E7050 in Combination With Sorafenib Versus Sorafenib Alon... | NCT01271504

ID	Type	Description	Link
2011-000752-41	EudraCT Number

Name	Class
PharmaBio Development Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Phase Ib: Cohort 1,2, and 3	Active Comparator	Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib	Drug: Sorafenib
Phase II: Arm 1; E7050 + Sorafenib	Active Comparator	Phase II: Arm 1; E7050 + 400 mg Sorafenib Arm 2; 400 mg Sorafenib	Drug: Sorafenib

Name	Type	Description	Arm Group Labels	Other Names
Sorafenib	Drug	Phase Ib: Cohort 1; 200 mg E7050 + 400 mg Sorafenib Cohort 2; 300 mg E7050 + 400 mg Sorafenib Cohort 3; 400 mg E7050 + Sorafenib	Phase Ib: Cohort 1,2, and 3

Measure	Description	Time Frame
Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)	DLTs were defined as clinically significant adverse events (AEs) (non-hematological, hematological and other events) occurring less than or equal to (<=) 28 days after commencing study treatment and considered to be at least possibly or probably related to study drug by the Investigator. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v.4.0).	Cycle 1 (Cycle length is 28 days)
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day -7		Day -7: 0-72 hours post-dose
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1		Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1		Cycle 1 Day 28: 0-24 hours post-dose
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day -7		Day -7: 0-72 hours post-dose
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1		Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)
Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1

Measure	Description	Time Frame
Phase 2: Time to Progression (TTP)	TTP was defined as the time from the date of randomization until the date of PD of such participants disease based on independent assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PD was defined as at least a 20% increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan-Meier (K-M) method.

Name	Affiliation	Role
Melissa J Versola, RN	Quintiles, Inc.	Study Director

ID	Title	Description
FG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 milligram (mg), tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 Days).

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

Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)

DLTs were defined as clinically significant adverse events (AEs) (non-hematological, hematological and other events) occurring less than or equal to (<=) 28 days after commencing study treatment and considered to be at least possibly or probably related to study drug by the Investigator. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v.4.0).

Safety analysis set included all participants enrolled and randomized into the Phase 1b of this study, except those who dropped out of the study prior to receiving any study drug, or were without any safety assessment after first dose of study drug.

Posted

Count of Participants

Participants

Cycle 1 (Cycle length is 28 days)

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 Days).
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 Days).

Units	Counts
Participants	OG0007 OG0017

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0012

Primary

Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day -7

Pharmacokinetic (PK) analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

Day -7: 0-72 hours post-dose

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.

Units	Counts
Participants	OG000

Primary

Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice on Day 1 of Cycle 1.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice on Day 1 of Cycle 1.

Units	Counts
Participants	OG000

Primary

Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters. Here, overall number analyzed "N" were the participants who were evaluable for the outcome measure.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 28: 0-24 hours post-dose

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily from Day 1 to 28 of Cycle 1.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily from Day 1 to 28 of Cycle 1.

Units	Counts
Participants	OG000

Primary

Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day -7

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Median

Full Range

hour

Day -7: 0-72 hours post-dose

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.

Units	Counts
Participants	OG000

Primary

Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Median

Full Range

hour

Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice on Day 1 of Cycle 1.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice on Day 1 of Cycle 1.

Units	Counts
Participants	OG000

Primary

Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1

Posted

Median

Full Range

hour

Cycle 1 Day 28: 0-24 hours post-dose

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily from Day 1 to 28 of Cycle 1.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily from Day 1 to 28 of Cycle 1.

Units	Counts
Participants	OG000

Primary

Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day -7

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Mean

Standard Deviation

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

Day -7: 0-72 hours post-dose

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.

Units	Counts
Participants	OG000

Primary

Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Mean

Standard Deviation

ng*h/mL

Cycle 1 Day 1: 0-24 hours post-dose (Cycle length is 28 days)

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice on Day 1 of Cycle 1.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice on Day 1 of Cycle 1.

Units	Counts
Participants	OG000

Primary

Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1

Posted

Mean

Standard Deviation

ng*h/mL

Cycle 1 Day 28: 0-24 hours post-dose (Cycle length is 28 days)

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily from Day 1 to 28 of Cycle 1.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily from Day 1 to 28 of Cycle 1.

Units	Counts
Participants

Primary

Phase 1b: t1/2: Terminal Elimination Half-life for Golvatinib When Administered in Combination With Sorafenib at Day -7

PK analysis set was defined as all participants in the safety population who had sufficient concentration data to derive one or more of the PK parameters.

Posted

Mean

Standard Deviation

hour

Day -7: 0-72 hours post-dose

ID	Title	Description
OG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.
OG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once in combination with sorafenib 400 mg, tablet, orally twice on Day-7.

Units	Counts
Participants	OG000

Primary

Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Safety analysis set included all participants enrolled and randomized to treatment in the Phase 2 of this study, except for those who dropped out prior to receiving any study drug, or were without any safety assessment following the first dose of study drug.

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).

Units

Primary

Phase 2: Number of Participants With AEs by Severity Grades

AE severity was graded using CTCAE version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Higher grade indicates more severe condition.

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).

Primary

Phase 2: Number of Participants With Adverse Events Related to Vital Signs

Number of participants are reported with AEs related to Vital signs including body temperature, respiratory rate, heart rate, height, and weight.

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).

Primary

Phase 2: Number of Participants With Clinically Significant Change From Baseline in Blood Pressure Including Systolic and Diastolic Blood Pressures

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).

Primary

Phase 2: Number of Participants With Worst Shifts Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)

Number of participants with worst shifts post baseline in ECOG-PS levels were reported. ECOG has 6 levels (0-5). Level 0 is the best status (fully active, able to carry on all pre-disease performance without restriction); Level 1 is mildly restricted (Restricted in physically strenuous activity but ambulatory ad able to carry out work of a light or sedentary nature, e.g. light house work, office work); Level 2 is more restricted (Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours); Level 3 is restricted (Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours); Level 4 is highly restricted (completely disabled; cannot carry on any selfcare; totally confined to bed or chair); and Level 5 is death (dead).

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).

Primary

Phase 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).

Units

Primary

Phase 2: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).

Units

Secondary

Phase 2: Time to Progression (TTP)

TTP was defined as the time from the date of randomization until the date of PD of such participants disease based on independent assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PD was defined as at least a 20% increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan-Meier (K-M) method.

Modified Intent-to-Treat (MITT) set included all participants randomized in the applicable study arm, except a participant who dropped out of such arm prior to receiving any comparator or investigative drug. Here 'N' (Overall number of participants analyzed) signifies participants with events (PD).

Posted

Median

99% Confidence Interval

weeks

From the date of randomization until the date of PD (up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).
OG001	Phase 2: Sorafenib 400 mg

Secondary

Phase 2: Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization of a participant until (1) the date of first documented progression (2) the date of such participant's death due to any cause based on independent assessments according to RECIST v. 1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using KM method.

MITT analysis set included all participants randomized in the applicable study arm, except a participant who dropped out of such arm prior to receiving any comparator or investigative drug. Here 'N' (Overall number of participants analyzed) signifies participants with events (PD or/and death).

Posted

Median

95% Confidence Interval

weeks

From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).
OG001	Phase 2: Sorafenib 400 mg

Secondary

Phase 2: Percentage of Participants With PFS at Week 12

The PFS rate at week 12 was defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS was defined as the time from the date of randomization of a participant until (1) the date of first documented progression (2) the date of such participant's death due to any cause based on independent assessments according to RECIST v. 1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

Posted

Number

percentage of participants

At 12 weeks

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
OG001	Phase 2: Sorafenib 400 mg

Secondary

Phase 2: Overall Survival (OS)

OS was defined as the time from the date of randomization until the date of death. Participants were censored at the date of last known alive. OS was analyzed using K-M method.

MITT analysis set included all participants randomized in the applicable study arm, except a participant who dropped out of such arm prior to receiving any comparator or investigative drug.

Posted

Median

95% Confidence Interval

weeks

From the date of randomization until the date of death (Up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).
OG001	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).

Secondary

Phase 2: Percentage of Participants With Overall Response

Overall response rate was defined as percentage of participants with best confirmed response (CR) or partial response (PR) assessed by investigator per RECIST v1.1. A confirmatory scan was required after no less than 4 weeks and no later than 8 weeks, starting on the date that the response was first recorded. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<)10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

MITT analysis set included all participants randomized in the applicable study arm, except a participant who dropped out of such arm prior to receiving any comparator or investigative drug.

Posted

Number

95% Confidence Interval

percentage of participant

From the date of randomization until disease progression or death (Up to approximately 3 years 11 months)

ID	Title	Description
OG000	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).
OG001	Phase 2: Sorafenib 400 mg

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG0030 affected42 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Transaminases Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Metabolic Encephalopathy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Confusional State	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Nephropathy Toxic	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Dermatitis Acneiform	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Dermatitis Psoriasiform	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Cardiac Arrest	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Abdominal Distension	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Diverticular Perforation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Gastric Ulcer	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Oesophageal Varices Haemorrhage	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Pancreatitis Acute	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
General Physical Health Deterioration	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Non-Cardiac Chest Pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Oedema Peripheral	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hepatic Failure	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Liver Disorder	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Escherichia Urinary Tract Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Infected Skin Ulcer	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Infective Exacerbation Of Chronic Obstructive Airways Disease	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Klebsiella Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Liver Abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Pneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Scrotal Abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Sepsis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0023 affected42 at risk EG003
Septic Shock	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Adenocarcinoma Gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Malignant Neoplasm Progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Ataxia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hepatic Encephalopathy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Ischaemic Stroke	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Renal Impairment	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Palmar-Plantar Erythrodysaesthesia Syndrome	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Aneurysm Ruptured	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hypertensive Crisis	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hypotension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Renal Failure	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0016 affected7 at risk EG00226 affected42 at risk EG00322 affected42 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0006 affected7 at risk EG0015 affected7 at risk EG00215 affected42 at risk EG003
Fatigue	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0014 affected7 at risk EG00213 affected42 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0015 affected7 at risk EG00211 affected42 at risk EG003
Asthenia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG00212 affected42 at risk EG003
Palmar-Plantar Erythrodysaesthesia Syndrome	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0013 affected7 at risk EG00215 affected42 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG00213 affected42 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0015 affected7 at risk EG00214 affected42 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0015 affected7 at risk EG0028 affected42 at risk EG003
Blood Alkaline Phosphatase Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0003 affected7 at risk EG0014 affected7 at risk EG0026 affected42 at risk EG003
Hypertension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0028 affected42 at risk EG003
Alanine Aminotransferase Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0014 affected7 at risk EG0027 affected42 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0028 affected42 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0028 affected42 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected7 at risk EG0011 affected7 at risk EG0027 affected42 at risk EG003
Headache	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0013 affected7 at risk EG0028 affected42 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0029 affected42 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected7 at risk EG0026 affected42 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0014 affected7 at risk EG0025 affected42 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0028 affected42 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected7 at risk EG0024 affected42 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0012 affected7 at risk EG0021 affected42 at risk EG003
Anaemia Macrocytic	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG003
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected7 at risk EG0021 affected42 at risk EG003
Abdominal Discomfort	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Anal Fissure	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Anorectal Discomfort	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0025 affected42 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hypoaesthesia Oral	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0026 affected42 at risk EG003
Leukopenia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected7 at risk EG0020 affected42 at risk EG003
Dry Eye	Eye disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0022 affected42 at risk EG003
Vision Blurred	Eye disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Oedema Peripheral	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0013 affected7 at risk EG0025 affected42 at risk EG003
Mucosal Inflammation	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG003
Pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Chills	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Oedema	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Vessel Puncture Site Bruise	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Drug Hypersensitivity	Immune system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected7 at risk EG0022 affected42 at risk EG003
Bronchitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Oesophageal Candidiasis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Pneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Blood Creatinine Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0003 affected7 at risk EG0012 affected7 at risk EG0021 affected42 at risk EG003
Blood Bilirubin Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0003 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG003
Lipase Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected7 at risk EG0021 affected42 at risk EG003
Ammonia Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Amylase Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Blood Lactate Dehydrogenase Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Blood Thyroid Stimulating Hormone Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Heart Rate Increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Platelet Count Decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Weight Decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected7 at risk EG0014 affected7 at risk EG0021 affected42 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected7 at risk EG0014 affected7 at risk EG0023 affected42 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0014 affected7 at risk EG0023 affected42 at risk EG003
Decreased Appetite	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected7 at risk EG00213 affected42 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0012 affected7 at risk EG0022 affected42 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0012 affected7 at risk EG0022 affected42 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0012 affected7 at risk EG0022 affected42 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0013 affected7 at risk EG0024 affected42 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected7 at risk EG0020 affected42 at risk EG003
Fluid Overload	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hypervolaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
hypoproteinaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG003
Neck Pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected7 at risk EG0020 affected42 at risk EG003
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG003
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0022 affected42 at risk EG003
Dizziness	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Dementia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0024 affected42 at risk EG003
Hepatic Encephalopathy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Memory Impairment	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Neuropathy Peripheral	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Restless Legs Syndrome	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0013 affected7 at risk EG0021 affected42 at risk EG003
Agitation	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0025 affected42 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0012 affected7 at risk EG0021 affected42 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Renal Failure Chronic	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Urinary Incontinence	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Vaginal Haemorrhage	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Vaginal Polyp	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Vulvovaginal Discomfort	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0022 affected42 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Throat tightness	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected7 at risk EG0022 affected42 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Dermatitis psoriasiform	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0021 affected42 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Hot flush	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected7 at risk EG0020 affected42 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0023 affected42 at risk EG003
Lethargy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0023 affected42 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Depression	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Malaise	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Transaminases increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Haematoma	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hyperlipasaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Liver disorder	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Plantar erythema	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Protein urine present	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Acid fast bacilli infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Acidosis	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Aphonia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Axillary mass	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Bacterial test positive	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Balance disorder	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Blood albumin decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Blood potassium increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Blood urine present	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Body temperature increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Breath sounds abnormal	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Cystitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Diabetic ulcer	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Ear pruritus	Ear and labyrinth disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Early satiety	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
External ear inflammation	Ear and labyrinth disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Face oedema	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Facial pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Faecal incontinence	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Faeces soft	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Flushing	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Food poisoning	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Gastric hypomotility	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Genital lesion	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Globulins increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Glossitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hepatic pain	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hypothermia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Inflammation	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Influenza	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Influenza like illness	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Injection site haematoma	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Lip blister	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Liver tenderness	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Localised infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Localised oedema	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Malabsorption	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Malnutrition	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Mental impairment	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Monoparesis	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Myositis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Nipple pain	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Pallor	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Prostatic obstruction	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Retching	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Serum ferritin increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Sinusitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Somnolence	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Subcutaneous haematoma	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Syncope	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Tenosynovitis stenosans	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Testicular pain	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Testicular swelling	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Thirst	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Thyroxine increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Tooth abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Urine analysis abnormal	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Vascular insufficiency	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Viral diarrhoea	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Xerosis	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Eye pain	Eye disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Pyrexia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected7 at risk EG0023 affected42 at risk EG003
Weight Decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0026 affected42 at risk EG003
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0023 affected42 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected7 at risk EG0014 affected7 at risk EG0021 affected42 at risk EG003
Hypotension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Dyspnoea Exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Abdominal Pain Lower	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Chest Pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Eye Contusion	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Fungal Skin Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0021 affected42 at risk EG003
Gastroenteritis Viral	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Generalised Oedema	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Hepatitis C Virus Test Positive	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Liver Palpable Subcostal	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0020 affected42 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected7 at risk EG0022 affected42 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected7 at risk EG0020 affected42 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Tucson	Arizona	85715	United States

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases

ID	Term
D010671	Phenylurea Compounds
D014508	Urea
D000577	Amides
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009536	Niacinamide
D009539	Nicotinic Acids
D000147	Acids, Heterocyclic
D006571	Heterocyclic Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description
BG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 Days).
BG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 Days).
BG002	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).
BG003	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 Days).
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1b: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 days).	7	7	4	7	7	7
EG001	Phase 1b: Golvatinib 300 mg + Sorafenib 400 mg	Participants received golvatinib 300 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 513 days).	6	7	3	7	6	7
EG002	Phase 2: Golvatinib 200 mg + Sorafenib 400 mg	Participants received golvatinib 200 mg, tablet, orally, once daily in combination with sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).	32	42	20	42	40	42
EG003	Phase 2: Sorafenib 400 mg	Participants received sorafenib 400 mg, tablet, orally, twice daily in 28-days treatment cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first (Up to 705 days).	32	42	17	42	40	42