Bioequivalence of TF3 and TF2 and Effect of Food on the PK of Tepotinib

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: Pharmacokinetic.(PK) Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Cmax was obtained directly from the concentration versus time curve.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator.

Time frame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator.

Time frame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

Vital sign assessment included blood pressure, pulse rate and body temperature. Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator.

Time frame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs.

Time frame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Vz/f was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) is influenced by the fraction absorbed and was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f after oral dose is influenced by the fraction absorbed.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Lambda z is the terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.