A Study of Vismodegib in Patients With Advanced Solid Mal... | NCT01546519

NCT01546519

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	Control cohort with normal renal and normal hepatic function	Drug: Vismodegib
2	Experimental	Severe renal impairment and normal hepatic function	Drug: Vismodegib
3	Experimental	Mild hepatic impairment and normal renal function	Drug: Vismodegib
4	Experimental	Moderate hepatic impairment and normal renal function	Drug: Vismodegib
5	Experimental	Severe hepatic impairment and normal renal function	Drug: Vismodegib

Name	Type	Description	Arm Group Labels	Other Names
Vismodegib	Drug	oral repeating dose of 150 mg once daily	1 2 3 4 5

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib	Maximum observed plasma Concentration (Cmax) & Concentration at steady-state (Css) following multiple doses of vismodegib (150 mg QD) were analyzed. At steady state the amount of drug administered (in a given time period) is equal to the amount of drug eliminated. Blood samples for assessing Cmax and Css for analysis were collected following multiple oral doses of vismodegib at pre-dose and at 0.5, 1, 2, 4, 8 and 24 hours post-dose on Day 8. From the plasma concentration-time curve, the PK parameter Cmax and Css were determined by standard non-compartmental analysis using WinNonlin	Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8
The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib	The steady state pharmacokinetic profile following oral administration of multiple doses of vismodegib included determining the area under the curve over the dosing interval (AUC[0-24 hours]). The AUC[0-24 hrs]) was determined by standard non-compartmental analysis using WinNonlin. Blood samples were collected at pre-dose and at 0.5, 1, 2, 4, 8 and 24 hours post-dose on Day 8 to estimate AUC(0-24 hrs).	Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8

Secondary Outcomes

Measure	Description	Time Frame
The Percentage of Dose of Vismodegib in 24-hour Total Urine	The percentage of dose vismodegib excreted in urine over a 24-hr total interval was estimated	24 hr total interval on Day 8
Renal Clearance of Vismodegib

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed advanced solid malignancy (including hepatocellular carcinoma and lymphoma) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/=60%)
Acceptable bone marrow functions
Normal or varying degrees of renal or hepatic impairment according to NCI Organ Dysfunction Working Group criteria.
Organ function should be stable for at least 2 weeks before Day 1. In addition, there should be no evidence of acute exacerbation of hepatic/renal disease.
Patients with gliomas or known brain metastases who require corticosteroids or anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to enrollment. Patients with known brain metastases must be at least 4 weeks out from any radiation before starting the protocol (Day 1).
Documented negative serum pregnancy test for women of childbearing potential
For women of childbearing potential, agreement to the use of two acceptable methods of contraception during the study and for 7 months after discontinuation of vismodegib
For men with female partners of childbearing potential, agreement to use a latex, non-latex, or any other male condom and to advise their female partners to use an additional acceptable method of birth control during the study and for 2 months after discontinuation of study drug
Agreement not to donate blood/blood products during the study and for 7 months after discontinuing study drug
For men with normal renal and hepatic function, agreement to provide semen during the vismodegib treatment period for study assessment (optional), but otherwise NOT to donate semen during the vismodegib treatment period and for 2 months after discontinuation of study drug

Exclusion Criteria:

Pregnancy or lactation
Chemotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Investigational agents within 28 days prior to study entry (Day 1)
Use of Pgp inhibitors within 7 days of Day 1
Use of gastric pH altering drugs except antacids within 7 days of Day 1
Major surgery within 14 days prior to treatment (Day 1). Patients with recent major surgery must have recovered from that surgery. Patients who are expected to have any major surgery during the study treatment period should not be enrolled.
Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of vismodegib or that might affect interpretation of the results from this study or renders the patient at high risk from treatment complications.
Severely impaired renal function (Cohort 2 only) should not have active hemolysis, and should not be on hemodialysis or peritoneal dialysis during the screening and study treatment period (Days 1-9).

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Genentech, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Chicago	Illinois	60637	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Renal clearance (CLR) is defined as the apparent total clearance of the drug from plasma after oral administration.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
BG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
BG002	Moderate Hepatic Impairment and Normal Renal Function (Mod HI)	Participants with moderate hepatic impairment and normal renal function were included. Moderate hepatic impairment was defined as 1.5 × ULN< TB<3× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
BG003	Severe Hepatic Impairment and Normal Renal Function (Sev HI)	Participants with severe hepatic impairment and normal renal function were included. Severe hepatic impairment is defined as 3×ULN<TB<10×ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0009 BG0018 BG0028 BG0036 BG00431

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Cmax

Title	Measurements
	OG00023.6± 9.39 OG00130.7± 13.10 OG00230.5± 11.60 OG003

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	Cmax Mild HI vs. Normal: Based on pooled variance estimates					Geometric mean ratio	1.30			2-Sided	90	0.95	1.78				No	Superiority or Other
OG000 OG002	Cmax Moderate HI vs. Normal: Based on pooled variance estimates

Primary

The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib

The steady state pharmacokinetic profile following oral administration of multiple doses of vismodegib included determining the area under the curve over the dosing interval (AUC[0-24 hours]). The AUC[0-24 hrs]) was determined by standard non-compartmental analysis using WinNonlin. Blood samples were collected at pre-dose and at 0.5, 1, 2, 4, 8 and 24 hours post-dose on Day 8 to estimate AUC(0-24 hrs).

Pharmacokinetic (PK) Population: A participant was considered evaluable for the PK analyses if he or she had a full profile of vismodegib samples

Posted

Mean

Standard Deviation

Micromolar*hour

Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)

Secondary

The Percentage of Dose of Vismodegib in 24-hour Total Urine

The percentage of dose vismodegib excreted in urine over a 24-hr total interval was estimated

Pharmacokinetic (PK) Population: A participant was considered evaluable for the PK analyses if he or she had a full profile of vismodegib samples. Participants available at particular time point for assessment were included in the analysis.

Posted

Mean

Standard Deviation

% Dose Excreted in 24 hr

24 hr total interval on Day 8

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Secondary

Renal Clearance of Vismodegib

Renal clearance (CLR) is defined as the apparent total clearance of the drug from plasma after oral administration.

Posted

Mean

Standard Deviation

Liter/hour

0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Secondary

Amount of Vismodegib Excreted Into Urine in 24 Hours (Ae0-24hr)

The amount of total vismodegib excreted in urine over a 24-hr total interval (Ae0-24hr) was estimated.

Posted

Mean

Standard Deviation

milligrams/24 hour

24 hr total interval on Day 8

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Secondary

Time to Maximum Plasma Concentration (Tmax) of Vismodegib

Tmax is the time to reach maximum plasma concentration of vismodegib. This was a pre-specified PK parameter. However, due to minimal fluctuation of Vismodegib concentrations at steady state, this parameter could not be determined.

PK population was the anticipated population for analysis. However, this outcome measure was not analyzed due to the minimal fluctuation of vismodegib concentrations at steady state.

Posted

Up to 8 days

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Secondary

Minimum Plasma Concentration (Cmin) of Vismodegib

Cmin is defined as the minimum observed plasma concentration of Vismodegib. This was a pre-specified PK parameter. However, due to minimal fluctuation of Vismodegib concentrations at steady state, this parameter could not be determined.

PK population was the anticipated population for analysis. However, this outcome measure was not analyzed due to the minimal fluctuation of vismodegib concentrations at steady state.

Posted

Up to 8 days

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Secondary

Apparent Clearance (CL/F) of Vismodegib

CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr). This was a pre-specified PK parameter. However, due to minimal fluctuation of vismodegib concentrations at steady state, this parameter could not be determined.

PK population was the anticipated population for analysis. However, this outcome measure was not analyzed due to the minimal fluctuation of vismodegib concentrations at steady state.

Posted

Up to 8 days

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Secondary

Apparent Non-renal Clearance (CLNR/F) of Vismodegib

Apparent Non-Renal Clearance (CLNR) describes the removal of vismodegib by organs other than the kidneys. This was a pre-specified PK parameter. However, due to minimal fluctuation of vismodegib concentrations at steady state, this parameter could not be determined.

PK population was the anticipated population for analysis. However, this outcome measure was not analyzed due to the minimal fluctuation of vismodegib concentrations at steady state.

Posted

Up to 8 days

ID	Title	Description
OG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
OG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Control Cohort With Normal Renal and Normal Hepatic Function	Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.	3	9	8	9
EG001	Mild Hepatic Impairment and Normal Renal Function (Mild HI)	Participants with mild hepatic impairment and normal renal function were included. Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.	4	8	7	8
EG002	Moderate Hepatic Impairment and Normal Renal Function (Mod HI)	Participants with moderate hepatic impairment and normal renal function were included. Moderate hepatic impairment was defined as 1.5 × ULN< TB<3× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.	6	8	8	8
EG003	Severe Hepatic Impairment and Normal Renal Function (Sev HI)	Participants with severe hepatic impairment and normal renal function were included. Severe hepatic impairment is defined as 3×ULN<TB<10×ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.	3	6	6	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0022 affected8 at risk EG0030 affected6 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0022 affected8 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Pneumococcal sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Wound infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Mediastinal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Chills	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Drug withdrawal syndrome	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Tumour Haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Haemorrhage Intracranial	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG0030 affected6 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Dry eye	Eye disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0022 affected8 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0023 affected8 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected9 at risk EG0010 affected8 at risk EG0023 affected8 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Epigastric discomfort	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected9 at risk EG0013 affected8 at risk EG0023 affected8 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0013 affected8 at risk EG0021 affected8 at risk EG003
Asthenia	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Early satiety	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected9 at risk EG0015 affected8 at risk EG0027 affected8 at risk EG003
Gait disturbance	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Malaise	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Oedema	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0022 affected8 at risk EG003
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected9 at risk EG0010 affected8 at risk EG0022 affected8 at risk EG003
Cellulitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Patella fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
International normalised ratio increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Waist circumference increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Weight decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0013 affected8 at risk EG0021 affected8 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected9 at risk EG0012 affected8 at risk EG0022 affected8 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0012 affected8 at risk EG0020 affected8 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected9 at risk EG0012 affected8 at risk EG0022 affected8 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Amnesia	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Dizziness	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0022 affected8 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0012 affected8 at risk EG0022 affected8 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Hepatic encephalopathy	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hypogeusia	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hyposmia	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Vertebral artery stenosis	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Agitation	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Depression	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Hallucination	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0013 affected8 at risk EG0020 affected8 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Genital lesion	Reproductive system and breast disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected9 at risk EG0011 affected8 at risk EG0021 affected8 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hot flush	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0012 affected8 at risk EG0020 affected8 at risk EG003
Venous thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected9 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003

ID	Term
D009369	Neoplasms

ID	Term
C538724	HhAntag691