Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Area under the concentration-time curve over the dosing interval on multiple dosing (AUC[0-t]) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. AUC(0-t) is defined as the area under the concentration-time profile from time zero to the end of the dosing interval at steady state. AUC represents the total drug exposure over a defined period of time. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Primary |
Time at which the highest drug concentration occurs at steady-state (tss,max) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. tss,max is the time at which the maximum concentration of lenvatinib is observed in the plasma at steady state, which occurs when the rates of drug administration and drug elimination are equal. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Primary |
Average steady-state concentration (Css,av) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,av is the average concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when the rates of drug administration and drug elimination are equal. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Primary |
Minimum observed concentration at steady-state (Css,min) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,min is the lowest concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when the rates of drug administration and drug elimination are equal. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15 |
|
Primary |
Maximum observed concentration at steady-state (Css,max) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,max is the highest concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when rates of drug administration and drug elimination are equal. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Primary |
Area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t]) |
Blood samples will be collected to determine the plasma lenvatinib concentration at various time points. AUC(0-t) is defined as the AUC from time "0" to the time of the last measurable concentration. AUC represents the total drug exposure over a defined period of time. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Primary |
Time at which the highest drug concentration occurs (tmax) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Tmax is the time at which the maximum concentration of lenvatinib is observed in plasma after a single dose of lenvatinib. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Primary |
Maximum observed concentration (Cmax) |
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Cmax is the highest concentration of lenvatinib observed in plasma after a single dose of lenvatinib. |
Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15) |
|
Secondary |
Mean blood urea nitrogen (BUN) values |
Blood samples will be collected to determine the amount of nitrogen in the blood. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean creatinine values |
Blood chemistry tests will be performed to determine serum creatinine levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean albumin values |
Blood chemistry tests will be performed to determine serum albumin values. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean cholesterol values |
Blood chemistry tests will be performed to determine cholesterol levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean lactate dehydrogenase values |
Blood chemistry tests will be performed to determine serum lactate dehydrogenase levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean total protein values |
Blood chemistry tests will be performed to determine total protein levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean C-reactive protein (CRP) values |
Blood chemistry tests will be performed to determine CRP levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean gamma-glutamyl transpeptidase (?-GTP) values |
Blood chemistry tests will be performed to determine ?-GTP levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean total bilirubin values |
Blood chemistry tests will be performed to determine total bilirubin levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean alanine transaminase (ALT) values |
ALT is a transaminase enzyme and is commonly measured clinically as a biomarker for liver health. ALT will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean aspartate transaminase (AST) values |
AST is a pyridoxal phosphate-dependent transaminase enzyme and is commonly measured clinically as a biomarker for liver health. AST will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean alkaline phosphatase (ALP) values |
ALP is a hydrolase enzyme responsible for the dephosphorylation of molecules, including nucleotides, proteins, and alkaloids, and is commonly measured clinically as a biomarker for liver health. ALP will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean body temperature |
Body temperature in degrees Celsius will be analyzed from the armpit of the participants. Body temperature will be summarized as the mean and standard deviation for all participants |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean body weight |
Body weight of the participants will be measured in kilograms (kg). It will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean heart rate |
Heart rate of the participants will be measured in beats per minute (bpm). It will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean QT values |
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QT values will be measured in milliseconds (msec) and will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean QT corrected (QTc) values |
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTc values will be measured in milliseconds (msec) and it will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean QTc corrected using Fridericia's method (QTcF) values |
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTcF values will be measured in msec and will be summarized as the mean and standard deviation for all participants. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Number of participants with abnormal, clinically significant physical examination findings |
Physical examinations will be performed to determine abnormal findings that meet the definition of an AE. Clinical significance will be determined by the Investigator. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean calcium values |
Blood chemistry tests will be performed to determine calcium levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean chloride values |
Blood chemistry tests will be performed to determine chloride levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean potassium values |
Blood chemistry tests will be performed to determine potassium levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean sodium values |
Blood chemistry tests will be performed to determine sodium levels. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean lymphocyte count |
Hematology tests will be performed to determine the lymphocyte count in blood. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean neutrophil count |
Hematology tests will be performed to determine the neutrophil count in blood. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean white blood cell (WBC) count |
Hematology tests will be performed to determine the WBC count in blood. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean platelet count |
Hematology tests will be performed to determine the platelet count in blood. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean hemoglobin values |
Hematology tests will be performed to determine the hemoglobin levels in blood. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean red blood cell (RBC) count |
Hematology tests will be performed to determine the RBC count in blood. Participants should be in a seated or supine position during blood collection. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Number of participants with any serious adverse event and any non-serious adverse event |
An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; or is a congenital abnormality/birth defect. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean protein in urine values |
Urine samples will be collected to determine the amount of protein in the urine. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean glucose in urine values |
Urine samples will be collected to determine the amount of glucose in the urine. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean occult blood in urine values |
Urine samples will be collected to determine the amount of microscopic blood in the urine. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean systolic blood pressure and diastolic blood pressure values |
Blood pressure will be measured after the participant has been sitting. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
|
Secondary |
Mean pulse |
Pulse will be measured after the participant has been sitting. |
until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28) |
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