A Phase I Clinical Study With Investigational Compound LT... | NCT02711345

ID	Type	Description	Link
2015-003614-24	EudraCT Number

Label	Type	Intervention Names
Escalation	Experimental	Drug: LTT462
Expansion Group 1	Experimental	Drug: LTT462
Expansion Group 2	Experimental	Drug: LTT462
Expansion Group 3	Experimental	Drug: LTT462
Expansion Group 4	Experimental	Drug: LTT462

Name	Type	Description	Arm Group Labels	Other Names
LTT462	Drug	ERK Inhibitor	Escalation Expansion Group 1 Expansion Group 2 Expansion Group 3 Expansion Group 4

Measure	Description	Time Frame
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.	Up to 2.8 years
Percentage of Participants With Dose Limiting Toxicities (DLTs)	Percentage of participants with dose limiting toxicity were reported.	Up to 2.8 years
Percentage of Participants With at Least One Dose Reduction	Percentage of participants with at least one dose reduction were reported.	Up to 2.8 years
Percentage of Participants With at Least One Dose Interruptions	Percentage of participants with at least dose interruptions were reported.	Up to 2.8 years
Dose Intensity Received by Participants	Dose intensity of LTT462 received by treatment group was reported.	Up to 2.8 years

Measure	Description	Time Frame
Percentage of Participants With Overall Response Rate (ORR)	Percentage of participants with overall response rate were reported.	Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Percentage of Participants With Disease Control Rate (DCR)

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		New York	New York	10065	United States
Novartis Investigative Site

ID	Title	Description
FG000	LTT462 45 mg QD	Participants received LTT462 45 milligram (mg) once daily (QD)
FG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 13, 2018	May 21, 2019

ID	Title	Description
BG000	LTT462 45 mg QD	Participants received 45 mg LTT462 once QD as oral capsules.
BG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
BG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
BG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
BG004	LTT462 300 mg QD	Participants received 300 mg LTT462 QD as oral capsules.
BG005	LTT462 400 mg QD	Participants received 400 mg LTT462 QD as oral capsules.
BG006	LTT462 450 mg QD	Participants received 450 mg LTT462 QD as oral capsules.
BG007	LTT462 600 mg QD	Participants received 600 mg LTT462 QD as oral capsules.
BG008	LTT462 150 mg BID	Participants received 150 mg LTT462 BID as oral capsules.
BG009	LTT462 200 mg BID	Participants received 200 mg LTT462 BID as oral capsules.
BG010	Total	Total of all reporting groups

Units	Counts
Participants	BG0002 BG0013 BG0026 BG0034 BG0048 BG0056 BG00612 BG0076 BG0086 BG00912 BG01065

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

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.

The safety set included all participants who had received at least one dose of LTT462.

Posted

Number

Percentage of participants

Up to 2.8 years

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD	Participants received 300 mg LTT462 QD as oral capsules.
OG005	LTT462 400 mg QD	Participants received 400 mg LTT462 QD as oral capsules.
OG006	LTT462 450 mg QD	Participants received 450 mg LTT462 QD as oral capsules.
OG007	LTT462 600 mg QD	Participants received 600 mg LTT462 QD as oral capsules.
OG008	LTT462 150 mg BID	Participants received 150 mg LTT462 BID as oral capsules.
OG009	LTT462 200 mg BID	Participants received 200 mg LTT462 BID as oral capsules.

Units	Counts
Participants	OG0002 OG0013 OG0026 OG003

Title

Denominators

Categories

AEs

Title	Measurements
	OG0002 OG0013 OG0026 OG003

Primary

Percentage of Participants With Dose Limiting Toxicities (DLTs)

Percentage of participants with dose limiting toxicity were reported.

The dose determining set included all participants from the safety set enrolled in the escalation part of the study who, during the first 28 days of dosing, had received at least 75 percent of the planned daily doses of LTT462 and had had sufficient safety evaluations, or had experienced a DLT.

Posted

Number

Percentage of participants

Up to 2.8 years

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 once QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.

Primary

Percentage of Participants With at Least One Dose Reduction

Percentage of participants with at least one dose reduction were reported.

The safety set included all participants who had received at least one dose of LTT462.

Posted

Number

Percentage of participants

Up to 2.8 years

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD	Participants received 300 mg LTT462 QD as oral capsules.

Primary

Percentage of Participants With at Least One Dose Interruptions

Percentage of participants with at least dose interruptions were reported.

The safety set included all participants who had received at least one dose of LTT462.

Posted

Number

Percentage of participants

Up to 2.8 years

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD	Participants received 300 mg LTT462 QD as oral capsules.

Primary

Dose Intensity Received by Participants

Dose intensity of LTT462 received by treatment group was reported.

The safety set included all participants who had received at least one dose of LTT462.

Posted

Mean

Standard Deviation

milligram per day (mg/day)

Up to 2.8 years

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD	Participants received 300 mg LTT462 QD as oral capsules.

Secondary

Percentage of Participants With Overall Response Rate (ORR)

Percentage of participants with overall response rate were reported.

The full analysis set included all participants who had received at least one dose of LTT462.

Posted

Number

95% Confidence Interval

Percentage of participants

Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD

Secondary

Percentage of Participants With Disease Control Rate (DCR)

Percentage of participants with disease control rate were reported.

The full analysis set included all participants who had received at least one dose of LTT462.

Posted

Number

95% Confidence Interval

Percentage of participants

Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD

Secondary

Duration of Response (DOR)

DOR is defined as the time between the date of the first documented response (complete response [CR] or partial response [PR]) and the date of progression.

As there were no participant achieving response (CR or PR) during escalation phase of the study (only stable disease was achieved). Therefore the evaluation of duration of response could not be performed.

Posted

Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004

Secondary

Progression Free Survival (PFS)

Median time for progression free survival was reported.

The full analysis set included all participants who had received at least one dose of LTT462.

Posted

Median

95% Confidence Interval

months

Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD

Secondary

Overall Survival (OS) - Only for Dose Expansion Phase

Median time for overall survival, only for dose expansion phase was reported.

Overall survival was not evaluated because the study ended before enrolling into the dose-expansion part.

Posted

Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.
OG004	LTT462 300 mg QD

Secondary

The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462

Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration expressed in mass x volume-1.

Pharmacokinetic (PK) analysis set (PAS) included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'n' number analyzed signifies number of participants who were evaluable at each time point.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

day 1, day 15

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD

Secondary

Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462

AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass * time *volume^-1

PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'N' number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour*nanogram per milliliter (h*ng/mL)

Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD

Secondary

The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462

Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.

PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'n' number analyzed signifies number of participants who were evaluable at each time point.

Posted

Median

Full Range

hour

day 1, day 15

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.

Secondary

Elimination Half-life (T1/2) of LTT462

T1/2 is the Elimination half-life.

Posted

Median

Full Range

hour

Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.

Secondary

The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462

AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state calculated by formula amount *time * volume^-1

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD

Secondary

Accumulation Ratio (Racc) of LTT462

Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.

Secondary

Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood

Assessment of Pharmacodynamic (PD) effects of LTT462 in tumor, pre- and post- treatment tumor biopsies were examined for expression of DUSP6. For assessment of PD effects in blood, levels of DUSP6 were measured in blood samples.

The full analysis set included all participants who had received at least one dose of LTT462.

Posted

Mean

Standard Deviation

Ratio

Cycle 1 Days 1, 2, 3, 15 and 16

ID	Title	Description
OG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.
OG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.
OG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.
OG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG0030 affected4 at risk EG0041 affected8 at risk EG0050 affected6 at risk EG0060 affected12 at risk EG0070 affected6 at risk EG0081 affected47 at risk EG0090 affected6 at risk EG0100 affected12 at risk EG0110 affected18 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Retinopathy	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Fatigue	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gait disturbance	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
General physical health deterioration	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Swelling	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Biliary tract infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Peritonitis bacterial	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonia	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sepsis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Blood creatinine increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Glomerulonephritis	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Renal injury	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypotension	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Vena cava thrombosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG0030 affected4 at risk EG0041 affected8 at risk EG0050 affected6 at risk EG0060 affected12 at risk EG0070 affected6 at risk EG0081 affected47 at risk EG0090 affected6 at risk EG0100 affected12 at risk EG0110 affected18 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0012 affected3 at risk EG0023 affected6 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Aortic valve incompetence	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cyanosis	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Tricuspid valve incompetence	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Goitre	Endocrine disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cataract	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Chorioretinopathy	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Corneal disorder	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Cystoid macular oedema	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Detachment of retinal pigment epithelium	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Eye pain	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Macular detachment	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Macular oedema	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Retinal detachment	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Retinal pigment epitheliopathy	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Retinopathy	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vision blurred	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Visual impairment	Eye disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0023 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0013 affected3 at risk EG0022 affected6 at risk EG003
Diverticulum intestinal	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Faeces soft	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0013 affected3 at risk EG0022 affected6 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0023 affected6 at risk EG003
Asthenia	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Face oedema	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Fatigue	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0021 affected6 at risk EG003
General physical health deterioration	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Malaise	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Mucosal dryness	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Mucosal haemorrhage	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Oedema peripheral	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Pain	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Peripheral swelling	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pyrexia	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Swelling	General disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hepatosplenomegaly	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumobilia	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cystitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Device related infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Furuncle	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Influenza	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pneumonia	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash pustular	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Sinusitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Skin infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Tonsillitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Procedural dizziness	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Urostomy complication	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0002 affected2 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Ammonia increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Amylase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0002 affected2 at risk EG0011 affected3 at risk EG0022 affected6 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0013 affected3 at risk EG0020 affected6 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood creatinine increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0022 affected6 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood potassium increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood triglycerides increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood urea increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
C-reactive protein increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Eosinophil count increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gamma-glutamyltransferase	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0021 affected6 at risk EG003
Granulocyte count increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
International normalised ratio increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Lipase	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Lipase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Liver function test	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Platelet count decreased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Troponin increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
White blood cell count increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0023 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperalbuminaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Hyperamylasaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperlipasaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0022 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0021 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0021 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Hypotonia	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Seizure	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Syncope	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Visual field defect	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Delirium	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Depression	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Nephritis	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Genital haemorrhage	Reproductive system and breast disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Prostatic calcification	Reproductive system and breast disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hypertension	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Hypotension	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Pelvic venous thrombosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vena cava thrombosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Venous thrombosis limb	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0000 affected2 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003

ID	Term
D010051	Ovarian Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung
D008545	Melanoma

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
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LTT462 45 mg QD	Participants received 45 mg LTT462 QD as oral capsules.	1	2	1	2	2	2
EG001	LTT462 100 mg QD	Participants received 100 mg LTT462 QD as oral capsules.	0	3	0	3	3	3
EG002	LTT462 150 mg QD	Participants received 150 mg LTT462 QD as oral capsules.	0	6	3	6	6	6
EG003	LTT462 200 mg QD	Participants received 200 mg LTT462 QD as oral capsules.	0	4	1	4	4	4
EG004	LTT462 300 mg QD	Participants received 300 mg LTT462 QD as oral capsules.	2	8	5	8	8	8
EG005	LTT462 400 mg QD	Participants received 400 mg LTT462 QD as oral capsules.	1	6	1	6	6	6
EG006	LTT462 450 mg QD	Participants received 450 mg LTT462 QD as oral capsules.	1	12	8	12	12	12
EG007	LTT462 600 mg QD	Participants received 450 mg LTT462 QD as oral capsules.	1	6	4	6	5	6
EG008	All QD Participants	Participants received 45 to 600 mg LTT462 QD as oral capsules.	6	47	23	47	46	47
EG009	LTT462 150 mg BID	Participants received 150 mg LTT462 BID as oral capsules.	1	6	3	6	6	6
EG010	LTT462 200 mg BID	Participants received 200 mg LTT462 BID as oral capsules.	0	12	5	12	12	12
EG011	All BID Participants	Participants received 150 and 200 mg LTT462 BID as oral capsules.	1	18	8	18	18	18