Trial Outcomes & Findings for Tepotinib Hepatic Impairment Trial (NCT NCT03546608)
NCT ID: NCT03546608
Last Updated: 2024-08-12
Results Overview
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.
COMPLETED
PHASE1
18 participants
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
2024-08-12
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tepotinib Hepatic Impairment Trial
Baseline characteristics by cohort
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59 Years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
61 Years
STANDARD_DEVIATION 3.9 • n=7 Participants
|
60 Years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
60 Years
STANDARD_DEVIATION 7.3 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
26100 Nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 63.9
|
24200 Nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 26.9
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
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).
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
25600 ng*h/mL
Geometric Coefficient of Variation 65.6
|
23500 ng*h/mL
Geometric Coefficient of Variation 27.4
|
PRIMARY outcome
Timeframe: 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 1Population: 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.
Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time profile.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Tepotinib
|
406 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 12.2
|
416 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 31.5
|
288 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 23.5
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib
|
11 Hours
Interval 10.0 to 12.0
|
11.00 Hours
Interval 8.0 to 24.0
|
16.00 Hours
Interval 6.0 to 30.08
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Apparent Terminal Half Life (t1/2) of Tepotinib
|
36.8 Hours
Interval 32.3 to 48.4
|
43.7 Hours
Interval 31.3 to 55.2
|
46.1 Hours
Interval 41.9 to 74.4
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for tepotinib.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Apparent Total Body Clearance (CL/f) of Tepotinib
|
16.4 Liter per hour
Geometric Coefficient of Variation 13.4
|
17.2 Liter per hour
Geometric Coefficient of Variation 63.9
|
18.6 Liter per hour
Geometric Coefficient of Variation 26.9
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib
|
892 Liter
Geometric Coefficient of Variation 11.4
|
1050 Liter
Geometric Coefficient of Variation 45.3
|
1400 Liter
Geometric Coefficient of Variation 20.4
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
5.01 Percentage of AUC0-inf
|
3.35 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
Participant 2
|
1.06 Percentage of AUC0-inf
|
0.895 Percentage of AUC0-inf
|
3.03 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
Participant 3
|
2.14 Percentage of AUC0-inf
|
1.33 Percentage of AUC0-inf
|
1.49 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
Participant 4
|
1.22 Percentage of AUC0-inf
|
1.16 Percentage of AUC0-inf
|
1.80 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
Participant 5
|
2.45 Percentage of AUC0-inf
|
1.55 Percentage of AUC0-inf
|
1.60 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
Participant 6
|
2.08 Percentage of AUC0-inf
|
1.41 Percentage of AUC0-inf
|
3.87 Percentage of AUC0-inf
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
1.44 Percentage of AUC0-inf
|
2.05 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)
Participant 2
|
1.28 Percentage of AUC0-inf
|
0.574 Percentage of AUC0-inf
|
1.41 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)
Participant 3
|
0.737 Percentage of AUC0-inf
|
0.605 Percentage of AUC0-inf
|
1.06 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)
Participant 4
|
0.677 Percentage of AUC0-inf
|
0.470 Percentage of AUC0-inf
|
3.06 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)
Participant 5
|
1.55 Percentage of AUC0-inf
|
0.482 Percentage of AUC0-inf
|
0.522 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)
Participant 6
|
1.07 Percentage of AUC0-inf
|
0.621 Percentage of AUC0-inf
|
1.96 Percentage of AUC0-inf
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
3.69 Percentage of AUC0-inf
|
2.10 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)
Participant 2
|
0.925 Percentage of AUC0-inf
|
0.848 Percentage of AUC0-inf
|
5.68 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)
Participant 3
|
0.671 Percentage of AUC0-inf
|
0.516 Percentage of AUC0-inf
|
0.683 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)
Participant 4
|
0.639 Percentage of AUC0-inf
|
0.513 Percentage of AUC0-inf
|
3.08 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)
Participant 5
|
1.77 Percentage of AUC0-inf
|
0.731 Percentage of AUC0-inf
|
2.45 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)
Participant 6
|
0.904 Percentage of AUC0-inf
|
1.15 Percentage of AUC0-inf
|
1.97 Percentage of AUC0-inf
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
585 ng*h/mL
Geometric Coefficient of Variation 40.5
|
653 ng*h/mL
Geometric Coefficient of Variation 33.3
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib
|
7.87 ng/mL
Geometric Coefficient of Variation 25.6
|
9.32 ng/mL
Geometric Coefficient of Variation 22.5
|
7.80 ng/mL
Geometric Coefficient of Variation 22.3
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
770 Liter per hour
Geometric Coefficient of Variation 40.5
|
689 Liter per hour
Geometric Coefficient of Variation 33.3
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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).
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
11000 ng*h/mL
Geometric Coefficient of Variation 74.8
|
18100 ng*h/mL
Geometric Coefficient of Variation 80.7
|
|
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
|
1120 ng*h/mL
Geometric Coefficient of Variation 88.8
|
1050 ng*h/mL
Geometric Coefficient of Variation 70.4
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
11100 ng*h/mL
Geometric Coefficient of Variation 74.3
|
18500 ng*h/mL
Geometric Coefficient of Variation 80.9
|
|
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
|
1140 ng*h/mL
Geometric Coefficient of Variation 87.2
|
1080 ng*h/mL
Geometric Coefficient of Variation 69.2
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
Cmax was taken directly from the observed concentration-time profile.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
MSC2571109
|
143 ng/mL
Geometric Coefficient of Variation 33.9
|
132 ng/mL
Geometric Coefficient of Variation 47.3
|
165 ng/mL
Geometric Coefficient of Variation 37.9
|
|
Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
MSC2571107
|
13.9 ng/mL
Geometric Coefficient of Variation 39.2
|
14.8 ng/mL
Geometric Coefficient of Variation 55.2
|
10.1 ng/mL
Geometric Coefficient of Variation 32.1
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
MSC2571109
|
24.00 Hours
Interval 24.0 to 48.0
|
24.00 Hours
Interval 24.0 to 48.0
|
54.00 Hours
Interval 24.0 to 72.0
|
|
Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
MSC2571107
|
24.00 Hours
Interval 24.0 to 30.0
|
24.00 Hours
Interval 24.0 to 24.0
|
30.00 Hours
Interval 16.0 to 72.0
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
MSC2571109
|
46.3 Hours
Interval 43.9 to 56.4
|
57.5 Hours
Interval 32.9 to 67.5
|
78.8 Hours
Interval 55.5 to 128.0
|
|
Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
MSC2571107
|
46.8 Hours
Interval 43.8 to 58.6
|
40.7 Hours
Interval 33.9 to 69.8
|
75.4 Hours
Interval 53.3 to 137.0
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
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
|
0.424 Ratio
Geometric Coefficient of Variation 24.7
|
0.764 Ratio
Geometric Coefficient of Variation 49.5
|
|
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
|
0.0435 Ratio
Geometric Coefficient of Variation 32.3
|
0.0449 Ratio
Geometric Coefficient of Variation 40.0
|
SECONDARY outcome
Timeframe: 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 1Population: 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.
Cmax was taken directly from the observed concentration-time profile. Ratio of Cmax of Metabolite (MSC2571109 or MSC2571107) to Cmax of tepotinib was reported.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio
MSC2571109
|
0.353 Ratio
Geometric Coefficient of Variation 27.5
|
0.318 Ratio
Geometric Coefficient of Variation 30.0
|
0.571 Ratio
Geometric Coefficient of Variation 37.3
|
|
Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio
MSC2571107
|
0.0343 Ratio
Geometric Coefficient of Variation 29.2
|
0.0357 Ratio
Geometric Coefficient of Variation 32.9
|
0.0351 Ratio
Geometric Coefficient of Variation 27.1
|
SECONDARY outcome
Timeframe: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22Population: Safety Analysis Set included all participants who received tepotinib.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
1 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22Population: Safety Analysis Set included all participants who received tepotinib.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22Population: Safety Analysis Set included all participants who received tepotinib.
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.
Outcome measures
| Measure |
Healthy Participants (Control)
n=6 Participants
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 Participants
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings
Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings
ECG Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Healthy Participants (Control)
Mild Hepatic Impairment (Child-Pugh Class A)
Moderate Hepatic Impairment (Child-Pugh Class B)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Healthy Participants (Control)
n=6 participants at risk
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.
|
Mild Hepatic Impairment (Child-Pugh Class A)
n=6 participants at risk
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.
|
Moderate Hepatic Impairment (Child-Pugh Class B)
n=6 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
0.00%
0/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
0.00%
0/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
|
Infections and infestations
Ear infection
|
0.00%
0/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
0.00%
0/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
16.7%
1/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
0.00%
0/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
16.7%
1/6 • For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER