Study of MLN2480 in Participants With Relapsed or Refract... | NCT01425008

ID	Type	Description
2012-003397-16	EudraCT Number
U1111-1164-7508	Registry Identifier	WHO
13/SC/0007	Registry Identifier	NRES

Label	Type	Description	Intervention Names
MLN2480	Experimental		Drug: MLN2480

Name	Type	Description	Arm Group Labels	Other Names
MLN2480	Drug	Dose Escalation Phase: participants will receive MLN2480 orally in escalating doses every other day or once weekly for three weeks of a 28-day cycle. Participants may continue treatment for additional cycles (up to 12 months) until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. If it is determined that a participant would derive benefit from continued therapy beyond 12 months treatment may continue. Dose Expansion Phase: Participants will take MLN2480 at the maximum tolerated dose orally every other day or once weekly for three weeks of a 28-day cycle until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. The maximum duration of treatment is 1 year unless determined that a participant would derive benefit from continued therapy beyond 12 months.

Measure	Description	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths		Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)
Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)	Dose limiting AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Dose limiting AEs were defined as any of the following events: Grade 4 neutropenia for more than 7 days under maximum supportive therapy; febrile neutropenia; platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; if Course 2 was not initiated within 14 days due to AE related to the protocol treatment; Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (example, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.	Cycle 1 (Cycle length= 22 days [Q2D] and 28 days [QW])
Number of Participants With TEAEs Related to Physical Examination Findings		Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)
Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)		Baseline up to EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings

Measure	Description	Time Frame
Overall Response Rate (ORR)	ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). The ORR assessment was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30% decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.

Name	Affiliation	Role
Medical Monitor	Millennium Pharmaceuticals, Inc.	Study Director

PubMed Identifier	Type	Citation	Retractions
37219686	Derived	Rasco DW, Medina T, Corrie P, Pavlick AC, Middleton MR, Lorigan P, Hebert C, Plummer R, Larkin J, Agarwala SS, Daud AI, Qiu J, Bozon V, Kneissl M, Barry E, Olszanski AJ. Phase 1 study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2023 Jul;92(1):15-28. doi: 10.1007/s00280-023-04544-5. Epub 2023 May 23.

ID	Title	Description
FG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 milligram (mg), tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
FG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jul 29, 2016	Oct 16, 2019

Arm/Group Information

ID	Title	Description
BG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG003	Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	TAK-580 135 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG004	Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	TAK-580 200 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG005	Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	TAK-580 280 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG006	Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG007	QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	TAK-580 400 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG008	QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG009	QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	TAK-580 800 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
BG010	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
BG011	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, which in response to previous treatment with RAF inhibitors and/or MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.
BG012	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
BG013	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, which in response to previous treatment with MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.
BG014	Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative cutaneous melanoma (WT), naive to any prior anticancer therapy except ipilimumab, PD-1, and PDL-1 monoclonal antibodies.
BG015	Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative melanoma (WT), who had received at least 1 line of prior anticancer therapy.
BG016	Q2D Dose Expansion Phase: Pharmacokinetic Cohort	TAK-580 200 mg, tablets, orally, on Days 1 through 21 in a 28-days treatment Cycle 1, followed by TAK-580 200 mg, tablets, orally, Q2D in each 28-days treatment cycle from Cycle 2 until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with any advanced solid tumor (excluding lymphoma, but including melanoma) who had failed or were not candidates for standard therapies or for whom no approved therapy was available.
BG017	Q2D Dose Expansion Phase: TAK-580 (BRAF+)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF-mutation positive cutaneous melanoma.
BG018	QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49), in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
BG019	Total	Total of all reporting groups

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

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths

The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose, or start of subsequent therapy, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle=22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle=28 days] in Expansion Phase)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG003	Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	TAK-580 135 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG004	Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	TAK-580 200 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG005	Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	TAK-580 280 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG006	Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG007	QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	TAK-580 400 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG008	QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG009	QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	TAK-580 800 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG010	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
OG011	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, which in response to previous treatment with RAF inhibitors and/or MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.
OG012	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
OG013	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, which in response to previous treatment with MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.
OG014	Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative cutaneous melanoma (WT), naive to any prior anticancer therapy except ipilimumab, PD-1, and PDL-1 monoclonal antibodies.
OG015	Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative melanoma (WT), who had received at least 1 line of prior anticancer therapy.
OG016	Q2D Dose Expansion Phase: Pharmacokinetic Cohort	TAK-580 200 mg, tablets, orally, on Days 1 through 21 in a 28-days treatment Cycle 1, followed by TAK-580 200 mg, tablets, orally, Q2D in each 28-days treatment cycle from Cycle 2 until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with any advanced solid tumor (excluding lymphoma, but including melanoma) who had failed or were not candidates for standard therapies or for whom no approved therapy was available.
OG017	QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49), in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
OG018	Q2D Dose Expansion Phase: TAK-580 (BRAF+)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF-mutation positive cutaneous melanoma.

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0004 OG0013 OG0023 OG003

Primary

Dose Escalation Phase: Number of Participants With Dose-limiting Adverse Events (AEs)

Dose limiting AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Dose limiting AEs were defined as any of the following events: Grade 4 neutropenia for more than 7 days under maximum supportive therapy; febrile neutropenia; platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; if Course 2 was not initiated within 14 days due to AE related to the protocol treatment; Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (example, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.

The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Posted

Count of Participants

Participants

Cycle 1 (Cycle length= 22 days [Q2D] and 28 days [QW])

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)

Primary

Number of Participants With TEAEs Related to Physical Examination Findings

The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Posted

Count of Participants

Participants

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Primary

Clinically Significant Change From Baseline in Body Weight at End of Study Visit (EOSV)

The safety population included all participants who received at least 1 dose of study drug (TAK-580). Participants who were evaluable for this measure at given time point were included for the assessment.

Posted

Mean

Standard Deviation

kilogram (kg)

Baseline up to EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Primary

Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings

The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Posted

Count of Participants

Participants

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Primary

Eastern Cooperative Oncology Group (ECOG) Performance Score

ECOG performance score was measured on 6 point scale to assess participant's performance status, where: 0 (fully active, able to carry on all pre-disease activities without restriction); 1 (restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work); 2 (ambulatory greater than(>) 50 percent (%) of waking hours), capable of all self-care, unable to carry out any work activities); 3 (capable of only limited self-care, confined to bed or chair >50% of waking hours); 4(completely disabled, cannot carry on any self-care, totally confined to bed or chair); 5 (dead). A higher score indicated greater functional impairment.

Posted

Mean

Standard Deviation

score on a scale

at EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)

Primary

Number of Participants With TEAEs Categorized Into Investigations Related to Laboratory Test of Chemistry, Hematology or Urinalysis

The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Posted

Count of Participants

Participants

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Overall Response Rate (ORR)

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR). The ORR assessment was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30% decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.

Response-evaluable population included all participants with measurable disease who received any amount of TAK-580 and had at least 1 postbaseline response assessment.

Posted

Number

percentage of participants

Baseline up to EOSV (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle length =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle length =28 days] in Expansion Phase)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Progression-free Survival (PFS)

PFS was the time from first dose date of study drug to date of the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. The PFS assessment was based on RECIST 1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval. Participants with no response assessment were censored at the date of first dose.

The safety population included all participants who received at least 1 dose of study drug (TAK-580).

Posted

Median

95% Confidence Interval

months

Baseline up to the date of first document PD, or death due to any cause, whichever occurred first (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle =28 days] in Expansion Phase)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Duration of Response (DOR)

DOR was assessed from the first documented response (CR or PR) to the date of first documented PD and was censored at the date of the last assessment for responders who died without documented PD and for responders who were still alive and had not progressed. DOR assessment was based on RECIST v1.1. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. DOR was calculated using Kaplan-Meier estimate.

Analysis population included only a subset of participants (all responders) with response.

Posted

Median

95% Confidence Interval

months

From the first documented response (CR or PR) up to the date of first documented PD (up to Cycle 38 Days 52 [Q2D] and 58 [QW] [Cycle =22 days (Q2D) and 28 days (QW)] in Escalation Phase; Cycle 49 Day 58 [Cycle =28 days] in Expansion Phase)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-580

The PK-evaluable population included all participants who had sufficient dosing data and TAK-580 concentration-time data to permit calculation of any TAK-580 parameters. PK-evaluable population where data at specified time points was available.

Posted

Geometric Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Escalation (Esc.) and Expansion (Exp.) Q2D: C1D1 and 21 pre-dose and at multiple time points (up to 48 hours [h]) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D1 and 22 at multiple time-points (up to168 h) post-dose (C=28 days)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Ctrough: Trough Concentration for TAK-580

Posted

Mean

Standard Deviation

ng/mL

Escalation and Expansion Q2D Cohorts: C1D21 pre-dose (C=22 days [Escalation Q2D] and 28 days [Expansion Q2D]); Escalation QW Cohorts: C1D22 pre-dose (C= 28 days)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, Tmax: Time to Reach the Cmax for TAK-580

Posted

Median

Full Range

hour

Escalation (Esc.) and Expansion (Exp.) Q2D: C1D1 and 21 pre-dose and at multiple time points (up to 48 h) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D1 and 22 at multiple time-points (up to168 h) post-dose (C=28 days)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, t1/2z: Terminal Phase Disposition Half-life for TAK-580

PK-evaluable population. t1/2z of TAK-580 could not be determined in cancer participants who were on Q2D regimen with a 48-hour dose interval since the duration of plasma PK sample collection within the dose interval was shorter than the anticipated t1/2z of TAK-580. PK-evaluable population where data at specified time points was available.

Posted

Median

Full Range

hour

Escalation (Esc.) and Expansion (Exp.) Q2D: C1D21 pre-dose and at multiple time points (up to 48 h) post-dose (C=22 days [Esc. Q2D] and 28 days [Exp. Q2D]); Esc. QW: C1D22 at multiple time-points (up to168 h) post-dose (C=28 days)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)

Secondary

Dose Escalation Phase and Dose Expansion Pharmacokinetic Cohort, CLr: Renal Clearance for TAK-580

CLr of TAK-580 could not be determined since urine samples were collected for a limited duration during a site visit.

Posted

Q2D Cohorts: Cycle1 Days 1 and 21 up to 24 hours post-dose (Cycle1 length= 22 days); QW Cohorts: Cycle2 Days 1 and 22 up to 7 hours post-dose (Cycle 2 length= 28 days)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Q2D Dose Escalation Phase and Q2D Dose Expansion Pharmacokinetic Cohort, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-580

Posted

Mean

Standard Deviation

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

Cycle 1 Days 1 and 21 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 22 days)

ID	Title	Description
OG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablet, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

QW Dose Escalation Phase, AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for TAK-580

Posted

Mean

Standard Deviation

h*ng/mL

Cycle 1 Days 1 and 22 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length= 28 days)

ID	Title	Description
OG000	QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	TAK-580 400 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG001	QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).
OG002	QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	TAK-580 800 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).

Secondary

Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in RAF Inhibition Biomarkers at Specified Time Points

The extent of phosphorylated extracellular signal-regulated kinase (pERK) staining was assessed in the melanoma expansion cohorts. The level of staining was assessed by a pathologist (semi-H scores) and by quantified image analysis (quant H-scores). The H-score scale used to interpret data from the pathologist rating was as follows: 0 to 99 =low staining; 100 to 199= medium staining; 200 to 300 =high staining. The H-score scale used to interpret data from the quantified image analysis was as followed: 0 to 100 =low staining; 100 to 150= medium staining; 150 to 235= high staining.

Pharmacodynamic (PD)-evaluable: all participants who had sufficient dosing and PD data,collected within protocol-specified window of sampling time.Participants who were evaluable for this measure at given time point were included. Data for this measure was not planned to be collected and analyzed for Q2D Dose Expansion Phase:Pharmacokinetic Cohort.

Posted

Median

Full Range

percent change

Baseline, Cycle 1 Day 21 (Q2D), and Cycle 1 Day 22 (QW) (Cycle length= 22 days [Q2D] and 28 days [QW])

ID	Title	Description
OG000	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.
OG001

Secondary

Dose Expansion Phase, Melanoma Cohorts: Percent Change From Baseline in Apoptotic Biomarkers at Specified Time Points

The extent of cleaved poly ADP-ribose polymerase (cPARP) and BIM-1 was assessed in the melanoma expansion cohorts. The level of staining was assessed by quantified image analysis (quant H-scores) and by quantified image analysis (quant H-scores). The H-score scale used to interpret data from the pathologist rating was as follows: 0 to 99= low staining; 100 to 199 =medium staining; 200 to 300 =high staining. The H-score scale used to interpret data from the quantified image analysis was as followed in cPARP: 0 to 70= low staining; 70 to 175 =medium staining; 175 to 240 =high staining; BIM-1: 0 to 128= low staining; 128 to 155 =medium staining; 155 to 229 =high staining.

PD-evaluable: all participants who had sufficient dosing and PD data, collected within protocol-specified window of sampling time. Participants who were evaluable for this measure at given time point were included. Data for this measure was not planned to be collected and analyzed for Q2D Dose Expansion Phase: Pharmacokinetic Cohort.

Posted

Median

Full Range

percent change

Baseline, Cycle 1 Day 21 (Q2D), and Cycle 1 Day 22 (QW) (Cycle length= 22 days [Q2D] and 28 days [QW])

ID	Title	Description
OG000	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Q2D Dose Escalation Phase: TAK-580 20 mg (22 Days Cycle)	TAK-580 20 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cy cle 38).	1	4	2	4	4	4
EG001	Q2D Dose Escalation Phase: TAK-580 40 mg (22 Days Cycle)	TAK-580 40 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	0	3	0	3	3	3
EG002	Q2D Dose Escalation Phase: TAK-580 80 mg (22 Days Cycle)	TAK-580 80 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	1	3	1	3	3	3
EG003	Q2D Dose Escalation Phase: TAK-580 135 mg (22 Days Cycle)	TAK-580 135 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	0	3	0	3	3	3
EG004	Q2D Dose Escalation Phase: TAK-580 200 mg (22 Days Cycle)	TAK-580 200 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	0	7	2	7	7	7
EG005	Q2D Dose Escalation Phase: TAK-580 280 mg (22 Days Cycle)	TAK-580 280 mg, tablets, orally, Q2D, in each 22-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	1	7	4	7	7	7
EG006	Q2D Dose Escalation Phase: TAK-580 200 mg (28 Days Cycle)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	0	3	1	3	3	3
EG007	QW Dose Escalation Phase: TAK-580 400 mg (28 Days Cycle)	TAK-580 400 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	0	3	2	3	3	3
EG008	QW Dose Escalation Phase: TAK-580 600 mg (28 Days Cycle)	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	2	13	5	13	12	13
EG009	QW Dose Escalation Phase: TAK-580 800 mg (28 Days Cycle)	TAK-580 800 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 38).	1	4	3	4	4	4
EG010	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.	0	16	9	16	16	16
EG011	Q2D Dose Expansion Phase: TAK-580 (BRAF+ Previously Treated)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF mutation-positive cutaneous melanoma, which in response to previous treatment with RAF inhibitors and/or MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.	2	8	6	8	8	8
EG012	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Naive)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.	2	16	5	16	16	16
EG013	Q2D Dose Expansion Phase: TAK-580 (NRAS+ Previously Treated)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with NRAS mutation-positive cutaneous melanoma, which in response to previous treatment with MEK inhibitors had relapsed following an objective response, failed to demonstrate an objective response and/or could not tolerate such a regimen due to unacceptable toxicity.	0	1	1	1	1	1
EG014	Q2D Dose Expansion Phase: TAK-580 BRAF/NRAS WT+ Naive	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative cutaneous melanoma (WT), naive to any prior anticancer therapy except ipilimumab, PD-1, and PDL-1 monoclonal antibodies.	0	6	2	6	6	6
EG015	Q2D Dose Expansion Phase:TAK-580 BRAF/NRASWT+PreviouslyTreated	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF/NRAS mutation-negative melanoma (WT), who had received at least 1 line of prior anticancer therapy.	0	11	4	11	11	11
EG016	Q2D Dose Expansion Phase: Pharmacokinetic Cohort	TAK-580 200 mg, tablets, orally, on Days 1 through 21 in a 28-days treatment Cycle 1, followed by TAK-580 200 mg, tablets, orally, Q2D in each 28-days treatment cycle from Cycle 2 until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with any advanced solid tumor (excluding lymphoma, but including melanoma) who had failed or were not candidates for standard therapies or for whom no approved therapy was available.	1	20	11	20	19	20
EG017	Q2D Dose Expansion Phase: TAK-580 (BRAF+)	TAK-580 200 mg, tablets, orally, Q2D, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49) in participants with BRAF-mutation positive cutaneous melanoma.	1	2	2	2	2	2
EG018	QW Dose Expansion Phase: TAK-580 NRAS WT+ Naive	TAK-580 600 mg, tablets, orally, QW, in each 28-days treatment cycle until disease progression, unacceptable toxicity, or participant discontinuation for any other reason (up to Cycle 49), in participants with NRAS mutation-positive cutaneous melanoma, naive to prior therapy with RAF and MEK inhibitors.	0	19	8	19	19	19

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG0030 events0 affected3 at risk EG004
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Diverticular perforation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Retroperitoneal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumonia	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Sepsis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Escherichia sepsis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Metastatic malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Colon cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Asthenia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Peripheral swelling	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Adverse drug reaction	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Guillain-Barre syndrome	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ataxia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ejection fraction decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG0033 events3 affected3 at risk EG0043 events3 affected7 at risk EG0052 events2 affected7 at risk EG0060 events0 affected3 at risk EG0070 events0 affected3 at risk EG0084 events4 affected13 at risk EG0090 events0 affected4 at risk EG01042 events12 affected16 at risk EG01123 events7 affected8 at risk EG01211 events9 affected16 at risk EG0130 events0 affected1 at risk EG0143 events3 affected6 at risk EG0151 events1 affected11 at risk EG01610 events6 affected20 at risk EG0170 events0 affected2 at risk EG0185 events4 affected19 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Retching	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lip swelling	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Chapped lips	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Glossodynia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Lip dry	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Salivary gland pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Fatigue	General disorders	MedDRA (19.0)	Systematic Assessment	EG0003 events3 affected4 at risk EG0011 events1 affected3 at risk EG0021 events1 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0023 events2 affected3 at risk EG003
Pyrexia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Face oedema	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Chills	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Chest pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Mucosal inflammation	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Influenza like illness	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Peripheral swelling	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Chest discomfort	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Localised oedema	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Oedema	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Asthenia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Axillary pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Catheter site pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Facial pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Feeling cold	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gait disturbance	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Injection site bruising	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Malaise	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Swelling face	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Madarosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Butterfly rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypertrichosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lichenoid keratosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Livedo reticularis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin plaque	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0003 events2 affected4 at risk EG0012 events2 affected3 at risk EG0020 events0 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Weight decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood creatinine increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood calcium decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haemoglobin decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Weight increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood phosphorus decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
White blood cell count decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood sodium decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood folate decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood potassium increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Breath sounds abnormal	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Electrocardiogram T wave inversion	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
International normalised ratio increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lipase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neutrophil count increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
White blood cell count increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ageusia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Presyncope	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Aphasia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ataxia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Balance disorder	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dysarthria	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Facial paralysis	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperaesthesia	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lethargy	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Memory impairment	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nervous system disorder	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Poor quality sleep	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Somnolence	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tremor	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nasal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nasal ulcer	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Restrictive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Throat tightness	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0023 events2 affected3 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Fluid retention	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Reticulocytosis	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cellulitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumonia	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Sepsis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lung infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Oral herpes	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Candida infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Escherichia urinary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rash pustular	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Rhinitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Sinusitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tinea infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Biliary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Bronchitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ear lobe infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Folliculitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Genital infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Klebsiella bacteraemia	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Laryngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Paronychia	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Peritonitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Post procedural infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Periorbital oedema	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eye swelling	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vision blurred	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eye pain	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dry eye	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eye haemorrhage	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eyelash discolouration	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lacrimation increased	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eye irritation	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eye pruritus	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eyelid disorder	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eyelid irritation	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eyelids pruritus	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Optic nerve disorder	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Photophobia	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Scleral haemorrhage	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vitreous floaters	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Flushing	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hot flush	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypertension	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haematoma	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lymphoedema	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Peripheral coldness	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Raynaud's phenomenon	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vena cava thrombosis	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ureteric obstruction	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Urinary bladder haemorrhage	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Palpitations	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Depression	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hallucination	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Mood altered	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Conjunctival abrasion	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Stoma site pain	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0003 events2 affected4 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Metastases to chest wall	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cerumen impaction	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ear disorder	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Motion sickness	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Atrophic vulvovaginitis	Reproductive system and breast disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Breast oedema	Reproductive system and breast disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Scrotal oedema	Reproductive system and breast disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (19.0)	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		San Francisco	California		United States

ID	Term
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
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases