Study of Pembrolizumab Given With Ipilimumab or Placebo i... | NCT03302234

ID	Type	Description
MK-3475-598	Other Identifier	Merck
KEYNOTE-598	Other Identifier	Merck
2016-004364-20	EudraCT Number

Label	Type	Description	Intervention Names
Pembrolizumab + Ipilimumab	Experimental	Participants receive 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.	Biological: Pembrolizumab Biological: Ipilimumab
Pembrolizumab + Placebo	Active Comparator	Participants receive 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.	Biological: Pembrolizumab Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Administered as an intravenous (IV) infusion every 3 weeks (Q3W)	Pembrolizumab + Ipilimumab Pembrolizumab + Placebo

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. The median survival (in months) and the associated 95% confidence intervals (CIs) were reported using Kaplan-Meier method was used. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) was used to estimate hazard ratio (HR) and 95% CIs for first course study treatment per protocol.	Up to approximately 32 months (through data cut-off date: 01 Sep 2020)
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)	PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in sum of diameters of target lesions. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The median survival (in months) and associated 95% CIs were reported using Kaplan-Meier method. Cox regression model with Efron's method of tie handling with treatment as covariate stratified by ECOG performance status (0 vs. 1), geographic region of the enrolling site (East Asia vs. non-East Asia), and predominant tumor history (squamous vs. non-squamous) was used to estimate HR and 95% CIs for first course study treatment per protocol.	Up to approximately 32 months (through data cut-off date 01 Sep 2020)

Measure	Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 Based on BICR	ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol the ORR was calculated using the Miettinen & Nurminen method stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) for the first course of study treatment.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Cancer Center ( Site 0007)		Phoenix	Arizona	85054	United States
Disney Family Cancer Center ( Site 0035)

PubMed Identifier	Type	Citation	Retractions
33513313	Derived	Boyer M, Sendur MAN, Rodriguez-Abreu D, Park K, Lee DH, Cicin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score >/= 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021 Jul 20;39(21):2327-2338. doi: 10.1200/JCO.20.03579. Epub 2021 Jan 29.

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 11, 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

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. The median survival (in months) and the associated 95% confidence intervals (CIs) were reported using Kaplan-Meier method was used. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) was used to estimate hazard ratio (HR) and 95% CIs for first course study treatment per protocol.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to approximately 32 months (through data cut-off date: 01 Sep 2020)

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).
OG001	Pembrolizumab + Placebo	Participants received 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Units	Counts
Participants	OG000284 OG001284

Title

Denominators

Categories

Title	Measurements
	OG00021.4(16.6 to NA)NA = Upper limit OS was not reached at the time of last disease assessment due to insufficient number of participants with events. OG00121.9(18.0 to NA)NA = Upper limit OS was not reached at the time of last disease assessment due to insufficient number of participants with events.

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		Log Rank		0.74156	One-sided p-value based on log-rank test stratified by ECOG, geographic region of the enrolling site, and predominant tumor history.	Hazard Ratio (HR)	1.08			2-Sided	95	0.85	1.37			Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG, geographic region of the enrolling site, and predominant tumor history.		Other

Primary

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)

PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in sum of diameters of target lesions. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The median survival (in months) and associated 95% CIs were reported using Kaplan-Meier method. Cox regression model with Efron's method of tie handling with treatment as covariate stratified by ECOG performance status (0 vs. 1), geographic region of the enrolling site (East Asia vs. non-East Asia), and predominant tumor history (squamous vs. non-squamous) was used to estimate HR and 95% CIs for first course study treatment per protocol.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to approximately 32 months (through data cut-off date 01 Sep 2020)

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Secondary

Objective Response Rate (ORR) Per RECIST 1.1 Based on BICR

ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol the ORR was calculated using the Miettinen & Nurminen method stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) for the first course of study treatment.

All randomized participants

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to approximately 32 months (data cut-off date 01 Sep 2020)

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Secondary

Duration of Response (DOR) Per RECIST 1.1 Based on BICR

For participants who demonstrated a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. Per protocol, the DOR for all participants who experienced a CR or PR was presented for the first course of study treatment.

All randomized participants with confirmed complete response or partial response

Posted

Median

95% Confidence Interval

Months

Up to approximately 32 months (data cut-off date 01 Sep 2020)

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Secondary

Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath

TTD was defined as the time to the first onset of a 10-point or greater score deterioration from baseline in any one of the 3 symptoms (cough, pain in chest or shortness of breath), confirmed by a second adjacent 10-point or greater score deterioration from baseline. Cough was based on EORTC QLQ-LC13 question 1, pain in chest was based on EORTC QLQ-LC13 question 10, and shortness of breath was based on EORTC QLQ-C30 question 8. Per protocol, TTD was reported for first course study treatment.

All participants randomized who received at least one dose of study treatment and had at least one EORTC QLQ-LC13 and EORTC QLQ-C30 available.

Posted

Median

95% Confidence Interval

Months

Up to approximately 32 months (data cut-off date 01 Sep 2020)

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Secondary

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Per protocol, the number of participants who experienced an AE were reported for the first course of study treatment and follow up.

All randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 27 months

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Secondary

Number of Participants Who Discontinued Study Treatment Due to an AE

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Per protocol, the number of participants who discontinued study treatment due to an AE were reported for the first course of study treatment.

All randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score to Week 18

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. Per protocol, the change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score were presented for first course study treatment.

All randomized participants who received at least one dose of study treatment and had at least one EORTC QLQ-C30 assessment available.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline, Week 18

ID	Title	Description
OG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Atrial flutter	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events1 affected281 at risk EG0020 events0 affected18 at risk
Atrial tachycardia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Autoimmune pericarditis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Cardiac arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Cardiac failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Cardiac tamponade	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0021 events1 affected18 at risk
Myocardial infarction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0005 events4 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Myocarditis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Pericardial effusion	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0014 events4 affected281 at risk EG0020 events0 affected18 at risk
Pericarditis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0003 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Right ventricular failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0005 events5 affected282 at risk EG0013 events3 affected281 at risk EG0020 events0 affected18 at risk
Adrenocortical insufficiency acute	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hypophysitis	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Hypothyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Lymphocytic hypophysitis	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Thyroiditis	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cataract	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events1 affected281 at risk EG0020 events0 affected18 at risk
Ophthalmoplegia	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Autoimmune colitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 events3 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Colitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00010 events7 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0006 events6 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Enteritis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Gastrointestinal toxicity	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Immune-mediated enterocolitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Intussusception	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events1 affected281 at risk EG0020 events0 affected18 at risk
Melaena	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Salivary gland calculus	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Asthenia	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events1 affected281 at risk EG0020 events0 affected18 at risk
Chest pain	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Death	General disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0014 events4 affected281 at risk EG0020 events0 affected18 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
General physical health deterioration	General disorders	MedDRA 25.0	Systematic Assessment	EG0003 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Non-cardiac chest pain	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0005 events5 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Sudden death	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Cholelithiasis migration	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cholestatic liver injury	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Hepatitis acute	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hypersensitivity	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Infusion related hypersensitivity reaction	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Adrenalitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Bronchitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0010 events0 affected281 at risk EG0021 events1 affected18 at risk
Cellulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Chronic sinusitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Diverticulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Diverticulitis intestinal haemorrhagic	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Empyema	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Encephalitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Gastroenteritis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0013 events3 affected281 at risk EG0020 events0 affected18 at risk
Infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Influenza	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0004 events3 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Oral candidiasis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00024 events21 affected282 at risk EG00124 events20 affected281 at risk EG0020 events0 affected18 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0014 events3 affected281 at risk EG0020 events0 affected18 at risk
Pneumonia legionella	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Postoperative wound infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Psoas abscess	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0003 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Pyelonephritis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Renal abscess	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Septic shock	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Soft tissue infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Thrombophlebitis septic	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Acetabulum fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Ilium fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Skull fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Weight decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Eosinophilic fasciitis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Osteoporotic fracture	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Polymyalgia rheumatica	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Vertebral lesion	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Ductal adenocarcinoma of pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Laryngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Small intestine carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Autoimmune encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Balance disorder	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Brain oedema	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cerebral infarction	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0022 events2 affected18 at risk
Dysaesthesia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Facial paralysis	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hydrocephalus	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Peripheral sensorimotor neuropathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Sensory disturbance	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Spinal cord compression	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Syncope	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Anxiety	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Confusional state	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Mental status changes	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0003 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Autoimmune nephritis	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Nephrotic syndrome	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Proteinuria	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Renal failure	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected282 at risk EG0017 events6 affected281 at risk EG0020 events0 affected18 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0006 events5 affected282 at risk EG0015 events5 affected281 at risk EG0020 events0 affected18 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0003 events2 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected282 at risk EG0013 events3 affected281 at risk EG0020 events0 affected18 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00020 events20 affected282 at risk EG00110 events10 affected281 at risk EG0020 events0 affected18 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0005 events5 affected282 at risk EG00110 events10 affected281 at risk EG0020 events0 affected18 at risk
Pulmonary granuloma	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0013 events3 affected281 at risk EG0020 events0 affected18 at risk
Dermatitis exfoliative	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Angiopathy	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Aortic dissection	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Embolism	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Haematoma	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected281 at risk EG0020 events0 affected18 at risk
Hypotension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0020 events0 affected18 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events2 affected281 at risk EG0020 events0 affected18 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG00050 events40 affected282 at risk EG00157 events40 affected281 at risk EG0021 events1 affected18 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0015 events5 affected281 at risk EG0021 events1 affected18 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG00026 events25 affected282 at risk EG00126 events18 affected281 at risk EG0021 events1 affected18 at risk
Hypophysitis	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0008 events8 affected282 at risk EG0013 events2 affected281 at risk EG0021 events1 affected18 at risk
Hypothyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG00048 events43 affected282 at risk EG00137 events34 affected281 at risk EG0021 events1 affected18 at risk
Diplopia	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0010 events0 affected281 at risk EG0021 events1 affected18 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00046 events39 affected282 at risk EG00157 events52 affected281 at risk EG0020 events0 affected18 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG000105 events70 affected282 at risk EG00174 events46 affected281 at risk EG0021 events1 affected18 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00017 events15 affected282 at risk EG00119 events18 affected281 at risk EG0021 events1 affected18 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected281 at risk EG0021 events1 affected18 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00067 events51 affected282 at risk EG00151 events40 affected281 at risk EG0020 events0 affected18 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00044 events30 affected282 at risk EG00135 events27 affected281 at risk EG0020 events0 affected18 at risk
Asthenia	General disorders	MedDRA 25.0	Systematic Assessment	EG00066 events51 affected282 at risk EG00160 events44 affected281 at risk EG0020 events0 affected18 at risk
Chest pain	General disorders	MedDRA 25.0	Systematic Assessment	EG00015 events15 affected282 at risk EG00131 events27 affected281 at risk EG0021 events1 affected18 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG00066 events47 affected282 at risk EG00158 events50 affected281 at risk EG0021 events1 affected18 at risk
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG00031 events24 affected282 at risk EG00114 events13 affected281 at risk EG0020 events0 affected18 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG00040 events34 affected282 at risk EG00134 events27 affected281 at risk EG0020 events0 affected18 at risk
Contrast media allergy	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0012 events2 affected281 at risk EG0021 events1 affected18 at risk
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected282 at risk EG0014 events4 affected281 at risk EG0021 events1 affected18 at risk
Cystitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0006 events5 affected282 at risk EG0015 events4 affected281 at risk EG0021 events1 affected18 at risk
Nasopharyngitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0008 events7 affected282 at risk EG00116 events15 affected281 at risk EG0020 events0 affected18 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00014 events13 affected282 at risk EG00117 events16 affected281 at risk EG0020 events0 affected18 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00020 events11 affected282 at risk EG00119 events15 affected281 at risk EG0020 events0 affected18 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00041 events31 affected282 at risk EG00126 events20 affected281 at risk EG0021 events1 affected18 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00044 events37 affected282 at risk EG00115 events15 affected281 at risk EG0021 events1 affected18 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00022 events20 affected282 at risk EG00113 events12 affected281 at risk EG0020 events0 affected18 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0011 events1 affected281 at risk EG0021 events1 affected18 at risk
Blood creatinine increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00022 events16 affected282 at risk EG00122 events16 affected281 at risk EG0022 events1 affected18 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0008 events2 affected282 at risk EG0014 events3 affected281 at risk EG0022 events1 affected18 at risk
Blood phosphorus decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0015 events4 affected281 at risk EG0021 events1 affected18 at risk
C-reactive protein increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected282 at risk EG0011 events1 affected281 at risk EG0021 events1 affected18 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0009 events9 affected282 at risk EG00112 events10 affected281 at risk EG0021 events1 affected18 at risk
Weight decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG00033 events29 affected282 at risk EG00129 events26 affected281 at risk EG0021 events1 affected18 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00073 events61 affected282 at risk EG00144 events39 affected281 at risk EG0020 events0 affected18 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00025 events17 affected282 at risk EG00125 events16 affected281 at risk EG0020 events0 affected18 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00015 events11 affected282 at risk EG00129 events18 affected281 at risk EG0020 events0 affected18 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0009 events5 affected282 at risk EG0013 events3 affected281 at risk EG0021 events1 affected18 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00017 events8 affected282 at risk EG00114 events7 affected281 at risk EG0021 events1 affected18 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00021 events18 affected282 at risk EG0016 events6 affected281 at risk EG0020 events0 affected18 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00030 events22 affected282 at risk EG00128 events16 affected281 at risk EG0020 events0 affected18 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00013 events8 affected282 at risk EG00114 events11 affected281 at risk EG0021 events1 affected18 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00022 events18 affected282 at risk EG00119 events14 affected281 at risk EG0021 events1 affected18 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0007 events7 affected282 at risk EG0019 events7 affected281 at risk EG0021 events1 affected18 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00046 events39 affected282 at risk EG00155 events45 affected281 at risk EG0021 events1 affected18 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00036 events31 affected282 at risk EG00134 events29 affected281 at risk EG0020 events0 affected18 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00022 events18 affected282 at risk EG00125 events21 affected281 at risk EG0021 events1 affected18 at risk
Amnesia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0012 events2 affected281 at risk EG0021 events1 affected18 at risk
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG00014 events14 affected282 at risk EG00120 events18 affected281 at risk EG0020 events0 affected18 at risk
Anxiety	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG00010 events8 affected282 at risk EG00119 events16 affected281 at risk EG0021 events1 affected18 at risk
Insomnia	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG00023 events18 affected282 at risk EG00124 events23 affected281 at risk EG0020 events0 affected18 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected282 at risk EG0011 events1 affected281 at risk EG0021 events1 affected18 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00053 events47 affected282 at risk EG00177 events58 affected281 at risk EG0021 events1 affected18 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00049 events44 affected282 at risk EG00151 events44 affected281 at risk EG0020 events0 affected18 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00015 events13 affected282 at risk EG00127 events24 affected281 at risk EG0021 events1 affected18 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected282 at risk EG0010 events0 affected281 at risk EG0021 events1 affected18 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0009 events9 affected282 at risk EG00120 events18 affected281 at risk EG0020 events0 affected18 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG00012 events8 affected282 at risk EG0018 events7 affected281 at risk EG0021 events1 affected18 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG00015 events15 affected282 at risk EG00118 events18 affected281 at risk EG0020 events0 affected18 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG00099 events69 affected282 at risk EG00178 events58 affected281 at risk EG0020 events0 affected18 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected282 at risk EG0013 events3 affected281 at risk EG0021 events1 affected18 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG00078 events57 affected282 at risk EG00163 events45 affected281 at risk EG0020 events0 affected18 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0004 events3 affected282 at risk EG0012 events1 affected281 at risk EG0021 events1 affected18 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG00029 events24 affected282 at risk EG00113 events12 affected281 at risk EG0020 events0 affected18 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body
C563326	Diabetes Mellitus, Insulin-Dependent, 12

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Pembrolizumab + Ipilimumab	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).
BG001	Pembrolizumab + Placebo	Participants received 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).
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	Pembrolizumab+Ipilimumab (First Course)	Participants received 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued ipilimumab and participants who remained on treatment received open-label pembrolizumab only. Eligible participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) or who attained complete response (CR) but experienced progression of disease (PD), initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year).	191	284	146	282	251	282
EG001	Pembrolizumab+Placebo (First Course)	Participants received 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only.	188	284	114	281	232	281
EG002	Pembrolizumab + Placebo (Second Course)	Participants received 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment. Per Amendment (AM) 6, (effective date: 11-Dec-2020), participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only.	4	18	4	18	10	18