JNJ-42756493

The Cmax is the maximum observed plasma concentration.

The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

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

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vd/F) is influenced by the fraction absorbed.

Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

The Cmax is the maximum observed plasma concentration.

The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

The Ae is the amount of drug excreted in urine. It is calculated by multiplying the urinary volume with the urinary drug concentration.

Renal clearance calculated as Ae/AUC (last).

AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el\^2) summation\[(tn - tn\^-1) (Cn\^-1) (tn\^-1)\] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant.

Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, calculated as 0.693/Lamda(z).

The Ae%dose is the percentage of drug dose excreted into the urine calculated as (Ae divided by dose)∗100.

Amount of drug excreted into urine over a given time interval from t1 to t2, where t1 and t2 are the start and end times of the interval.

Percentage of the AUCinfinity obtained by extrapolation calculated by ratio between AUCinfinity minus AUClast versus AUCinfinity.

RP2D will be determined based on pharmacodynamics, biomarker response or clinical response, as well as the incidence rate and nature of the toxicities observed.

Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.

The Cmax is the maximum observed plasma concentration of JNJ-42756493.

Absolute bioavailability will be measured by Area under concentration time-curve (AUC \[0-24\]), AUC (0-last) and AUC (0-infinity).

Relative bioavailability will be measured by AUC (0-24), AUC (0-last) and AUC (0-infinity).

The F (abs) is the percentage of the orally administered dose that is systemically available. It is calculated as (AUC \[0-infinity\] for test)/(AUC \[0-infinity\] for reference \[ref\])\*(D for ref/D for test )\*100, where the reference treatment is an intravenous administration, AUC (0-infinity) is area under the concentration-time curve from time zero to extrapolated infinite time, and D is the dose of orally administered drug.

The F (rel) is the percentage of the orally administered dose that is systemically available. It is calculated as (AUC \[0-infinity\] for test)/(AUC \[0-infinity\] for reference \[ref\])\*(D for test/D for ref )\*100, where the reference treatment is an intravenous administration, AUC (0-infinity) is area under the concentration-time curve from time zero to extrapolated infinite time, and D is the dose of orally administered drug.