Module

Detailed Description

The purpose of this Phase IIB proof-of-concept (POC) study in moderate to very severe COPD patients (i.e. GOLD grade 2, 3 and 4) aged 40 to 80 years with a history of moderate or severe acute exacerbations of COPD (AECOPD) in the previous 12 months is to evaluate whether the NTHi-Mcat vaccine can reduce the frequency of AECOPD in this population and to assess the vaccine's safety, reactogenicity and immunogenicity.

Several formulations of a vaccine containing the NTHi antigens (low or high formulation) either non-adjuvanted or combined with different adjuvants (aluminium [Al], adjuvant system) were already evaluated in two previous Phase I clinical trials (NTHI-002 in healthy adults aged 18 - 40 years and NTHI-003 in current and former healthy smokers of 50-70 years old). The investigational vaccines were well-tolerated, with an acceptable safety and reactogenicity profile. These studies allowed the dose selection of the NTHi antigens (low formulation) and the adjuvant system currently evaluated for the first time in moderate and severe COPD patients aged 45 - 81 years in the Phase II study NTHI-004.

The safety, reactogenicity and immunogenicity of different formulations of the NTHi-Mcat investigational vaccine have been evaluated in the Phase I study in healthy adults aged 19 - 40 years and in current and former smokers aged 50 - 70 years (study NTHI MCAT-001). Based on results obtained up to 30 days post-Dose 2 from this study, the adjuvanted formulation containing NTHi proteins PD and PE-PilA and of UspA2 has been selected for evaluation in the current NTHI MCAT-002 study. Placebo will be used as a control. The NTHi-Mcat investigational vaccine and placebo will be given on top of standard of care to subjects in the respective study groups.

In the current study, moderate, severe and very severe COPD patients (i.e. GOLD grade 2, 3 and 4) with a history of AECOPD will receive 2 doses of the NTHi-Mcat investigational vaccine or placebo intramuscularly (IM) according to a 0, 2 month vaccination schedule, in addition to standard care.

Scheduled study visits, during which the effect of immunisation against NTHi and Mcat will be evaluated, will take place at pre-defined timepoints.

In addition to the scheduled study visits, ad hoc AECOPD-driven study visit(s) and/ or phone contact(s) will take place for each AECOPD occurring from first vaccination up to study conclusion:

An AECOPD visit will be scheduled as soon as possible after the onset of the AECOPD symptoms (maximum 96 hours after the onset of the symptoms).
Follow-up visit(s) and/or phone call(s) will take place to determine the end of the AECOPD.

Rationale for the protocol amendment:

CD8+ T cell component was removed from the secondary endpoint, but kept in the exploratory/tertiary endpoint. Previous clinical studies have shown that the investigational NTHi and NTHi-Mcat vaccines do not induce CD8+ T cell responses. This was observed in all studies performed with the NTHi vaccine and seen in the interim analysis of NTHi Mcat-001 study.
An exclusion criterion was updated to clarify that only subjects with clinically significant respiratory diseases other than COPD (e.g. clinically significant lung fibrosis, clinically significant pulmonary embolism) need to be excluded from study participation.
The polymerase chain reaction (PCR) assay for sputum samples was not designed to discriminate amongst Haemophilus influenzae (Hi) serotypes. Results from AERIS epidemiological study [Wilkinson, 2017] showed that more than 99% of these bacteria would be Non-Typeable Haemophilus influenzae (NTHi). Therefore, the protocol was updated to clarify that the presence of Hi bacteria in sputum during exacerbation will be used to determine AECOPD associated to NTHi.
The list of potential immune mediated diseases was updated (effective June 30th 2017).
The 87% confidence interval (CI) was removed from all secondary analyses. This confidence interval will only be maintained for the primary analysis because the 95% CIs are underpowered for this study. All other sensitivity analyses on different cohorts will be described using 95% CIs. As the primary objective will have both 87% and 95%, the sensitivity analyses can be interpreted with 95% CIs.
A Full-Analysis Set (FAS) that corresponds to an intent-to-treat analysis was added. The FAS will include all randomized subjects who will receive at least 1 vaccine administration and, as per intention-to-treat principle, a subject in the FAS will be analysed "as randomized" (i.e. according to the vaccine a subject was planned to receive irrespectively of his/her real exposure).
Cut-off values for anti-PE, anti-PilA and anti-UspA2 antibody ELISAs were updated following the re-set up of the assays.
Additional minor updates were based on the scientific and operational experience gained from current COPD studies.

Label	Type	Description	Intervention Names
GSK3277511A Group	Experimental	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2) at Day 1 and Day 61.	Biological: NTHi Mcat investigational vaccine (GSK3277511A)
CONTROL Group	Placebo Comparator	Healthy males and females, 40 to 80 years of age, who received two doses of placebo vaccine at Day 1 and Day 61.	Biological: Placebo

Name	Type	Description	Arm Group Labels	Other Names
NTHi Mcat investigational vaccine (GSK3277511A)	Biological	Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.	GSK3277511A Group

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year	Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.	From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year	Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.	From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects Reported With Each Solicited Local Adverse Event (AE)	Assessed solicited local symptoms were pain, redness and swelling	During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61
Number of Subjects Reported With Each Solicited General AE

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
Written informed consent obtained from the subject prior to performing any study specific procedure.
A male or female between, and including, 40 and 80 years of age at the time of the first vaccination.
Confirmed diagnosis of COPD with forced expiratory volume in 1 second (FEV1) over forced vital capacity (FVC) ratio (FEV1/FVC) < 0.7, AND FEV1 < 80% predicted (GOLD 2, 3 and 4).
Current or former smoker with a cigarette smoking history of ≥ 10 pack-years.
Stable COPD patient* with documented history** of at least 1 moderate or severe AECOPD within the 12 months before Screening.
- Patient for whom the last episode of AECOPD is resolved for at least 30 days at the time of first vaccination.
  - A documented history of a COPD exacerbation is a medical record of worsening COPD symptoms that required systemic/oral corticosteroids and/or antibiotics (for a moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence. Subject verbal reports are not acceptable.
Capable of complying with the daily electronic Diary Card completion throughout the study period, according to investigator's judgement at Visit 1.
Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
Female subjects of childbearing potential may be enrolled in the study, if the subject:

has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period.
Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine, with the exception of any influenza or pneumococcal vaccine which may be administered ≥15 days preceding or following any study vaccine dose.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose (e.g. methotrexate).
Administration of systemic corticosteroids within the 30 days before first vaccination.

Subjects who received systemic corticosteroids within this period may be enrolled at a later date if enrolment is still open.

Inhaled and topical steroids are allowed.

• Administration of systemic antibiotics within the 30 days before first vaccination.

Subjects who received systemic antibiotics within this period may be enrolled at a later date if enrolment is still open.

Chronic use of antibiotics for prevention of AECOPD (e.g. azithromycin).
Acute disease and/or fever at the time of first vaccination. Fever is defined as temperature ≥37.5°C. The preferred location for measuring temperature in this study will be the oral cavity or the axilla.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.

Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy >3L/min (Oxygen use ≤3L/min flow is not exclusionary).
Planned lung transplantation.
Lung resection: Subjects with planned lung volume reduction surgery during the study or within the 12 months prior to first vaccination.
Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD.
Diagnosed with a respiratory disorder other than COPD at time of enrolment (such as sarcoidosis, active tuberculosis, clinically significant bronchiectasis, clinically significant lung fibrosis, clinically significant pulmonary embolism, clinically significant pneumothorax, current diagnosis of asthma in the opinion of the investigator), or chest X-ray/ CT scan revealing evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Subjects with allergic rhinitis do not need to be excluded and may be enrolled at the discretion of the investigator.
History of immune-mediated disease other than COPD. If the subject has any condition on the non-exhaustive list of potential immune-mediated diseases defined in the protocol, they must be excluded unless the aetiology is clearly documented to be non-immune mediated.
Previous vaccination with any vaccine containing NTHi and/ or Mcat antigens.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines and/ or the bronchodilator used for spirometry assessment during the study.
Contraindication for spirometry testing.
Unstable or life threatening cardiac disease: subjects with any of the following at Screening (Visit 1) would be excluded:

Myocardial infarction or unstable angina in the last 6 months. Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months NYHA Class IV Heart failure

Malignancies within the previous 5 years or lymphoproliferative disorder.
Any known disease or condition likely to cause death during the study period.
Pregnant or lactating female.
Current alcoholism and/or drug abuse.
Other condition which the investigator judges may put the safety of the subject at risk through study participation or which may interfere with the study findings.
Planned move to a location that will complicate participation in the trial through study end.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Mesa	Arizona	85213	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
36068109	Derived	Arora AK, Chinsky K, Keller C, Mayers I, Pascual-Guardia S, Vera MP, Lambert C, Lombardi S, Rondini S, Tian S, Ulloa-Montoya F, Moraschini L, Casula D; NTHi-Mcat-002 study group. A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial. Vaccine. 2022 Sep 29;40(41):5924-5932. doi: 10.1016/j.vaccine.2022.08.053. Epub 2022 Sep 6.
35026180

ID	Title	Description
FG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 27, 2019	Nov 17, 2020

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

Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year

Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.

The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.

Posted

Number

87% Confidence Interval

exacerbations per person-year

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants	OG000278 OG001292

Title

Denominators

Categories

Title	Measurements
	OG0001.22(1.09 to 1.36) OG0011.17(1.06 to 1.3)

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	To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of moderate and severe AECOPDs	Negative Binomial regression	Negative Binomial model with arm, country, gold grade, history of exacerbation and age category as covariates and log time as offset variable	0.8157		Other: Vaccine Efficacy rate	-2.26			2-Sided	87	-18.27	11.58					Other	Vaccine Efficacy is defined as 1 minus the risk ratio (Rvacc / Rcon) based on the number of moderate and severe AECOPD observed in 1 year , with Rvacc = average yearly incidence rate of AECOPD events per subject in the GSK3277511A Group and Rcon = average yearly incidence rate of AECOPD events per subject in the Control group. The objective is to be considered a success if the lower limit of the 87% CI is above 0%.

Primary

Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year

Posted

Number

95% Confidence Interval

exacerbations per person-year

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61

Secondary

Number of Subjects Reported With Each Solicited Local Adverse Event (AE)

Assessed solicited local symptoms were pain, redness and swelling

The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided solicited safey data.

Posted

Count of Participants

Participants

During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Subjects Reported With Each Solicited General AE

Assessed solicited general symptoms were Chills, fatigue, fever [defined as (oral cavity or axillary) temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms [nausea, vomiting, diarrhoea and/or abdominal pain], headache and myalgia.

The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided solicited safey data.

Posted

Count of Participants

Participants

During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units

Secondary

Number of Subjects Reported With Any Unsolicited Adverse Event (AE)

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for any solicited symptoms.

The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided unsolicited safety data.

Posted

Count of Participants

Participants

During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs)

pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided safety data.

Posted

Count of Participants

Participants

From first vaccination (Day 1) up to Study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Subjects Reported With Any Serious Adverse Event (SAE)

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity

The analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with at least one documented study vaccine administration and who provided safety data.

Posted

Count of Participants

Participants

From first vaccination (Day 1) up to Study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The severity of AECOPD can be graded according to the intensity of medical intervention required. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.

Posted

Number

95% Confidence Interval

exacerbations per person-year

During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group

Secondary

Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

The rates of any AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The intention of the analysis of the Rate during 3, 6, 9 and 12 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 and 0-12 months.

Posted

Number

95% Confidence Interval

exacerbations per person-year

During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months, 0-12 months (observation starting 1 month post-Dose 2)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period

The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: It is calculated proportionally to the follow-up time per subject and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for each period considered. The severity of AECOPD can be graded according to the intensity of medical intervention required. Mild = can be controlled with an increase in dosage of regular medications. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.

Posted

Mean

Standard Deviation

exacerbations per person

During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61

Secondary

Number of Subjects With First Moderate or Severe AECOPD

Number of subjects with first occurrence of moderate or severe episode of AECOPD was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

Posted

Count of Participants

Participants

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Subjects With First AECOPD of Any Severity

Number of subjects with first occurrence of any episode of AECOPD of any severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

Posted

Count of Participants

Participants

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Subjects With First AECOPD Classified by Severity

Number of subjects with first occurrence of any episode of AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.

Posted

Count of Participants

Participants

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Days With Moderate and Severe AECOPDs

The length of each AECOPD was tabulated and presented via descriptive statistics (mean, Standard Deviation) and expressed in Days.

Posted

Mean

Standard Deviation

Days

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Days With AECOPDs of Any Severity

The length of each AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Posted

Mean

Standard Deviation

Days

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Days With AECOPDs Classified by Severity

The length of each AECOPDs by severity was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Posted

Mean

Standard Deviation

Days

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD

Posted

Number

95% Confidence Interval

exacerbations per person-year

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity

The rates of AECOPD of any severity were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by polymerase chain reaction (PCR) analysis in sputum samples.

Posted

Number

95% Confidence Interval

exacerbations per person- year

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity

The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: it is calculated proportionally to the follow-up time per subject, and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for the period considered. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples

Posted

Mean

Standard Deviation

exacerbations per person

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD

Number of subjects with first occurrence of moderate or severe NTHI-associated and/or Mcat-associated AECOPD was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

Posted

Count of Participants

Participants

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity

Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD of any severity was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

Posted

Count of Participants

Participants

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity

Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.

Posted

Count of Participants

Participants

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD

The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Posted

Mean

Standard Deviation

Days

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity

The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Posted

Mean

Standard Deviation

Days

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity

The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).

Posted

Mean

Standard Deviation

Days

From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA)

Anti-Protein D (PD) antibody concentrations as determined by ELISA, and expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EU/mL). For anti-PD antibodies, the cut-off of the assay is 153 ELISA Units per millilitre (EU/mL.)

The analysis was performed on the Per-Protocol immuno set for analysis of immunogenicity cohort which includes all vaccinated subjects who complied with the vaccination schedule and who have immunogenicity data for the specified timepoints.

Posted

Geometric Mean

95% Confidence Interval

EU/mL.

At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units

Secondary

Anti-PE Antibody Concentrations as Measured by ELISA

Anti-Protein E (PE) antibody concentrations as determined by ELISA and expressed as GMCs in EU/mL For Anti-PE antibodies, the cut-off of the assay is 16 EU/mL.

Posted

Geometric Mean

95% Confidence Interval

EU/mL.

At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Anti-PilA Antibody Concentrations as Measured by ELISA

Anti-Type IV pilus assembly protein (PilA) antibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-PilA antibodies, the cut-off of the assay is 8 EU/mL.

Posted

Geometric Mean

95% Confidence Interval

EU/mL.

At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts
Participants

Secondary

Anti-UspA2 Antibody Concentrations as Measured by ELISA

Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) aantibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-UspA2 antibodies, the cut-off of the assay is 28 EU/mL.

Posted

Geometric Mean

95% Confidence Interval

EU/mL

At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Units	Counts

Secondary

Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess cell-mediated immunogenicity (CMI) responses. After Peripheral blood mononuclear cell (PBMC) stimulation with the relevant antigen, the frequency of PD specific CD4+ T-cells expressing selected combination of cytokines such as interleukine-2, 13, 17 (IL-2, IL-13, IL-17), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L) are evaluated by flow cytometry and expressed as mean and standard deviation.

The analysis was performed on the Per-Protocol CMI set for analysis of immunogenicity cohort which includes all vaccinated subjects who were complied with the vaccination schedule and who have CMI data for the specified timepoints.

Posted

Mean

Standard Deviation

T cells/million cells

At Day 1, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PE specific CD4+ T-cells expressing selected combination of cytokines such as (IL-2, IL-13, IL-17), IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

Posted

Mean

Standard Deviation

T cells/million cells

At Day 1, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PilA specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

Posted

Mean

Standard Deviation

T cells/million cells

At Day 1, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Secondary

Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data

The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of UspA2 specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.

Posted

Mean

Standard Deviation

T cells/million cells

At Day 1, Day 91, Day 271 and at Day 451

ID	Title	Description
OG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
OG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acute left ventricular failure	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Acute myocardial infarction	Cardiac disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0011 events1 affected302 at risk
Angina pectoris	Cardiac disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Angina unstable	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Arrhythmia	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0005 events4 affected304 at risk EG0012 events2 affected302 at risk
Atrial flutter	Cardiac disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Cardiac failure	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Cardiac failure congestive	Cardiac disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0013 events2 affected302 at risk
Cardiomyopathy	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Coronary artery insufficiency	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Pericardial effusion	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Sinus node dysfunction	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Stress cardiomyopathy	Cardiac disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Supraventricular tachycardia	Cardiac disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Trifascicular block	Cardiac disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Ventricular tachycardia	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Abdominal pain upper	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Dyschezia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Enterovesical fistula	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Ileus	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Ileus paralytic	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Intestinal pseudo-obstruction	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Retroperitoneal haematoma	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Chest pain	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Condition aggravated	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Drug withdrawal syndrome	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Oedema	General disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Cholecystitis acute	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Cholelithiasis	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Cirrhosis alcoholic	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Abdominal abscess	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
CNS ventriculitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Diverticulitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Enterococcal infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Enterocolitis viral	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Graft infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0015 events4 affected302 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0004 events4 affected304 at risk EG0012 events2 affected302 at risk
Metapneumovirus infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0005 events5 affected304 at risk EG00117 events15 affected302 at risk
Pneumonia pneumococcal	Infections and infestations	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Pneumonia pseudomonal	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pneumonia staphylococcal	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Pyelonephritis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Respiratory syncytial virus infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Septic shock	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Tracheobronchitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0013 events3 affected302 at risk
Urosepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0013 events2 affected302 at risk
Wound abscess	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Abdominal wound dehiscence	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Anastomotic complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Drain site complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Exposure to toxic agent	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Femur fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Head injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Hip fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Intentional overdose	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Ligament rupture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Musculoskeletal procedural complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Procedural pneumothorax	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Radius fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Oxygen saturation decreased	Investigations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Weight decreased	Investigations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Acidosis	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Hyperkalaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Hyponatraemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Arthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events1 affected302 at risk
Adenocarcinoma gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Hypopharyngeal cancer stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Laryngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Metastatic gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Penile cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Cerebrospinal fluid leakage	Nervous system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Cerebrovascular accident	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Guillain-Barre syndrome	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Haemorrhage intracranial	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Hemiplegic migraine	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Lumbar radiculopathy	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Ruptured cerebral aneurysm	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Subarachnoid haemorrhage	Nervous system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Transient ischaemic attack	Nervous system disorders	Systematic Assessment	EG0003 events3 affected304 at risk EG0010 events0 affected302 at risk
Device loosening	Product Issues	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0002 events1 affected304 at risk EG0011 events1 affected302 at risk
Haematuria	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Nephrolithiasis	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Urinary incontinence	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Breast mass	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Scrotal inflammation	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0008 events7 affected304 at risk EG0017 events7 affected302 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00055 events41 affected304 at risk EG00183 events53 affected302 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0014 events4 affected302 at risk
Aortic aneurysm	Vascular disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Femoral artery aneurysm	Vascular disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Peripheral arterial occlusive disease	Vascular disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Peripheral artery aneurysm	Vascular disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Peripheral vein occlusion	Vascular disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Thrombophlebitis	Vascular disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Cardiac failure	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Mitral valve prolapse	Cardiac disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Cerumen impaction	Ear and labyrinth disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Ear pain	Ear and labyrinth disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Goitre	Endocrine disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Cataract	Eye disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Dermatochalasis	Eye disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Ocular hyperaemia	Eye disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Retinoschisis	Eye disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Vision blurred	Eye disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Vitreous detachment	Eye disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Abdominal discomfort	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Abdominal pain lower	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Dental caries	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0003 events3 affected304 at risk EG0019 events9 affected302 at risk
Faecaloma	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Gastrointestinal disorder	Gastrointestinal disorders	Systematic Assessment	EG00086 events71 affected304 at risk EG00190 events77 affected302 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Inguinal hernia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Intestinal polyp	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0013 events3 affected302 at risk
Pancreatic disorder	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Toothache	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Asthenia	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Chest discomfort	General disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0012 events2 affected302 at risk
Chills	General disorders	Systematic Assessment	EG00064 events52 affected304 at risk EG00165 events52 affected302 at risk
Drug intolerance	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Fatigue	General disorders	Systematic Assessment	EG000297 events195 affected304 at risk EG001299 events197 affected302 at risk
Feeling hot	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Injection site bruising	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Injection site erythema	General disorders	Systematic Assessment	EG00055 events43 affected304 at risk EG0011 events1 affected302 at risk
Injection site pain	General disorders	Systematic Assessment	EG000324 events213 affected304 at risk EG00131 events30 affected302 at risk
Injection site reaction	General disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Injection site swelling	General disorders	Systematic Assessment	EG00045 events35 affected304 at risk EG0013 events3 affected302 at risk
Malaise	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Oedema peripheral	General disorders	Systematic Assessment	EG0005 events5 affected304 at risk EG0010 events0 affected302 at risk
Pyrexia	General disorders	Systematic Assessment	EG00042 events39 affected304 at risk EG00136 events32 affected302 at risk
Seasonal allergy	Immune system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Acute sinusitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Chronic sinusitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Conjunctivitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Cystitis	Infections and infestations	Systematic Assessment	EG0003 events3 affected304 at risk EG0011 events1 affected302 at risk
Ear infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Erysipelas	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Fungal infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0013 events3 affected302 at risk
Gastroenteritis viral	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Gingivitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Herpes zoster	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0002 events2 affected304 at risk EG0013 events3 affected302 at risk
Kidney infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Labyrinthitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Laryngitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Localised infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Lower respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG00013 events13 affected304 at risk EG00115 events13 affected302 at risk
Oral candidiasis	Infections and infestations	Systematic Assessment	EG0002 events2 affected304 at risk EG0011 events1 affected302 at risk
Oropharyngeal candidiasis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Otitis media acute	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Paronychia	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pharyngitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0013 events3 affected302 at risk
Respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Rhinitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Sinusitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0014 events4 affected302 at risk
Sweat gland infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0004 events4 affected304 at risk EG0013 events3 affected302 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected304 at risk EG0015 events4 affected302 at risk
Viral infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Arthropod bite	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Chest injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Joint injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Meniscus injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Rib fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Skin laceration	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Thermal burn	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Weight increased	Investigations	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Gout	Metabolism and nutrition disorders	Systematic Assessment	EG0002 events1 affected304 at risk EG0010 events0 affected302 at risk
Hyperinsulinaemic hypoglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0011 events1 affected302 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG000153 events115 affected304 at risk EG001116 events94 affected302 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0012 events2 affected302 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0015 events4 affected302 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Synovial cyst	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Tendon disorder	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0012 events2 affected302 at risk
Epilepsy	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Focal dyscognitive seizures	Nervous system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Headache	Nervous system disorders	Systematic Assessment	EG000178 events127 affected304 at risk EG001145 events111 affected302 at risk
Paraesthesia	Nervous system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Post herpetic neuralgia	Nervous system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Post polio syndrome	Nervous system disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Tension headache	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Tremor	Nervous system disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0012 events2 affected302 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Panic attack	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Chromaturia	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Urine odour abnormal	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Bartholin's cyst	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Scrotal pain	Reproductive system and breast disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Scrotal swelling	Reproductive system and breast disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 events5 affected304 at risk EG0013 events3 affected302 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected304 at risk EG0010 events0 affected302 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Increased upper airway secretion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 events3 affected304 at risk EG0010 events0 affected302 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0012 events2 affected302 at risk
Paranasal sinus discomfort	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Pharyngeal erythema	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Sputum discoloured	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Dandruff	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Dermatitis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0012 events2 affected302 at risk
Eczema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Erythema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Pruritus allergic	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Psoriasis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Skin lesion	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0011 events1 affected302 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0000 events0 affected304 at risk EG0011 events1 affected302 at risk
Peripheral venous disease	Vascular disorders	Systematic Assessment	EG0001 events1 affected304 at risk EG0010 events0 affected302 at risk

ID	Term
D012120	Respiration Disorders
D029424	Pulmonary Disease, Chronic Obstructive

ID	Term
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61
BG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.
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	GSK3277511A Group	Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61	1	304	89	304	276	304
EG001	Control Group	Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61.	10	302	99	302	247	302