Healthy
Conditions
Keywords
Healthy volunteer, Tepotinib, Mesenchymal-epithelial transition factor, Translocated promoter region
Brief summary
This is a Phase I, open label, randomized, crossover trial to investigate the relative bioavailability of tepotinib in healthy volunteers. Twenty-four volunteers will be randomized to one of the two treatment sequences: Sequence A: test, reference, Sequence B: reference, test. The reference treatment refers to the current Phase II film-coated tablet (5 \* 100 milligram (mg) tepotinib film-coated tablets) and the test treatment to the new Phase III film-coated tablet (1 \* 500 mg film-coated tepotinib tablet).
Interventions
DRUGTepotinib test (Treatment Period 1)
Subjects will be administered a single oral dose of test treatment of film-coated tepotinib tablet (1 \* 500 mg tablet) in Treatment period 1 (Day 1)
DRUGTepotinib reference (Treatment Period 2)
Followed by a 21-day washout after Treatment period 1 (Day 1), subjects will be administered a single oral dose of reference treatment of film-coated tepotinib tablet (5 \* 100 mg tablet) in Treatment period 2 (Day 22)
DRUGTepotinib reference (Treatment Period 1)
Subjects will be administered a single oral dose of reference treatment of film-coated tepotinib tablet (5 \* 100 mg tablet) in Treatment period 1 (Day 1)
DRUGTepotinib test (Treatment Period 2)
Followed by a 21-day washout after Treatment period 1 (Day 1), subjects will be administered a single oral dose of test treatment of film-coated tepotinib tablet (1 \* 500 mg tablet) in Treatment period 2 (Day 22)
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and non-fertile, healthy female volunteers, 18 to 60 years of age (both inclusive) at the time of informed consent. * Written informed consent given before any trial related activities are performed. * Body weight greater than 50 kg and a body mass index (BMI) above 18 kilogram per meter square (kg/m\^2) and below 30 kg/m\^2 (BMI = weight \[kg\]/height \[m\^2\]) at screening. * Has vital signs in the following normal range: * Oral body temperature: 35.5 to 37.5 degree celsius (°C) * Blood pressure (BP) and pulse rate after at least 5 minutes of rest, measured in the supine position: Systolic blood pressure: 90 to 150 millimeter of mercury (mm Hg); Diastolic blood pressure: 40 to 90 mm Hg * Pulse rate: 35 to 110 beats per minute (bpm) * Non-smoker (= 0 cigarettes, pipes, cigars, e-cigarettes, or others) for at least 6 months prior to screening * Women must be postmenopausal for at least 2 years, as confirmed by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) assessments performed at screening, or surgically sterile (that is, hysterectomy, oophorectomy). Pregnancy assessments will also be performed on female volunteers at screening and at admission. * Males must agree to use and to have their female partners use highly effective medically acceptable methods of contraception during the period of participation in the trial and for at least 3 months after the last treatment administration. Men must refrain from donating sperm up to 3 months after the last treatment administration. * Ability to understand the full nature and purpose of the trial, including possible risks and adverse effects; ability to cooperate with the Investigator and to comply with the requirements of the entire trial, including dietary restrictions.
Exclusion criteria
* Any condition, including findings in the medical history, physical examination or in pretrial assessments that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the volunteer in the trial or that could interfere with the trial objectives, conduct or evaluation. * Any clinically relevant abnormality in the results of the screening safety laboratory parameters. Specifically Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin, Alkaline phosphatase (ALP), amylase, and lipase must not exceed the upper limit of the normal range. * Any clinically relevant abnormality on the 12-lead electrocardiogram recording. * Positive result from virology tests for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), or human immunodeficiency virus antibody (anti-HIV 1 and 2) at screening. * History of clinically relevant renal, cardiovascular, and pulmonary disease, or endocrinology disorder. * History of clinically relevant gastrointestinal disease, in particular pancreatic disease, cholecystitis, liver diseases or hepatic dysfunction. * History of psychiatric or neurological disorders (depression, epilepsy etc.). * Known hypersensitivity to tepotinib or its excipients. * Presence or history of any serious allergy (requiring hospitalization or prolonged systemic treatment). * Presence of drug or alcohol abuse, confirmed by positive test results for drugs of abuse or alcohol or history of drug and alcohol abuse in the past 3 years. Volunteers who consume more than 14 (female volunteers) or 21 (male volunteers) units of alcohol a week (unit = 1 glass of wine (125 milliliter \[mL\]) = 1 measure of spirits = ½ pint of beer). * Loss or donation of more than 400 mL of blood within 12 weeks prior to entry into the trial. * Participation in another clinical trial within the past 60 days. * Any prescription or over the counter medication intake within 2 weeks prior to the first administration of tepotinib, including multivitamins and herbal products (St. John's wort), with the exception of acetaminophen and ibuprofen. * Consumption of enzyme inducing or inhibiting herbal drugs, fruit juices and beverages (eg, grapefruit, grapefruit juice, Seville orange, quinine \[tonic water\], star fruit), and consumption of poppy seed within 3 days prior to the first administration of the investigational medicinal product. * Excessive consumption of beverages containing xanthine (more than (\>) 5 cups of coffee a day or equivalent) or inability to stop caffeine consumption while resident in the trial site. Continued use of caffeine (less than or equal to (=\<)3 cups/day) or caffeine containing drinks or food, eg, coffee, tea, chocolate, Red Bull, or cola (1 caffeine unit is contained in the following items: 1 \[6 ounces (oz)\] cup of coffee, 2 \[12 oz\] cans of cola, 1 \[12 oz\] cup of tea, ½ \[4 oz\] cup of energy drink \[eg, Red Bull\], or 3 oz of chocolate). * Legal incapacity or limited legal capacity. * Unlikely to comply with the protocol requirements, instructions and trial related restrictions; eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial. * Volunteer is the Investigator or Sub-Investigator, research assistant, pharmacist, trial coordinator, other staff or relative thereof directly involved in the conduct of the trial. * Vulnerable volunteers (eg, persons kept in detention).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) at Concentration at or Above Lower Limit of Quantitation (LLOQ) of Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | AUC0-t was 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 | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | AUC0-inf was calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Maximum Plasma Concentration Observed (Cmax) of Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Cmax was obtained directly from the concentration versus time curve. |
| Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | t1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half. |
| Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Apparent terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. |
| Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Apparent Volume of Distribution (Vz/f) for Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule. |
| Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported. |
| Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported. |
| Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | Baseline up to end of trial (up to Day 43) | An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. |
| Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | Baseline up to end of trial (up to Day 43) | Number of subjects with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the subjects have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), RR, PR, QRS, QT and QTcB calculated by the Bazett formula. Laboratory investigation included hematology, biochemistry, urinalysis, and coagulation. |
| Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | %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 From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | AUC0-inf was calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. |
| Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Cmax was obtained directly from the concentration versus time curve. |
| Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2 | Tmax was obtained directly from the concentration versus time curve. |
Countries
Germany
Participant flow
Pre-assignment details
Overall, 65 subjects were screened for this study. Of which, 24 subjects were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1\*500 mg) or a single oral dose of reference treatment of film-coated tepotinib tablet (5\*100 mg tablet) in either Treatment Period 1 or 2. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period (21 Days) | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 10.03 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 10 / 23 | 9 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib
AUC0-inf was calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib Test Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib | 25709.6 ng*h/mL | Geometric Coefficient of Variation 29.6 |
| Tepotinib Reference Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib | 26990.3 ng*h/mL | Geometric Coefficient of Variation 26.1 |
90% CI: [88.43, 103.59]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) at Concentration at or Above Lower Limit of Quantitation (LLOQ) of Tepotinib
AUC0-t was calculated according to the mixed log linear trapezoidal rule.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The pharmacokinetic (PK) analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib Test Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) at Concentration at or Above Lower Limit of Quantitation (LLOQ) of Tepotinib | 25159.2 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| Tepotinib Reference Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) at Concentration at or Above Lower Limit of Quantitation (LLOQ) of Tepotinib | 25983.7 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 24 |
90% CI: [93.67, 103.96]
Primary
Maximum Plasma Concentration Observed (Cmax) of Tepotinib
Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib Test Treatment | Maximum Plasma Concentration Observed (Cmax) of Tepotinib | 463.0 ng/mL | Geometric Coefficient of Variation 26.2 |
| Tepotinib Reference Treatment | Maximum Plasma Concentration Observed (Cmax) of Tepotinib | 486.3 ng/mL | Geometric Coefficient of Variation 19.8 |
90% CI: [90.8, 103.36]
Primary
Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib Test Treatment | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | 8.000 hours |
| Tepotinib Reference Treatment | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | 8.000 hours |
p-value: 0.898190% CI: [-1, 1.025]Wilcoxon signed-rank test
Secondary
Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma
t1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and Number Analyzed signifies those subjects who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | Tepotinib | 35.27 hours | Geometric Coefficient of Variation 18.1 |
| Tepotinib Test Treatment | Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571109A | 47.33 hours | Geometric Coefficient of Variation 25.4 |
| Tepotinib Test Treatment | Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571107A | 42.39 hours | Geometric Coefficient of Variation 17 |
| Tepotinib Reference Treatment | Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | Tepotinib | 34.27 hours | Geometric Coefficient of Variation 22.5 |
| Tepotinib Reference Treatment | Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571109A | 46.39 hours | Geometric Coefficient of Variation 28.8 |
| Tepotinib Reference Treatment | Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571107A | 40.18 hours | Geometric Coefficient of Variation 21.3 |
Secondary
Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma
Apparent terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and Number Analyzed signifies those subjects who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | Tepotinib | 0.019652 1/h | Geometric Coefficient of Variation 18.1 |
| Tepotinib Test Treatment | Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571109A | 0.014643 1/h | Geometric Coefficient of Variation 25.4 |
| Tepotinib Test Treatment | Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571107A | 0.016350 1/h | Geometric Coefficient of Variation 17 |
| Tepotinib Reference Treatment | Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | Tepotinib | 0.020229 1/h | Geometric Coefficient of Variation 22.5 |
| Tepotinib Reference Treatment | Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571109A | 0.014942 1/h | Geometric Coefficient of Variation 28.8 |
| Tepotinib Reference Treatment | Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma | MSC2571107A | 0.017252 1/h | Geometric Coefficient of Variation 21.3 |
Secondary
Apparent Volume of Distribution (Vz/f) for Tepotinib
Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib Test Treatment | Apparent Volume of Distribution (Vz/f) for Tepotinib | 890.7 liters | Geometric Coefficient of Variation 27.7 |
| Tepotinib Reference Treatment | Apparent Volume of Distribution (Vz/f) for Tepotinib | 824.2 liters | Geometric Coefficient of Variation 21.4 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
AUC0-inf was calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and Number Analyzed signifies those subjects who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 13932.6 ng*h/mL | Geometric Coefficient of Variation 31 |
| Tepotinib Test Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 865.0 ng*h/mL | Geometric Coefficient of Variation 39.7 |
| Tepotinib Reference Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 14541.7 ng*h/mL | Geometric Coefficient of Variation 25.5 |
| Tepotinib Reference Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 830.4 ng*h/mL | Geometric Coefficient of Variation 35.6 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 13637.3 ng*h/mL | Geometric Coefficient of Variation 30.4 |
| Tepotinib Test Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 846.2 ng*h/mL | Geometric Coefficient of Variation 42.4 |
| Tepotinib Reference Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 14164.7 ng*h/mL | Geometric Coefficient of Variation 27.1 |
| Tepotinib Reference Treatment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 849.5 ng*h/mL | Geometric Coefficient of Variation 36.3 |
Secondary
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)
%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, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and Number Analyzed signifies those subjects who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | Tepotinib | 1.5025 percentage of AUC0-inf | Geometric Coefficient of Variation 36.7 |
| Tepotinib Test Treatment | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 0.4040 percentage of AUC0-inf | Geometric Coefficient of Variation 45.9 |
| Tepotinib Test Treatment | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 0.9715 percentage of AUC0-inf | Geometric Coefficient of Variation 49.1 |
| Tepotinib Reference Treatment | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | Tepotinib | 1.5394 percentage of AUC0-inf | Geometric Coefficient of Variation 44.7 |
| Tepotinib Reference Treatment | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 0.4257 percentage of AUC0-inf | Geometric Coefficient of Variation 48.1 |
| Tepotinib Reference Treatment | Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 0.9748 percentage of AUC0-inf | Geometric Coefficient of Variation 46.3 |
Secondary
Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 160.40 ng/mL | Geometric Coefficient of Variation 28.6 |
| Tepotinib Test Treatment | Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 11.630 ng/mL | Geometric Coefficient of Variation 38.2 |
| Tepotinib Reference Treatment | Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 160.86 ng/mL | Geometric Coefficient of Variation 24.4 |
| Tepotinib Reference Treatment | Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 11.299 ng/mL | Geometric Coefficient of Variation 29.9 |
Secondary
Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters
Number of subjects with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the subjects have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), RR, PR, QRS, QT and QTcB calculated by the Bazett formula. Laboratory investigation included hematology, biochemistry, urinalysis, and coagulation.
Time frame: Baseline up to end of trial (up to Day 43)
Population: SAF population. A total of 24 subjects were evaluated for adverse events. Because 1 subject in each treatment sequence discontinued before receiving the second treatment, only 23 subjects received Test Treatment and 23 subjects received Reference Treatment. Thus, number of subjects analyzed per treatment is mentioned as 23.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tepotinib Test Treatment | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | Vital Signs | 0 Participants |
| Tepotinib Test Treatment | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | ECG Values | 0 Participants |
| Tepotinib Test Treatment | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | Laboratory Values | 0 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | Vital Signs | 0 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | ECG Values | 0 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters | Laboratory Values | 0 Participants |
Secondary
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug.
Time frame: Baseline up to end of trial (up to Day 43)
Population: SAF population. A total of 24 subjects were evaluated for adverse events. Because 1 subject in each treatment sequence discontinued before receiving the second treatment, only 23 subjects received Test Treatment and 23 subjects received Reference Treatment.Thus, number of subjects analyzed per treatment is mentioned as 23.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tepotinib Test Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | TEAEs | 10 Participants |
| Tepotinib Test Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | Serious TEAEs | 0 Participants |
| Tepotinib Test Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | TEAEs Leading to Death | 0 Participants |
| Tepotinib Test Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 1 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 1 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | TEAEs | 9 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | TEAEs Leading to Death | 0 Participants |
| Tepotinib Reference Treatment | Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | Serious TEAEs | 0 Participants |
Secondary
Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib
Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and Number Analyzed signifies those subjects who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib | MSC2571109A | 0.5362 ratio | Geometric Coefficient of Variation 16.3 |
| Tepotinib Test Treatment | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib | MSC2571107A | 0.03397 ratio | Geometric Coefficient of Variation 25.9 |
| Tepotinib Reference Treatment | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib | MSC2571109A | 0.5353 ratio | Geometric Coefficient of Variation 18 |
| Tepotinib Reference Treatment | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib | MSC2571107A | 0.03216 ratio | Geometric Coefficient of Variation 22 |
Secondary
Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib
Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib Test Treatment | Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib | MSC2571109A | 0.3464 ratio | Geometric Coefficient of Variation 22.4 |
| Tepotinib Test Treatment | Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib | MSC2571107A | 0.02512 ratio | Geometric Coefficient of Variation 29 |
| Tepotinib Reference Treatment | Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib | MSC2571109A | 0.3308 ratio | Geometric Coefficient of Variation 23.4 |
| Tepotinib Reference Treatment | Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib | MSC2571107A | 0.02323 ratio | Geometric Coefficient of Variation 29.3 |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
Tmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tepotinib Test Treatment | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 24.00 hours |
| Tepotinib Test Treatment | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 24.00 hours |
| Tepotinib Reference Treatment | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571109A | 24.02 hours |
| Tepotinib Reference Treatment | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A) | MSC2571107A | 24.00 hours |
Secondary
Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib
CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2
Population: The PK analysis set included all subjects who received at least 1 dose of IMP and had at least 1 post-dose PK measurement without important protocol deviations/violations or events that could have affected the PK. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib Test Treatment | Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib | 17.503 liter/hour | Geometric Coefficient of Variation 29.6 |
| Tepotinib Reference Treatment | Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib | 16.673 liter/hour | Geometric Coefficient of Variation 26.1 |