A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in P... | NCT01107418

Label	Type	Intervention Names
1	Experimental	Drug: RO5185426
2	Experimental	Drug: RO5185426
3	Experimental	Drug: RO5185426
4	Experimental	Drug: RO5185426

Name	Type	Description	Arm Group Labels	Other Names
RO5185426	Drug	dosage b) orally twice daily, days 1-15 (morning dose)	2

Measure	Description	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15

Measure	Description	Time Frame
Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)	Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		La Jolla	California	92093	United States

PubMed Identifier	Type	Citation	Retractions
24983357	Derived	Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.
23457002

ID	Title	Description
FG000	Vemurafenib - All Cohorts	Participants received vemurafenib (RO5185426) film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 milligrams (mg) on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

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

Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1

Pharmacokinetic (PK) population included all participants who provided essential PK data up to and including the pre-dose PK sample taken on Cycle 1, Day 22, without major protocol violation.

Posted

Mean

Standard Deviation

micrograms*hour/milliliter (mcg*h/mL)

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG003	Cohort 4 - Vemurafenib 960 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Units	Counts
Participants	OG00012 OG00112 OG00212 OG003

Title

Denominators

Categories

Title	Measurements
	OG0008.3± 6.13 OG00113.8± 7.72 OG00221.9± 12.97 OG003

Primary

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg*h/mL

Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1

PK population.

Posted

Mean

Standard Deviation

micrograms/milliliter (mcg/mL)

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1

PK population.

Posted

Median

Full Range

hours

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg*h/mL

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg/mL

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Median

Full Range

hours

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg*h/mL

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg*h/mL

Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg*h/mL

Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg

Primary

Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

mcg/mL

Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Median

Full Range

hours

Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Apparent Clearance (CL/F) of Vemurafenib on Day 15

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

liters/hour (L/h)

Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Primary

Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15

Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

hours

Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Secondary

Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)

Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.

Efficacy population: all enrolled participants who received at least one dose of vemurafenib, had measurable target lesions at baseline based on RECIST 1.1 criteria, had no major protocol violations of inclusion/exclusion criteria, and had no other violations affecting efficacy assessments.

Posted

Number

percentage of participants

Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)

ID	Title	Description
OG000	Vemurafenib - All Cohorts	Participants received vemurafenib film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Secondary

Overall Survival (OS)

OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death.

Data for this outcome measure was not collected as the outcome was removed as per changes in planned analysis (protocol amendment).

Posted

Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)

ID	Title	Description
OG000	Vemurafenib - All Cohorts	Participants received vemurafenib film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Units	Counts
Participants	OG000

Primary

Accumulation Ratio of Vemurafenib on Day 15

Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.

PK population. Here, number of participants analyzed signifies participants evaluable for this outcome.

Posted

Mean

Standard Deviation

ratio

Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15

ID	Title	Description
OG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film coated tablet twice daily orally in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
OG002	Cohort 3 - Vemurafenib 720 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG0033 affected16 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Palpitations	Cardiac disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Dermoid cyst	Congenital, familial and genetic disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Keratosis follicular	Congenital, familial and genetic disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Porokeratosis	Congenital, familial and genetic disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Deafness unilateral	Ear and labyrinth disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Cushingoid	Endocrine disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Binocular eye movement disorder	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Conjunctivitis	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Diplopia	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Dry eye	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Episcleritis	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Eye irritation	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Eye swelling	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Eyelid irritation	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Eyelid ptosis	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Ocular discomfort	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Periorbital oedema	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pupils unequal	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Retinal disorder	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Visual impairment	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0016 affected12 at risk EG0022 affected12 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0015 affected12 at risk EG0025 affected12 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Faecal incontinence	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Glossodynia	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Lip dry	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0007 affected12 at risk EG0015 affected12 at risk EG0026 affected12 at risk EG003
Oral disorder	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Oral mucosal blistering	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Salivary gland calculus	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Salivary gland mass	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected12 at risk EG0013 affected12 at risk EG0022 affected12 at risk EG003
Asthenia	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0023 affected12 at risk EG003
Axillary pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Chest discomfort	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Chest pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Chills	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Cyst	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Early satiety	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Face oedema	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Fatigue	General disorders	MedDRA 16.0	Non-systematic Assessment	EG00010 affected12 at risk EG0017 affected12 at risk EG0028 affected12 at risk EG003
Gait disturbance	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hyperplasia	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Induration	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Influenza like illness	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Irritability	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Malaise	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Medical device pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Mucosal inflammation	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Nodule	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Oedema	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Oedema peripheral	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG003
Pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Pyrexia	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0023 affected12 at risk EG003
Spinal pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Suprapubic pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Swelling	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Temperature intolerance	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Xerosis	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Abscess	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Cellulitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0023 affected12 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Folliculitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Fungal infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Gingivitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Hordeolum	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Oral herpes	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rhinitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Sinusitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Tinea pedis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0024 affected12 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Vulvitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Cartilage injury	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Incision site oedema	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Incision site pain	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Radiation necrosis	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Scar	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Skin wound	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Sunburn	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0005 affected12 at risk EG0011 affected12 at risk EG0026 affected12 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Wound secretion	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Amylase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Blast cell count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Blood albumin decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Blood creatinine increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0010 affected12 at risk EG0023 affected12 at risk EG003
Blood lactate dehydrogenase decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Blood phosphorus increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Blood urea increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Breath sounds abnormal	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Carbon dioxide decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Cardiac murmur	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Eosinophil count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Glomerular filtration rate decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Glomerular filtration rate increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Granulocyte count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Lipase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Liver function test abnormal	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Lymph node palpable	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Mean cell haemoglobin concentration increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Mean cell volume increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Mean platelet volume decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Metamyelocyte count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Monocyte count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Myelocyte count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Promyelocyte count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Protein total decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Protein total increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Protein urine present	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Red cell distribution width increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Specific gravity urine decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Specific gravity urine increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Urine ketone body present	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Urine leukocyte esterase positive	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Urine output increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Weight decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0005 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG003
Weight increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
White blood cells urine positive	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0014 affected12 at risk EG0024 affected12 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Zinc deficiency	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0008 affected12 at risk EG0015 affected12 at risk EG0029 affected12 at risk EG003
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Lower extremity mass	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Muscle atrophy	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0023 affected12 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0013 affected12 at risk EG0023 affected12 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0016 affected12 at risk EG0023 affected12 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Plantar fasciitis	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Upper extremity mass	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Acanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Acrochordon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Fibrous histiocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0013 affected12 at risk EG0024 affected12 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Warty dyskeratoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Amnesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Aphasia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Ataxia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Convulsion	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Coordination abnormal	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Dizziness	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0023 affected12 at risk EG003
Dysguesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0013 affected12 at risk EG0023 affected12 at risk EG003
Headache	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0014 affected12 at risk EG0021 affected12 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Hyperaesthesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Memory impairment	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Nystagmus	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Presyncope	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Sensory disturbance	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Somnolence	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Speech disorder	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Syncope	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
VII nerve paralysis	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Delirium	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Depression	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Illusion	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0023 affected12 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Mood altered	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Self-induced vomiting	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Urinary tract disorder	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Urine flow decreased	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Breast mass	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Female genital tract fistula	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Menometrorrhagia	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Nipple pain	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Prostatomegaly	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Testicular pain	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Vulvovaginal pruritus	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0012 affected12 at risk EG0023 affected12 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Nocturnal dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0013 affected12 at risk EG0022 affected12 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Tonsillar disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0011 affected12 at risk EG0025 affected12 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0007 affected12 at risk EG0013 affected12 at risk EG0022 affected12 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Butterfly rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Dermatitis exfoliative	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0014 affected12 at risk EG0023 affected12 at risk EG003
Erythema nodosum	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Heat rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected12 at risk EG0012 affected12 at risk EG0026 affected12 at risk EG003
Ingrown hair	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Keratosis pilaris	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected12 at risk EG0021 affected12 at risk EG003
Lentigo	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Leukoplakia	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Lichenoid keratosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Macule	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Milia	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Papule	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0012 affected12 at risk EG0020 affected12 at risk EG003
Parakeratosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Perivascular dermatitis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected12 at risk EG0013 affected12 at risk EG0025 affected12 at risk EG003
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0017 affected12 at risk EG0025 affected12 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Rash follicular	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0022 affected12 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Sebaceous gland disorder	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0022 affected12 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0013 affected12 at risk EG0023 affected12 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0014 affected12 at risk EG0021 affected12 at risk EG003
Skin plaque	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Transient acantholytic dermatosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Sinus operation	Surgical and medical procedures	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Extremity necrosis	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Flushing	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003
Hot flush	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hypertension	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hypotension	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Lymphoedema	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0021 affected12 at risk EG003

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description
BG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
BG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
BG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
BG003	Cohort 4 - Vemurafenib 960 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
BG004	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1 - Vemurafenib 240 mg	Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.	3	12	12	12
EG001	Cohort 2 - Vemurafenib 480 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.	3	12	12	12
EG002	Cohort 3 - Vemurafenib 720 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.	8	12	12	12
EG003	Cohort 4 - Vemurafenib 960 mg	Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.	7	16	16	16

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0012 affected12 at risk EG0022 affected12 at risk EG0032 affected16 at risk
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Squamous cell carcinoma of the oral cavity	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected12 at risk EG0020 affected12 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Pyrexia	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003
Hypotension	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Shock	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Device related infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected12 at risk EG0020 affected12 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected12 at risk EG0021 affected12 at risk EG003