Study to Assess Safety, Tolerability and Clinical Activit... | NCT03150810

ID	Type	Description	Link
2017-001553-14	EudraCT Number

Name	Class
Myriad Genetics, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7)	Experimental	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle	Drug: Pamiparib Drug: Temozolomide
Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Experimental	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle	Drug: Pamiparib Drug: Temozolomide
Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Experimental	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle	Drug: Pamiparib Drug: Temozolomide
Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)	Experimental	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle	Drug: Pamiparib Drug: Temozolomide
Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)	Experimental

Name	Type	Description	Arm Group Labels	Other Names
Pamiparib	Drug	Administered by mouth as a capsule twice daily	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7) Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)

Measure	Description	Time Frame
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)	A DLT is defined as one of the following toxicities occurring during the DLT assessment window: Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting >7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting > 3 days and requiring transfusion, or any decreased platelet count <15,000/mm3/ <15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)	From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
Number of Participants Experiencing Adverse Events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where BOR is defined as the best response recorded from the first postbaseline tumor assessment until data cutoff date, disease progression or start of new anticancer treatment.	Up to approximately 5 years and 10 months

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Pamiparib	Pamiparib pharmakokinetic (PK) parameters were assessed in the first 20 participants enrolled in the dose escalation phase after a single dose on Day -2 and at steady state in combination with TMZ on Day 15.	2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose (each cycle is 28 days)

Name	Affiliation	Role
Study Director	BeiGene	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Start Midwest		Grand Rapids	Michigan	49503	United States
Washington University in St Louis

ID	Title	Description
FG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
FG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 19, 2020	Apr 25, 2024

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

Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)

A DLT is defined as one of the following toxicities occurring during the DLT assessment window:

Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting >7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting > 3 days and requiring transfusion, or any decreased platelet count <15,000/mm3/ <15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)

The dose-escalation safety analysis set comprised all dose-escalation phase participants who received pamiparib and/or TMZ.

Posted

Count of Participants

Participants

From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
OG003	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle
OG004	Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle
OG005	Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle
OG006	Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28)	Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
OG007	Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28)	Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle

Units	Counts
Participants	OG0004 OG00113 OG0029 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Primary

Number of Participants Experiencing Adverse Events (AEs)

Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03

The Safety Analysis Set included all participants who received any dose of pamiparib and/or TMZ.

Posted

Count of Participants

Participants

From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle

Primary

Objective Response Rate (ORR)

ORR is defined as the percentage of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where BOR is defined as the best response recorded from the first postbaseline tumor assessment until data cutoff date, disease progression or start of new anticancer treatment.

The Efficacy Analysis Set included all participants who were in the safety analysis set, had measurable disease at baseline and had at least one postbaseline tumor assessment unless discontinued treatment due to clinical progression or death prior to tumor assessment.

Posted

Number

90% Confidence Interval

percentage of participants

Up to approximately 5 years and 10 months

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)

Secondary

Maximum Observed Plasma Concentration (Cmax) of Pamiparib

Pamiparib pharmakokinetic (PK) parameters were assessed in the first 20 participants enrolled in the dose escalation phase after a single dose on Day -2 and at steady state in combination with TMZ on Day 15.

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; per the prespecified analysis, participants were analyzed in one group, regardless of dose of TMZ they received. Only 13 participants had data available for calculation of Cmax on Day 15.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose (each cycle is 28 days)

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Plasma Trough Concentrations of Pamiparib (Ctrough)

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; per the prespecified analysis, participants were analyzed in one group, regardless of dose of TMZ they received. Only 14 participants had data available for calculation of Ctrough on Day 15.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 15 predose

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Time to Reach Cmax (Tmax) of Pamiparib

Posted

Median

Full Range

hours

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; per the prespecified analysis participants were analyzed in one group, regardless of dose of TMZ they received. Only 8 participants had available data to calculate AUC0-4 on Day 15.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, and 4 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; AUC0-inf could only be calculated for 15 participants.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Terminal Elimination Half-life (t1/2) of Pamiparib

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; Only 17 participants had data available to calculate T1/2.

Posted

Geometric Mean

Full Range

hours

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Apparent Clearance (CL/F) of Pamiparib

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; Only 15 participants had data available to calculate CL/F.

Posted

Geometric Mean

Geometric Coefficient of Variation

L/h

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib

The pamiparib pharmacokinetic analysis included the first 20 participants enrolled in the dose escalation phase; Only 15 participants had data available to calculate Vz/F.

Posted

Geometric Mean

Geometric Coefficient of Variation

liters

2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)

ID	Title	Description
OG000	Pamiparib	The first 20 participants enrolled in the dose-escalation phase received a single dose of 60 mg pamiparib on Day -2, prior to initiating twice daily dosing with 60 mg pamiparib and TMZ per assigned treatment group on Day 1.

Units	Counts
Participants	OG000

Secondary

Plasma Concentration of Temozolomide (TMZ)

PK Analysis Set: includes participants who received any dose of TMZ and contributed at least one plasma concentration.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7

ID	Title	Description
OG000	TMZ 20 mg	Participants who received 20 mg TMZ orally once a day.
OG001	TMZ 40 mg	Participants who received 40 mg TMZ orally once a day.
OG002	TMZ 60 mg	Participants who received 60 mg TMZ orally once a day.
OG003	TMZ 80 mg	Participants who received 80 mg TMZ orally once a day.
OG004	TMZ 100 mg	Participants who received 100 mg TMZ orally once a day.

Secondary

Disease Control Rate (DCR)

DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD) based on investigator assessment using RECIST v1.1.

Efficacy Analysis Set

Posted

Number

90% Confidence Interval

percentage of participants

Up to approximately 5 years and 10 months

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
OG003	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)

Secondary

Duration of Response (DOR)

DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to disease progression or death due to any cause, whichever occurs earlier, based on investigator assessment using RECIST v1.1. Only responders will be included in the assessment.

Efficacy Analysis Set

Posted

Median

90% Confidence Interval

months

Up to approximately 5 years and 10 months

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
OG003

Secondary

Progression Free Survival (PFS)

PFS is defined as the time (months) from the date of the first dose of combination treatment to disease progression or death due to any cause, whichever occurs first, based on investigator assessment using RECIST v1.1

Efficacy Analysis Set

Posted

Median

90% Confidence Interval

months

Up to approximately 5 years and 10 months)

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
OG003	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)

Secondary

Overall Survival (OS)

OS is defined as the time from the date of the first dose of combination treatment to death due to any cause.

The Safety Analysis Set included all participants who received any dose of pamiparib and/or TMZ.

Posted

Median

90% Confidence Interval

months

Up to approximately 5 years and 10 months

ID	Title	Description
OG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
OG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
OG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
OG003	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG0030 events0 affected3 at risk EG0040 events0 affected3 at risk EG0050 events0 affected14 at risk EG0060 events0 affected14 at risk EG0070 events0 affected6 at risk EG0082 events2 affected21 at risk EG0091 events1 affected4 at risk EG0100 events0 affected22 at risk EG0110 events0 affected1 at risk EG0121 events1 affected25 at risk
Febrile neutropenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Neutropenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Right-to-left cardiac shunt	Congenital, familial and genetic disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Abdominal pain	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0020 events0 affected9 at risk EG003
Ascites	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Constipation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dysphagia	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gastric perforation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gastrointestinal obstruction	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Large intestine perforation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oesophagitis	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Asthenia	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Fatigue	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pyrexia	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Abdominal abscess	Infections and infestations	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Appendicitis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Biliary sepsis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
COVID-19	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Endocarditis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Groin abscess	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Infectious pleural effusion	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Influenza	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pneumocystis jirovecii infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pneumonia	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Respiratory tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Sepsis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Urinary tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Fall	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Stoma site haemorrhage	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Alanine aminotransferase increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Aspartate aminotransferase increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Ataxia	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cerebrovascular accident	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Precerebral artery embolism	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Acute kidney injury	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Haematuria	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hydronephrosis	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Superior vena cava syndrome	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG00111 events8 affected13 at risk EG0028 events5 affected9 at risk EG0038 events2 affected3 at risk EG0044 events3 affected3 at risk EG00515 events10 affected14 at risk EG00610 events6 affected14 at risk EG0074 events3 affected6 at risk EG00815 events12 affected21 at risk EG0094 events2 affected4 at risk EG01018 events13 affected22 at risk EG0114 events1 affected1 at risk EG01225 events16 affected25 at risk
Leukopenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0002 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Neutropenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0018 events4 affected13 at risk EG0025 events3 affected9 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0003 events1 affected4 at risk EG00110 events5 affected13 at risk EG0025 events4 affected9 at risk EG003
Thrombocytosis	Blood and lymphatic system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Aortic valve disease	Cardiac disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Palpitations	Cardiac disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Sinus bradycardia	Cardiac disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Tachycardia	Cardiac disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Deafness unilateral	Ear and labyrinth disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Ear pain	Ear and labyrinth disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Vertigo	Ear and labyrinth disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Adrenal insufficiency	Endocrine disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cataract	Eye disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Glaucoma	Eye disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Iridocyclitis	Eye disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Ocular hyperaemia	Eye disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Photophobia	Eye disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Vision blurred	Eye disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Vitreous floaters	Eye disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Abdominal distension	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Abdominal pain	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0022 events2 affected9 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Anal inflammation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Anorectal discomfort	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Ascites	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cheilitis	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Constipation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0015 events3 affected13 at risk EG0024 events3 affected9 at risk EG003
Dry mouth	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dyspepsia	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Dysphagia	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Eructation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Flatulence	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gastritis	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Gingival bleeding	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Haematochezia	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Nausea	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0003 events3 affected4 at risk EG00112 events9 affected13 at risk EG0025 events5 affected9 at risk EG003
Odynophagia	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oesophageal pain	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oesophagitis	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oral pain	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Regurgitation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Saliva altered	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Small intestinal perforation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Stomatitis	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Tongue pigmentation	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Toothache	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Vomiting	Gastrointestinal disorders	meddra 25.0	Systematic Assessment	EG0002 events1 affected4 at risk EG0015 events5 affected13 at risk EG0021 events1 affected9 at risk EG003
Asthenia	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Axillary pain	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Chest pain	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Chills	General disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Early satiety	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Fatigue	General disorders	meddra 25.0	Systematic Assessment	EG0002 events2 affected4 at risk EG00110 events9 affected13 at risk EG0025 events5 affected9 at risk EG003
Gait disturbance	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Localised oedema	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Malaise	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Non-cardiac chest pain	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Oedema peripheral	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0022 events2 affected9 at risk EG003
Pain	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Peripheral swelling	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pyrexia	General disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0012 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Sluggishness	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Vascular device occlusion	General disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Gallbladder obstruction	Hepatobiliary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hepatomegaly	Hepatobiliary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Seasonal allergy	Immune system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Bronchitis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
COVID-19	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Clostridium difficile infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cystitis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gastroenteritis viral	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Groin abscess	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Groin infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Herpes zoster	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Infected bite	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Influenza	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Lower respiratory tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Nasopharyngitis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Onychomycosis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oral herpes	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oropharyngeal candidiasis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pneumonia	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Respiratory tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Sinusitis	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Tooth infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Upper respiratory tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Urinary tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Contusion	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0020 events0 affected9 at risk EG003
Fall	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Alanine aminotransferase increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Aspartate aminotransferase increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0021 events1 affected9 at risk EG003
Blood alkaline phosphatase increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0022 events2 affected9 at risk EG003
Blood bilirubin increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events2 affected13 at risk EG0020 events0 affected9 at risk EG003
Blood calcium decreased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Blood creatinine increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Gamma-glutamyltransferase increased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Lymphocyte count decreased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Neutrophil count decreased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0022 events2 affected9 at risk EG003
Platelet count decreased	Investigations	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0025 events3 affected9 at risk EG003
Weight decreased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0022 events2 affected9 at risk EG003
White blood cell count decreased	Investigations	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0023 events3 affected9 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0016 events6 affected13 at risk EG0022 events2 affected9 at risk EG003
Dehydration	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0013 events3 affected13 at risk EG0021 events1 affected9 at risk EG003
Gout	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0022 events1 affected9 at risk EG003
Vitamin B12 deficiency	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0014 events4 affected13 at risk EG0020 events0 affected9 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events3 affected13 at risk EG0021 events1 affected9 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Osteopenia	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0021 events1 affected9 at risk EG003
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Aphasia	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Areflexia	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Balance disorder	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cognitive disorder	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Depressed level of consciousness	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dizziness	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Dizziness postural	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Dysaesthesia	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dysarthria	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dysgeusia	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected13 at risk EG0021 events1 affected9 at risk EG003
Headache	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events4 affected13 at risk EG0020 events0 affected9 at risk EG003
Hemiparesis	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Lethargy	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Lumbar radiculopathy	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Mental impairment	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Multiple sclerosis	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Paraparesis	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Parosmia	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Sciatica	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Somnolence	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Taste disorder	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Tremor	Nervous system disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Anxiety	Psychiatric disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Depression	Psychiatric disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Hallucination	Psychiatric disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Insomnia	Psychiatric disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected13 at risk EG0021 events1 affected9 at risk EG003
Acute kidney injury	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Dysuria	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Haematuria	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Nephrolithiasis	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Nocturia	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pollakiuria	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Proteinuria	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Renal colic	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Urethral stenosis	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Urinary incontinence	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Urinary retention	Renal and urinary disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Heavy menstrual bleeding	Reproductive system and breast disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Nipple pain	Reproductive system and breast disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Aphonia	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0002 events2 affected4 at risk EG0012 events2 affected13 at risk EG0022 events1 affected9 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0013 events3 affected13 at risk EG0021 events1 affected9 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0020 events0 affected9 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected13 at risk EG0021 events1 affected9 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Increased bronchial secretion	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Increased upper airway secretion	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Nasal inflammation	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Onychoclasis	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Rash	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Xanthoma	Skin and subcutaneous tissue disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Capillary fragility	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Deep vein thrombosis	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected13 at risk EG0020 events0 affected9 at risk EG003
Haematoma	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hot flush	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0021 events1 affected9 at risk EG003
Hypertension	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Hypotension	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003
Peripheral venous disease	Vascular disorders	meddra 25.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected13 at risk EG0020 events0 affected9 at risk EG003

ID	Title	Description
BG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
BG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
BG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
BG003	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle
BG004	Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle
BG005	Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle
BG006	Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28)	Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
BG007	Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28)	Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
BG008	Dose Expansion: Gastric Cancer	Participants with gastric or gastroesophageal junction cancer received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
BG009	Dose Expansion: Ovarian Cancer	Participants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
BG010	Dose Expansion: SCLC	Participants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
BG011	Dose Expansion: TNBC	Participants with triple negative breast cancer (TNBC) received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
BG012	Dose Expansion: Other HRD+ Cancers	Participants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
BG013	Total	Total of all reporting groups

ID	Term
D010051	Ovarian Neoplasms
D064726	Triple Negative Breast Neoplasms
D055752	Small Cell Lung Carcinoma
D013274	Stomach Neoplasms
D006258	Head and Neck Neoplasms
D004938	Esophageal Neoplasms
D012509	Sarcoma
D002289	Carcinoma, Non-Small-Cell Lung

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders
D001943	Breast Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D013272	Stomach Diseases
D004935	Esophageal Diseases
D018204	Neoplasms, Connective and Soft Tissue
D009370	Neoplasms by Histologic Type

ID	Term
D003606	Dacarbazine
D014226	Triazenes
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle	4	4	1	4	4	4
EG001	Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle	8	13	4	13	13	13
EG002	Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle	7	9	1	9	9	9
EG003	Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle	2	3	2	3	3	3
EG004	Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle	2	3	2	3	3	3
EG005	Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)	Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle	10	14	5	14	14	14
EG006	Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28)	Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle	8	14	5	14	14	14
EG007	Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28)	Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle	6	6	0	6	6	6
EG008	Dose Expansion: Gastric Cancer	Participants with gastric or gastroesophageal junction cancer received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle	18	21	9	21	20	21
EG009	Dose Expansion: Ovarian Cancer	Participants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle	3	4	3	4	4	4
EG010	Dose Expansion: SCLC	Participants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle	19	22	9	22	22	22
EG011	Dose Expansion: TNBC	Participants with triple negative breast cancer (TNBC) received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle	1	1	0	1	1	1
EG012	Dose Expansion: Other HRD+ Cancers	Participants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg once daily administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle	19	25	9	25	24	25