Relative Bioavailability of Two Tepotinib Film-Coated Tab... | NCT03021642

NCT03021642

ID	Type	Description	Link
2015-004369-95	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
First Tepotinib Test, Then Tepotinib Reference	Experimental		Drug: Tepotinib test (Treatment Period 1) Drug: Tepotinib reference (Treatment Period 2)
First Tepotinib Reference, Then Tepotinib Test	Experimental		Drug: Tepotinib reference (Treatment Period 1) Drug: Tepotinib test (Treatment Period 2)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Tepotinib test (Treatment Period 1)	Drug	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)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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
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.	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
Maximum Plasma Concentration Observed (Cmax) of Tepotinib	Cmax was obtained directly from the concentration versus time curve.	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) of Tepotinib	Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.	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

Secondary Outcomes

Measure	Description	Time Frame
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.	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

Eligibility Module

Eligibility Criteria

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).

Contacts/Locations Module

Name	Affiliation	Role
Medical Responsible	Merck KGaA, Darmstadt, Germany	Study Director

References Module

Label	URL
Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)	View source

ID	Title	Description
FG000	First Tepotinib Test, Then Tepotinib Reference	Subjects received a single oral dose of test treatment of film-coated tepotinib tablet (1500 milligram [mg]) in Treatment period 1 (Day 1) followed by a single oral dose of reference treatment of film-coated tepotinib tablet (5100 mg tablet) in Treatment period 2 (Day 22). A washout period of 21 days was maintained between the 2 treatment periods.

ID	Title	Description
BG000	Entire Study Population	All subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1500 mg) or a single oral dose of reference treatment of film-coated tepotinib tablet (5100 mg tablet) in either Treatment Period 1 or 2.

Units	Counts
Participants	BG00024

Categories

Title	Measurements
	OG00025159.2± 27.0 OG00125983.7± 24.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Geometric Least square (LS) mean ratio	98.68			2-Sided	90	93.67	103.96					Superiority or Other (legacy)

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Primary

Maximum Plasma Concentration Observed (Cmax) of Tepotinib

Cmax was obtained directly from the concentration versus time curve.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts
Participants

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.

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Secondary

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Secondary

Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)

Cmax was obtained directly from the concentration versus time curve.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts

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.

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts
Participants

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

1/h

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

liter/hour

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

liters

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

percentage of AUC0-inf

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

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

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Units	Counts

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.

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.

Posted

Count of Participants

Participants

Baseline up to end of trial (up to Day 43)

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment

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.

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.

Posted

Count of Participants

Participants

Baseline up to end of trial (up to Day 43)

ID	Title	Description
OG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.
OG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Tepotinib Test Treatment	Subjects who received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg tablet) in either Treatment period 1 or 2.	0	23	0	23	10	23
EG001	Tepotinib Reference Treatment	Subjects who received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in either Treatment period 1 or 2.	0	23	0	23	9	23

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthropod Bite	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Foreign Body In Eye	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Amylase Increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Lipase Increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Dry Throat	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Catheter Site Inflammation	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Catheter Site Related Reaction	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0012 affected23 at risk
Chills	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Influenza Like Illness	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0012 affected23 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Mouth Ulceration	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Toothache	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Hepatic Function Abnormal	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk
Dermatitis Contact	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected23 at risk EG0010 affected23 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0011 affected23 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected23 at risk EG0012 affected23 at risk
Influenza	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected23 at risk EG0010 affected23 at risk