Hepatic Impairment
Conditions
Keywords
Hepatic Impairment, Tepotinib, Pharmacokinetics
Brief summary
The study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of tepotinib.
Interventions
DRUGTepotinib
Participants received a single oral dose of tepotinib in Part 1.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women (of nonchildbearing potential), with a body mass index of 18 to 36 kilograms per meter square (inclusive) and a body weight greater than or equal to 50 kilograms at screening, with the absence of acute hepatitis or Human Immunodeficiency Virus 1 and 2, who gave informed consent and are willing and able to comply with study procedures were eligible for enrollment * Participants with impaired hepatic function (Child-Pugh class A or Child-Pugh class B) and participants with normal hepatic function were eligible to enroll in the study * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Healthy participants were excluded if they have hepatitis B or C or had a previous infection with hepatitis C treated with Sofosbuvir or other antiviral compounds, or any other clinically relevant disease, as considered by the Investigator * Participants with impaired hepatic function were excluded if they have primary biliary liver cirrhosis, nonstabilized chronic heart failure, hepatocarcinoma, hepatic encephalopathy (Grade III or IV), sepsis or gastrointestinal bleeding, or any other clinically relevant disease, as considered by the Investigator * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | The area under the plasma concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down). |
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time profile. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Apparent volume of distribution during the terminal phase following extravascular administration for tepotinib was calculated. Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose. |
| Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- \[AUC0-t/AUC0-inf\])\*100. %AUCextra was reported in terms of percentage of AUC0-inf. |
| Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- \[AUC0-t/AUC0-inf\])\*100. %AUCextra was reported in terms of percentage of AUC0-inf. |
| Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- \[AUC0-t/AUC0-inf\])\*100. %AUCextra was reported in terms of percentage of AUC0-inf. |
| Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Area under the concentration-time curve for unbound drug from time zero to infinity, calculated as AUC0-inf\_pred multiplied by fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point. |
| Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Maximum unbound plasma drug concentration, was calculated as Cmax\*fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point. |
| Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Unbound apparent oral clearance, was calculated as CL/f,u = Dose divided by AUC0-inf\_pred/fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point. |
| Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | AUC0-t at which the concentration was at or above lower limit of quantification (LLOQ) was calculated according to the mixed log linear trapezoidal rule. Calculated using the mixed log-linear trapezoidal rule (linear up, log down). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Cmax was taken directly from the observed concentration-time profile. |
| Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | The area under the concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC0-inf = AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. Ratio of AUC0-inf of Metabolite (MSC2571109 or MSC2571107) to AUC0-inf of tepotinib was reported. |
| Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Cmax was taken directly from the observed concentration-time profile. Ratio of Cmax of Metabolite (MSC2571109 or MSC2571107) to Cmax of tepotinib was reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22 | An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs were reported. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22 | Laboratory assessments included hematology, biochemistry, coagulation and urinalysis. Number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22 | Vital signs included body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Number of participants with clinically significant changes from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator. |
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | The area under the concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC0-inf = AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Apparent Terminal Half Life (t1/2) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Apparent Total Body Clearance (CL/f) of Tepotinib | Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1 | Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for tepotinib. |
Countries
United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 parts: Part 1 and Part 2. Part 2 of the study was optional and sponsor decided not to perform part 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Participants (Control) Participants with normal hepatic function matched to moderate hepatic impairment received single oral dose of 500 milligrams (mg) of tepotinib film-coated tablet on Day 1 after a standard breakfast. | 6 |
| Mild Hepatic Impairment (Child-Pugh Class A) Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. | 6 |
| Moderate Hepatic Impairment (Child-Pugh Class B) Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Healthy Participants (Control) | Mild Hepatic Impairment (Child-Pugh Class A) | Moderate Hepatic Impairment (Child-Pugh Class B) | Total |
|---|---|---|---|---|
| Age, Continuous | 59 Years STANDARD_DEVIATION 8 | 61 Years STANDARD_DEVIATION 3.9 | 60 Years STANDARD_DEVIATION 10 | 60 Years STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib
The area under the plasma concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: Pharmacokinetic (PK) Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib | 27500 Nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 13.4 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib | 26100 Nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 63.9 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib | 24200 Nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26.9 |
90% CI: [64.75, 139.35]
90% CI: [59.93, 128.98]
Primary
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib | 27000 ng*h/mL | Geometric Coefficient of Variation 13.8 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib | 25600 ng*h/mL | Geometric Coefficient of Variation 65.6 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib | 23500 ng*h/mL | Geometric Coefficient of Variation 27.4 |
90% CI: [64.09, 140.26]
90% CI: [58.94, 129]
Primary
Maximum Observed Plasma Concentration (Cmax) of Tepotinib
Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time profile.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib | 406 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12.2 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib | 416 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31.5 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib | 288 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.5 |
90% CI: [80.9, 129.73]
90% CI: [56.08, 89.93]
Secondary
Apparent Terminal Half Life (t1/2) of Tepotinib
Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Participants (Control) | Apparent Terminal Half Life (t1/2) of Tepotinib | 36.8 Hours |
| Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Terminal Half Life (t1/2) of Tepotinib | 43.7 Hours |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Terminal Half Life (t1/2) of Tepotinib | 46.1 Hours |
Secondary
Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Participants (Control) | Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 46.3 Hours |
| Healthy Participants (Control) | Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 46.8 Hours |
| Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 57.5 Hours |
| Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 40.7 Hours |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 78.8 Hours |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 75.4 Hours |
Secondary
Apparent Total Body Clearance (CL/f) of Tepotinib
Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for tepotinib.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Apparent Total Body Clearance (CL/f) of Tepotinib | 16.4 Liter per hour | Geometric Coefficient of Variation 13.4 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Total Body Clearance (CL/f) of Tepotinib | 17.2 Liter per hour | Geometric Coefficient of Variation 63.9 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Total Body Clearance (CL/f) of Tepotinib | 18.6 Liter per hour | Geometric Coefficient of Variation 26.9 |
Secondary
Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib
Unbound apparent oral clearance, was calculated as CL/f,u = Dose divided by AUC0-inf\_pred/fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib | 845 Liter per hour | Geometric Coefficient of Variation 26.4 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib | 770 Liter per hour | Geometric Coefficient of Variation 40.5 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib | 689 Liter per hour | Geometric Coefficient of Variation 33.3 |
Secondary
Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib
Apparent volume of distribution during the terminal phase following extravascular administration for tepotinib was calculated. Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib | 892 Liter | Geometric Coefficient of Variation 11.4 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib | 1050 Liter | Geometric Coefficient of Variation 45.3 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib | 1400 Liter | Geometric Coefficient of Variation 20.4 |
Secondary
Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib
Area under the concentration-time curve for unbound drug from time zero to infinity, calculated as AUC0-inf\_pred multiplied by fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib | 532 ng*h/mL | Geometric Coefficient of Variation 26.4 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib | 585 ng*h/mL | Geometric Coefficient of Variation 40.5 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib | 653 ng*h/mL | Geometric Coefficient of Variation 33.3 |
Secondary
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
The area under the concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC0-inf = AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 13400 ng*h/mL | Geometric Coefficient of Variation 29.3 |
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 1130 ng*h/mL | Geometric Coefficient of Variation 33.7 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 11100 ng*h/mL | Geometric Coefficient of Variation 74.3 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 1140 ng*h/mL | Geometric Coefficient of Variation 87.2 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 18500 ng*h/mL | Geometric Coefficient of Variation 80.9 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 1080 ng*h/mL | Geometric Coefficient of Variation 69.2 |
90% CI: [45.56, 148.84]
90% CI: [76.08, 248.54]
90% CI: [55.16, 184.23]
90% CI: [52.63, 175.78]
Secondary
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
AUC0-t at which the concentration was at or above lower limit of quantification (LLOQ) was calculated according to the mixed log linear trapezoidal rule. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 13300 ng*h/mL | Geometric Coefficient of Variation 29.5 |
| Healthy Participants (Control) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 1120 ng*h/mL | Geometric Coefficient of Variation 34.1 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 11000 ng*h/mL | Geometric Coefficient of Variation 74.8 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 1120 ng*h/mL | Geometric Coefficient of Variation 88.8 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 18100 ng*h/mL | Geometric Coefficient of Variation 80.7 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 1050 ng*h/mL | Geometric Coefficient of Variation 70.4 |
90% CI: [45.67, 149.47]
90% CI: [75.5, 247.12]
90% CI: [54.53, 185.1]
90% CI: [51.28, 174.07]
Secondary
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib
AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- \[AUC0-t/AUC0-inf\])\*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK analysis set was used. Summary statistics for this parameter was not reported because it is a diagnostic parameter, rather than a PK parameter in the proper sense. It was only used to assess the individual data, not the group level. Therefore, individual data was reported for this outcome measure. Here, Number Analyzed= specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 1 | 1.34 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 2 | 1.06 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 3 | 2.14 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 4 | 1.22 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 5 | 2.45 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 6 | 2.08 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 6 | 1.41 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 1 | 5.01 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 4 | 1.16 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 5 | 1.55 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 2 | 0.895 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 3 | 1.33 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 2 | 3.03 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 3 | 1.49 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 6 | 3.87 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 4 | 1.80 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 1 | 3.35 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib | Participant 5 | 1.60 Percentage of AUC0-inf |
Secondary
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107)
AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- \[AUC0-t/AUC0-inf\])\*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK analysis set was used. Summary statistics for this parameter was not reported because it is a diagnostic parameter, rather than a PK parameter in the proper sense. It was only used to assess the individual data, not the group level. Therefore, individual data was reported for this outcome measure. Here, Number Analyzed= specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 1 | 0.592 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 2 | 0.925 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 3 | 0.671 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 4 | 0.639 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 5 | 1.77 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 6 | 0.904 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 6 | 1.15 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 1 | 3.69 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 4 | 0.513 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 5 | 0.731 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 2 | 0.848 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 3 | 0.516 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 2 | 5.68 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 3 | 0.683 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 6 | 1.97 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 4 | 3.08 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 1 | 2.10 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) | Participant 5 | 2.45 Percentage of AUC0-inf |
Secondary
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109)
AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- \[AUC0-t/AUC0-inf\])\*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK analysis set was used. Summary statistics for this parameter was not reported because it is a diagnostic parameter, rather than a PK parameter in the proper sense. It was only used to assess the individual data, not the group level. Therefore, individual data was reported for this outcome measure. Here, Number Analyzed= specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 1 | 0.799 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 2 | 1.28 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 3 | 0.737 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 4 | 0.677 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 5 | 1.55 Percentage of AUC0-inf |
| Healthy Participants (Control) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 6 | 1.07 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 6 | 0.621 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 1 | 1.44 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 4 | 0.470 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 5 | 0.482 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 2 | 0.574 Percentage of AUC0-inf |
| Mild Hepatic Impairment (Child-Pugh Class A) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 3 | 0.605 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 2 | 1.41 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 3 | 1.06 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 6 | 1.96 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 4 | 3.06 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 1 | 2.05 Percentage of AUC0-inf |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) | Participant 5 | 0.522 Percentage of AUC0-inf |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Cmax was taken directly from the observed concentration-time profile.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Participants (Control) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 143 ng/mL | Geometric Coefficient of Variation 33.9 |
| Healthy Participants (Control) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 13.9 ng/mL | Geometric Coefficient of Variation 39.2 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 132 ng/mL | Geometric Coefficient of Variation 47.3 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 14.8 ng/mL | Geometric Coefficient of Variation 55.2 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 165 ng/mL | Geometric Coefficient of Variation 37.9 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 10.1 ng/mL | Geometric Coefficient of Variation 32.1 |
90% CI: [62.52, 136.26]
90% CI: [77.76, 169.48]
90% CI: [70.25, 161.49]
90% CI: [47.87, 110.04]
Secondary
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib
Maximum unbound plasma drug concentration, was calculated as Cmax\*fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Participants (Control) | Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib | 7.87 ng/mL | Geometric Coefficient of Variation 25.6 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib | 9.32 ng/mL | Geometric Coefficient of Variation 22.5 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib | 7.80 ng/mL | Geometric Coefficient of Variation 22.3 |
Secondary
Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio
The area under the concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC0-inf = AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. Ratio of AUC0-inf of Metabolite (MSC2571109 or MSC2571107) to AUC0-inf of tepotinib was reported.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Participants (Control) | Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | MSC2571109 | 0.489 Ratio | Geometric Coefficient of Variation 31.8 |
| Healthy Participants (Control) | Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | MSC2571107 | 0.0410 Ratio | Geometric Coefficient of Variation 34.7 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | MSC2571109 | 0.424 Ratio | Geometric Coefficient of Variation 24.7 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | MSC2571107 | 0.0435 Ratio | Geometric Coefficient of Variation 32.3 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | MSC2571109 | 0.764 Ratio | Geometric Coefficient of Variation 49.5 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio | MSC2571107 | 0.0449 Ratio | Geometric Coefficient of Variation 40 |
Secondary
Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio
Cmax was taken directly from the observed concentration-time profile. Ratio of Cmax of Metabolite (MSC2571109 or MSC2571107) to Cmax of tepotinib was reported.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Participants (Control) | Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | MSC2571109 | 0.353 Ratio | Geometric Coefficient of Variation 27.5 |
| Healthy Participants (Control) | Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | MSC2571107 | 0.0343 Ratio | Geometric Coefficient of Variation 29.2 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | MSC2571109 | 0.318 Ratio | Geometric Coefficient of Variation 30 |
| Mild Hepatic Impairment (Child-Pugh Class A) | Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | MSC2571107 | 0.0357 Ratio | Geometric Coefficient of Variation 32.9 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | MSC2571107 | 0.0351 Ratio | Geometric Coefficient of Variation 27.1 |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio | MSC2571109 | 0.571 Ratio | Geometric Coefficient of Variation 37.3 |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory assessments included hematology, biochemistry, coagulation and urinalysis. Number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator.
Time frame: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Population: Safety Analysis Set included all participants who received tepotinib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Participants (Control) | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
| Mild Hepatic Impairment (Child-Pugh Class A) | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings
Vital signs included body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Number of participants with clinically significant changes from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator.
Time frame: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Population: Safety Analysis Set included all participants who received tepotinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy Participants (Control) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
| Healthy Participants (Control) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | ECG Findings | 0 Participants |
| Mild Hepatic Impairment (Child-Pugh Class A) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
| Mild Hepatic Impairment (Child-Pugh Class A) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | ECG Findings | 0 Participants |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | ECG Findings | 0 Participants |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs were reported.
Time frame: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Population: Safety Analysis Set included all participants who received tepotinib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Participants (Control) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Mild Hepatic Impairment (Child-Pugh Class A) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Participants (Control) | Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 24.00 Hours |
| Healthy Participants (Control) | Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 24.00 Hours |
| Mild Hepatic Impairment (Child-Pugh Class A) | Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 24.00 Hours |
| Mild Hepatic Impairment (Child-Pugh Class A) | Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 24.00 Hours |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571109 | 54.00 Hours |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) | MSC2571107 | 30.00 Hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Population: PK Analysis Set included all participants who received a single dose of tepotinib and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could affect the PK.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Participants (Control) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib | 11 Hours |
| Mild Hepatic Impairment (Child-Pugh Class A) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib | 11.00 Hours |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib | 16.00 Hours |