A Study of the Effect of Food on the Pharmacokinetics of... | NCT01264380

Label	Type	Intervention Names
1	Experimental	Drug: RO5185426
2	Experimental	Drug: RO5185426
C	Experimental	Drug: RO5185426

Name	Type	Description	Arm Group Labels	Other Names
RO5185426	Drug	Single oral dose, fasted	1
RO5185426

Measure	Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States	Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.	Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States	PK analyses was performed after the completion of Period A and Period B of this study for all participants.	Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States	PK analyses was performed after the completion of Period A and Period B of this study for all participants.	Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States	Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.	Pre-dose on Periods A and B
Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States

Measure	Description	Time Frame
Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)	BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		La Jolla	California	92037	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.

ID	Title	Description
FG000	Vemurafenib (RO5185426): Fasted Then Fed	Single oral dose of vemurafenib tablet at 960 milligrams (mg) on Day 1 was administered to participants in fasted condition (Period A [Day 1 to Day 10]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fed condition (Period B [Day 11 to Day 20]). A washout period of 10 days was maintained between Period A and B.

ID	Title	Description
BG000	All Participants	Included all participants who received single oral dose of vemurafenib tablet at 960 mg in fasted condition first and fed condition first in Period A and Period B and twice daily dose of vemurafenib tablet at 960 mg in Period C.

Units	Counts
Participants	BG00016

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 Infinity (AUC [0-inf]) in the Fasted and Fed States

Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population included participants who received both single doses of vemurafenib in Periods A and B without protocol violation and provided adequate PK assessments to calculate important PK parameters. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

micrograms*hour per milliliter (µg*h/mL)

Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Units	Counts
Participants	OG00016 OG00115

Title

Denominators

Categories

Title	Measurements
	OG000115± 110 OG001351± 189

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The point estimate and 90 percent (%) confidence interval (CI) of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.					Ratio of Geometric Mean	4.64			2-Sided	90	2.83	7.60				No	Superiority or Other

Primary

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States

PK analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

µg*h/mL

Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Units	Counts
Participants

Primary

Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States

PK analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population.

Posted

Mean

Standard Deviation

µg/mL

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Units	Counts
Participants	OG000

Primary

Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States

Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population.

Posted

Mean

Standard Deviation

µg/mL

Pre-dose on Periods A and B

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Units	Counts
Participants	OG000

Primary

Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States

PK analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population.

Posted

Median

Full Range

hour

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Units	Counts
Participants	OG000

Primary

Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States

T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

hour

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Units	Counts
Participants

Primary

Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States

Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

1/h

ID	Title	Description
OG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
OG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).

Secondary

Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)

BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Intent-to-treat (ITT) population included participants with measurable disease who received at least 1 dose of vemurafenib. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124)

ID	Title	Description
OG000	Vemurafenib (RO5185426)	Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).

Secondary

Overall Survival (OS)

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

Data for OS was not collected as there was a change in planned analysis, not to collect the data.

Posted

From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124)

ID	Title	Description
OG000	Vemurafenib (RO5185426)	Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haemorrhagic diathesis	Blood and lymphatic system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Sinus bradycardia	Cardiac disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Tachycardia	Cardiac disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0022 affected16 at risk
Blepharitis	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Cataract	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Diplopia	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dry eye	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Eye irritation	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Eye pain	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Lacrimation increased	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected16 at risk
Ocular hyperaemia	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Ocular rosacea	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Photophobia	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Vision blurred	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Vitreous floaters	Eye disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Abdominal distention	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Cheilitis	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Constipation	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0026 affected16 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Gingival pain	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Lip swelling	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0025 affected16 at risk
Oral disorder	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Toothache	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Chest discomfort	General disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Chills	General disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Fatigue	General disorders	MedDRA (16.0)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected16 at risk EG00210 affected16 at risk
Influenza like illness	General disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Oedema peripheral	General disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Pyrexia	General disorders	MedDRA (16.0)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Bronchitis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Chronic sinusitis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Conjunctivitis infective	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Nasopharyngitis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Onychomycosis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Oral candidiasis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Pneumonia pseudomonas aeruginosa	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Sinusitis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Incision site pain	Injury, poisoning and procedural complications	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Blood creatinine increased	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Breath sounds abnormal	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Neutrophil count increased	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0025 affected16 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG00210 affected16 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Sensation of heaviness	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dysplastic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0020 affected16 at risk
Pyogenic granuloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Aphasia	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dizziness	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Dysgeusia	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Headache	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0025 affected16 at risk
Paraesthesia	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Agitation	Psychiatric disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Anxiety	Psychiatric disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Claustrophobia	Psychiatric disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Depression	Psychiatric disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Insomnia	Psychiatric disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Mental status changes	Psychiatric disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Haematuria	Renal and urinary disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Proteinuria	Renal and urinary disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Gynaecomastia	Reproductive system and breast disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Acne Conglobata	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0025 affected16 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Erythema nodosum	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Granuloma skin	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG00212 affected16 at risk
Neurodermatitis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Panniculitis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0027 affected16 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0024 affected16 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0026 affected16 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Skin hypertrophy	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Skin mass	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Hypertension	Vascular disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0023 affected16 at risk
Hypotension	Vascular disorders	MedDRA (16.0)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected16 at risk EG0021 affected16 at risk
Vasculitis	Vascular disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Dyspnoea Paroxysmal Nocturna	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk

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	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vemurafenib (RO5185426): Fasted	Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).	0	16	3	16
EG001	Vemurafenib (RO5185426): Fed	Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).	0	16	5	16
EG002	Vemurafenib (RO5185426)	Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).	9	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	EG0000 affected16 at risk EG0010 affected16 at risk EG0025 affected16 at risk
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0022 affected16 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Coronary artery disease	Cardiac disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Cellulitis	Infections and infestations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Transaminases increased	Investigations	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA (16.0)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk