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Trial record 30 of 78 for:    vismodegib

A Study of Vismodegib in Patients With Advanced Solid Malignancies Including Hepatocellular Carcinoma With Varying Degrees of Renal or Hepatic Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01546519
Recruitment Status : Completed
First Posted : March 7, 2012
Results First Posted : May 23, 2016
Last Update Posted : May 23, 2016
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cancer
Intervention Drug: Vismodegib
Enrollment 31
Recruitment Details This was an open-label study with no randomization. Participants were categorized according to their baseline renal and hepatic function, and assigned to one of the five cohorts.
Pre-assignment Details After assessing the additional data since the study initiation and after discussions with regulators, the sponsor concluded that renal impairment does not impact the pharmacokinetics of vismodegib and, therefore, a dedicated renal impairment cohort was eliminated.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description 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.

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.

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.

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.

Period Title: Overall Study
Started 9 8 8 6
Safety-Evaluable Participants 9 8 8 6
Completed 0 0 0 0
Not Completed 9 8 8 6
Reason Not Completed
Adverse Event             0             0             1             1
Death             0             1             3             1
related to disease progression             2             2             2             1
Physician Decision             6             5             2             3
Withdrawal by Subject             1             0             0             0
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI) Total
Hide Arm/Group Description

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.

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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 9 8 8 6 31
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 8 participants 8 participants 6 participants 31 participants
63.3  (12.6) 60.6  (14.1) 65.8  (10.7) 64.0  (8.4) 63.4  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 8 participants 6 participants 31 participants
Female
1
  11.1%
3
  37.5%
2
  25.0%
1
  16.7%
7
  22.6%
Male
8
  88.9%
5
  62.5%
6
  75.0%
5
  83.3%
24
  77.4%
1.Primary Outcome
Title Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib
Hide Description 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
Time Frame Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population: A participant was considered evaluable for the PK analyses if he or she had a full profile of vismodegib samples
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 9 8 6 3
Mean (Standard Deviation)
Unit of Measure: micromolar
Cmax 23.6  (9.39) 30.7  (13.10) 30.5  (11.60) 20.5  (9.53)
Css 21.6  (9.17) 26.9  (12.4) 27.2  (10.5) 19.1  (9.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Mild Hepatic Impairment and Normal Renal Function (Mild HI)
Comments Cmax Mild HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.30
Confidence Interval (2-Sided) 90%
0.95 to 1.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Moderate Hepatic Impairment and Normal Renal Function (Mod HI)
Comments Cmax Moderate HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.30
Confidence Interval (2-Sided) 90%
0.92 to 1.83
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Comments Cmax Severe HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 90%
0.55 to 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Mild Hepatic Impairment and Normal Renal Function (Mild HI)
Comments Css Mild HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.24
Confidence Interval (2-Sided) 90%
0.90 to 1.71
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Moderate Hepatic Impairment and Normal Renal Function (Mod HI)
Comments Css Moderate HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.27
Confidence Interval (2-Sided) 90%
0.89 to 1.80
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Comments Css Severe HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 90%
0.55 to 1.41
Estimation Comments [Not Specified]
2.Primary Outcome
Title The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib
Hide Description 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).
Time Frame Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population: A participant was considered evaluable for the PK analyses if he or she had a full profile of vismodegib samples
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 9 8 6 3
Mean (Standard Deviation)
Unit of Measure: Micromolar*hour
512  (222) 639  (304) 667  (274) 437  (197)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Mild Hepatic Impairment and Normal Renal Function (Mild HI)
Comments AUC0-24hr Mild HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.24
Confidence Interval (2-Sided) 90%
0.89 to 1.73
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Moderate Hepatic Impairment and Normal Renal Function (Mod HI)
Comments AUC0-24hr Moderate HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.31
Confidence Interval (2-Sided) 90%
0.91 to 1.89
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Control Cohort With Normal Renal and Normal Hepatic Function, Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Comments AUC0-24hr Severe HI vs. Normal: Based on pooled variance estimates
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 90%
0.53 to 1.39
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Percentage of Dose of Vismodegib in 24-hour Total Urine
Hide Description The percentage of dose vismodegib excreted in urine over a 24-hr total interval was estimated
Time Frame 24 hr total interval on Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 8 7 3 3
Mean (Standard Deviation)
Unit of Measure: % Dose Excreted in 24 hr
0.792  (0.579) 0.283  (0.253) 0.104  (0.0485) 0.201  (0.135)
4.Secondary Outcome
Title Renal Clearance of Vismodegib
Hide Description Renal clearance (CLR) is defined as the apparent total clearance of the drug from plasma after oral administration.
Time Frame 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 8 7 3 3
Mean (Standard Deviation)
Unit of Measure: Liter/hour
6.76  (5.73) 1.97  (2.24) 0.618  (0.31) 2.06  (1.53)
5.Secondary Outcome
Title Amount of Vismodegib Excreted Into Urine in 24 Hours (Ae0-24hr)
Hide Description The amount of total vismodegib excreted in urine over a 24-hr total interval (Ae0-24hr) was estimated.
Time Frame 24 hr total interval on Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:

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.

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.

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.

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.

Overall Number of Participants Analyzed 8 7 3 3
Mean (Standard Deviation)
Unit of Measure: milligrams/24 hour
1.19  (0.869) 0.425  (0.380) 0.156  (0.0728) 0.301  (0.203)
6.Secondary Outcome
Title Time to Maximum Plasma Concentration (Tmax) of Vismodegib
Hide Description 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.
Time Frame Up to 8 days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:
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.

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.

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.

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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Minimum Plasma Concentration (Cmin) of Vismodegib
Hide Description 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.
Time Frame Up to 8 days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:
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.

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.

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.

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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Apparent Clearance (CL/F) of Vismodegib
Hide Description 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.
Time Frame Up to 8 days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:
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.

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.

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.

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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Apparent Non-renal Clearance (CLNR/F) of Vismodegib
Hide Description 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.
Time Frame Up to 8 days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description:
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.

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.

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.

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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Up to 60 days
Adverse Event Reporting Description AEs and SAEs were collected for all the participants who received at least one dose of study medication.
 
Arm/Group Title Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Hide Arm/Group Description

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.

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.

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.

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.

All-Cause Mortality
Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/9 (33.33%)   4/8 (50.00%)   6/8 (75.00%)   3/6 (50.00%) 
Cardiac disorders         
Atrial fibrillation  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  0/9 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/6 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/9 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/6 (0.00%) 
Ascites  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Haematemesis  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Nausea  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Oesophageal varices haemorrhage  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Small intestinal obstruction  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Vomiting  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
General disorders         
Chills  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Drug withdrawal syndrome  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Fatigue  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Pain  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Pyrexia  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders         
Hyperbilirubinaemia  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  2/6 (33.33%) 
Cholangitis  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Infections and infestations         
Pneumococcal sepsis  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Wound infection  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders         
Hyponatraemia  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Tumour Haemorrhage  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Nervous system disorders         
Haemorrhage Intracranial  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Mediastinal haemorrhage  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Pleural effusion  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Control Cohort With Normal Renal and Normal Hepatic Function Mild Hepatic Impairment and Normal Renal Function (Mild HI) Moderate Hepatic Impairment and Normal Renal Function (Mod HI) Severe Hepatic Impairment and Normal Renal Function (Sev HI)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/9 (88.89%)   7/8 (87.50%)   8/8 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders         
Anaemia  1  0/9 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%) 
Leukocytosis  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Eye disorders         
Dry eye  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders         
Abdominal distension  1  0/9 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/6 (0.00%) 
Abdominal pain  1  1/9 (11.11%)  0/8 (0.00%)  3/8 (37.50%)  1/6 (16.67%) 
Abdominal pain upper  1  1/9 (11.11%)  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%) 
Ascites  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  2/6 (33.33%) 
Constipation  1  2/9 (22.22%)  0/8 (0.00%)  3/8 (37.50%)  0/6 (0.00%) 
Diarrhoea  1  0/9 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%) 
Dry mouth  1  1/9 (11.11%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Epigastric discomfort  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Gastrooesophageal reflux disease  1  0/9 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%) 
Gingival bleeding  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Melaena  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Nausea  1  3/9 (33.33%)  3/8 (37.50%)  3/8 (37.50%)  2/6 (33.33%) 
Vomiting  1  1/9 (11.11%)  3/8 (37.50%)  1/8 (12.50%)  1/6 (16.67%) 
General disorders         
Asthenia  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Early satiety  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Fatigue  1  5/9 (55.56%)  5/8 (62.50%)  7/8 (87.50%)  4/6 (66.67%) 
Gait disturbance  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Malaise  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Oedema  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Oedema peripheral  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Pain  1  0/9 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/6 (0.00%) 
Pyrexia  1  1/9 (11.11%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Hepatobiliary disorders         
Hyperbilirubinaemia  1  2/9 (22.22%)  0/8 (0.00%)  2/8 (25.00%)  1/6 (16.67%) 
Infections and infestations         
Cellulitis  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Clostridium difficile infection  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications         
Patella fracture  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Aspartate aminotransferase increased  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Blood bilirubin increased  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
International normalised ratio increased  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Waist circumference increased  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Weight decreased  1  1/9 (11.11%)  3/8 (37.50%)  1/8 (12.50%)  0/6 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  2/9 (22.22%)  2/8 (25.00%)  2/8 (25.00%)  1/6 (16.67%) 
Dehydration  1  1/9 (11.11%)  2/8 (25.00%)  0/8 (0.00%)  0/6 (0.00%) 
Gout  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Hypoalbuminaemia  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Hypokalaemia  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Hypomagnesaemia  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Hyponatraemia  1  0/9 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%) 
Hypophosphataemia  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Flank pain  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Muscle spasms  1  2/9 (22.22%)  2/8 (25.00%)  2/8 (25.00%)  0/6 (0.00%) 
Muscular weakness  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Musculoskeletal pain  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Neck pain  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cancer pain  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Nervous system disorders         
Amnesia  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Cerebrovascular accident  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Dizziness  1  0/9 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/6 (0.00%) 
Dysgeusia  1  1/9 (11.11%)  2/8 (25.00%)  2/8 (25.00%)  2/6 (33.33%) 
Encephalopathy  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Hepatic encephalopathy  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  2/6 (33.33%) 
Hypoaesthesia  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Hypogeusia  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Hyposmia  1  2/9 (22.22%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Neuropathy peripheral  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Vertebral artery stenosis  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Psychiatric disorders         
Agitation  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Anxiety  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  1/6 (16.67%) 
Confusional state  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  1/6 (16.67%) 
Depression  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Hallucination  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Insomnia  1  0/9 (0.00%)  3/8 (37.50%)  0/8 (0.00%)  0/6 (0.00%) 
Libido decreased  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders         
Renal impairment  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Reproductive system and breast disorders         
Genital lesion  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Cough  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Dyspnoea exertional  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Pleuritic pain  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Drug eruption  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Hair colour changes  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Hair texture abnormal  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Night sweats  1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%) 
Pruritus  1  0/9 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  1/6 (16.67%) 
Rash  1  1/9 (11.11%)  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%) 
Skin mass  1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%) 
Vascular disorders         
Arteriosclerosis  1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/6 (16.67%) 
Hot flush  1  0/9 (0.00%)  2/8 (25.00%)  0/8 (0.00%)  0/6 (0.00%) 
Venous thrombosis  1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights
Results Point of Contact
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 61 6878333
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01546519     History of Changes
Other Study ID Numbers: GP27839
First Submitted: March 2, 2012
First Posted: March 7, 2012
Results First Submitted: October 13, 2015
Results First Posted: May 23, 2016
Last Update Posted: May 23, 2016