This is a Phase Ib, open-label, multiple-center, multiple-dose study designed to evaluate the pharmacokinetics and safety of vismodegib in patients with advanced solid malignancies (including hepatocellular carcinoma and lymphoma) that are refractory to standard therapy or for whom no standard therapy exists.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
oral repeating dose of 150 mg once daily
Unnamed facility
Chicago, Illinois, United States
Unnamed facility
Baltimore, Maryland, United States
Unnamed facility
Detroit, Michigan, United States
Unnamed facility
Lebanon, New Hampshire, United States
Unnamed facility
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
Time frame: 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).
Time frame: Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8
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
Time frame: 24 hr total interval on Day 8
Renal Clearance of Vismodegib
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
Amount of Vismodegib Excreted Into Urine in 24 Hours (Ae0-24hr)
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New York, New York, United States
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
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.
Time frame: Up to 8 days
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.
Time frame: Up to 8 days
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.
Time frame: Up to 8 days
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.
Time frame: Up to 8 days