Healthy
Conditions
Keywords
Proton Pump Inhibitor, Omeprazole, Tepotinib, Non-small cell lung cancer (NSCLC), Pharmacokinetics
Brief summary
This study was investigated in healthy participants (i) the effect of omeprazole (proton pump inhibitor) co-administration on the single dose pharmacokinetics (PK) of tepotinib under fed conditions, and (ii) the effect of food on the single dose PK of tepotinib after co-administration of omeprazole and tepotinib. Furthermore, the study assessed the safety and tolerability of tepotinib alone and upon co-administration of omeprazole.
Interventions
DRUGTepotinib
Participants received single oral dose of 500 mg Tepotinib in Treatment A, B and C.
DRUGOmeprazole
Participants received omeprazole alone on Day 1 to 4 and co-administration of omeprazole with Tepotinib on Day 5 in Treatment B and C.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants of non-child bearing potential * Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m\^2) * Body weight between 50 to 100 kilogram (kg) * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participation in a clinical study within 60 days prior to first drug administration * Whole blood donation or loss of greater than (\>) 450 milliliter (mL) within 60 days prior to first drug administration * Any surgical or medical condition, or any other significant disease that could interfere with the study objectives, conduct, or evaluation * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C) | Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C) | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/Lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. |
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C) | Cmax was obtained directly from the concentration versus time curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C) | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C) | Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. |
| Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C) | Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B | Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. |
| Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C) | Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether/not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs. |
| Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and C | The laboratory measurements included hematology, biochemistry, virology, drugs of abuse, hormones, and urinalysis. ECG recordings included PR, QRS, RR, QT and corrected QT intervals (QTcF). Vital sign assessment included blood pressure, pulse rate, body temperature. Number of participants with clinically significant abnormalities in laboratory parameters, 12-lead ECG findings, vital signs were reported. Clinically significance was decided by investigator. |
| Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/Lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. |
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B | Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B | Cmax was obtained directly from the concentration versus time curve. |
Countries
Germany
Participant flow
Pre-assignment details
Overall, 28 participants were screened for the study. Out of which 12 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants who received single oral dose of 500 mg of Tepotinib alone in fed state (Treatment A) or in fasted state with 40 mg omeprazole (Treatment B) or in fed state with 40 mg omeprazole (Treatment C) in either Treatment period 1, Treatment Period 2 or Treatment period 3. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 48 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 12 | 3 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/Lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C | 23081 h*ng/mL | Geometric Coefficient of Variation 19.8 |
| Treatment C | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C | 25343 h*ng/mL | Geometric Coefficient of Variation 21.3 |
90% CI: [101.69, 118.55]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
Population: Pharmacokinetic (PK) Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C | 21722 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 18.3 |
| Treatment C | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C | 23649 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.5 |
90% CI: [101.2, 117.13]
Primary
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C | 428 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12.2 |
| Treatment C | Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C | 445 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21.1 |
90% CI: [92.93, 116.61]
Secondary
Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C | 32.9 hour |
| Treatment C | Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C | 30.7 hour |
| Treatment C | Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C | 31.7 hour |
Secondary
Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C | 19.5 Liter per hour (L/h) | Geometric Coefficient of Variation 19.8 |
| Treatment C | Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C | 25.8 Liter per hour (L/h) | Geometric Coefficient of Variation 27.2 |
| Treatment C | Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C | 17.8 Liter per hour (L/h) | Geometric Coefficient of Variation 21.3 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C | 912 Liters | Geometric Coefficient of Variation 18.4 |
| Treatment C | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C | 1181 Liters | Geometric Coefficient of Variation 21.7 |
| Treatment C | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C | 860 Liters | Geometric Coefficient of Variation 21.9 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/Lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B | 17412 h*ng/mL | Geometric Coefficient of Variation 27.2 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B | 16220 h*ng/mL | Geometric Coefficient of Variation 24.4 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B
Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B
Population: PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B | 227 ng/mL | Geometric Coefficient of Variation 25.7 |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
The laboratory measurements included hematology, biochemistry, virology, drugs of abuse, hormones, and urinalysis. ECG recordings included PR, QRS, RR, QT and corrected QT intervals (QTcF). Vital sign assessment included blood pressure, pulse rate, body temperature. Number of participants with clinically significant abnormalities in laboratory parameters, 12-lead ECG findings, vital signs were reported. Clinically significance was decided by investigator.
Time frame: Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and C
Population: The Safety Analysis Set included all participants who received at least 1 dose of planned IMP and had 1 subsequent safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Laboratory Parameters | 0 Participants |
| Treatment A | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Treatment A | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Vital Signs | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Vital Signs | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Laboratory Parameters | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Laboratory Parameters | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Vital Signs | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether/not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs.
Time frame: Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
Population: The Safety Analysis Set included all participants who received at least 1 dose of planned IMP and had 1 subsequent safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Treatment C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Treatment C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C
Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
Population: None of the participants were analyzed and no data was collected for this outcome as Tlag was included in the Statistical Analysis Plan and protocol in error and this parameter was not relevant for decision making. Hence, no analysis was conducted for this outcome.
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C | 8.0 Hours |
| Treatment C | Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C | 12.0 Hours |
| Treatment C | Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C | 8.0 Hours |