<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03021642</url>
  </required_header>
  <id_info>
    <org_study_id>MS200095-0012</org_study_id>
    <secondary_id>2015-004369-95</secondary_id>
    <nct_id>NCT03021642</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability of Two Tepotinib Film-Coated Tablet Formulations in Healthy Volunteers</brief_title>
  <official_title>A Phase I, Open-label, Randomized, Cross-over Trial to Investigate the Relative Bioavailability of Two Tepotinib Film-Coated Tablet Formulations in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I, open label, randomized, crossover trial to investigate the relative&#xD;
      bioavailability of tepotinib in healthy volunteers. Twenty-four volunteers will be randomized&#xD;
      to one of the two treatment sequences: Sequence A: test, reference, Sequence B: reference,&#xD;
      test. The reference treatment refers to the current Phase II film-coated tablet (5 * 100&#xD;
      milligram (mg) tepotinib film-coated tablets) and the test treatment to the new Phase III&#xD;
      film-coated tablet (1 * 500 mg film-coated tepotinib tablet).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2016</start_date>
  <completion_date type="Actual">March 31, 2016</completion_date>
  <primary_completion_date type="Actual">March 31, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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</measure>
    <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</time_frame>
    <description>AUC0-t was calculated according to the mixed log linear trapezoidal rule.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib</measure>
    <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</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration Observed (Cmax) of Tepotinib</measure>
    <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</time_frame>
    <description>Cmax was obtained directly from the concentration versus time curve.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib</measure>
    <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</time_frame>
    <description>Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</measure>
    <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</time_frame>
    <description>AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</measure>
    <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</time_frame>
    <description>Cmax was obtained directly from the concentration versus time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</measure>
    <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</time_frame>
    <description>Tmax was obtained directly from the concentration versus time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/f) for Tepotinib</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)</measure>
    <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</time_frame>
    <description>%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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <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</time_frame>
    <description>Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib</measure>
    <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</time_frame>
    <description>Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation</measure>
    <time_frame>Baseline up to end of trial (up to Day 43)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters</measure>
    <time_frame>Baseline up to end of trial (up to Day 43)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>First Tepotinib Test, Then Tepotinib Reference</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>First Tepotinib Reference, Then Tepotinib Test</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tepotinib test (Treatment Period 1)</intervention_name>
    <description>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)</description>
    <arm_group_label>First Tepotinib Test, Then Tepotinib Reference</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tepotinib reference (Treatment Period 2)</intervention_name>
    <description>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)</description>
    <arm_group_label>First Tepotinib Test, Then Tepotinib Reference</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tepotinib reference (Treatment Period 1)</intervention_name>
    <description>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)</description>
    <arm_group_label>First Tepotinib Reference, Then Tepotinib Test</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tepotinib test (Treatment Period 2)</intervention_name>
    <description>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)</description>
    <arm_group_label>First Tepotinib Reference, Then Tepotinib Test</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and non-fertile, healthy female volunteers, 18 to 60 years of age (both&#xD;
             inclusive) at the time of informed consent.&#xD;
&#xD;
          -  Written informed consent given before any trial related activities are performed.&#xD;
&#xD;
          -  Body weight greater than 50 kg and a body mass index (BMI) above 18 kilogram per meter&#xD;
             square (kg/m^2) and below 30 kg/m^2 (BMI = weight [kg]/height [m^2]) at screening.&#xD;
&#xD;
          -  Has vital signs in the following normal range:&#xD;
&#xD;
               -  Oral body temperature: 35.5 to 37.5 degree celsius (°C)&#xD;
&#xD;
               -  Blood pressure (BP) and pulse rate after at least 5 minutes of rest, measured in&#xD;
                  the supine position: Systolic blood pressure: 90 to 150 millimeter of mercury (mm&#xD;
                  Hg); Diastolic blood pressure: 40 to 90 mm Hg&#xD;
&#xD;
               -  Pulse rate: 35 to 110 beats per minute (bpm)&#xD;
&#xD;
          -  Non-smoker (= 0 cigarettes, pipes, cigars, e-cigarettes, or others) for at least 6&#xD;
             months prior to screening&#xD;
&#xD;
          -  Women must be postmenopausal for at least 2 years, as confirmed by luteinizing hormone&#xD;
             (LH) and follicle-stimulating hormone (FSH) assessments performed at screening, or&#xD;
             surgically sterile (that is, hysterectomy, oophorectomy). Pregnancy assessments will&#xD;
             also be performed on female volunteers at screening and at admission.&#xD;
&#xD;
          -  Males must agree to use and to have their female partners use highly effective&#xD;
             medically acceptable methods of contraception during the period of participation in&#xD;
             the trial and for at least 3 months after the last treatment administration. Men must&#xD;
             refrain from donating sperm up to 3 months after the last treatment administration.&#xD;
&#xD;
          -  Ability to understand the full nature and purpose of the trial, including possible&#xD;
             risks and adverse effects; ability to cooperate with the Investigator and to comply&#xD;
             with the requirements of the entire trial, including dietary restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any condition, including findings in the medical history, physical examination or in&#xD;
             pretrial assessments that in the opinion of the Investigator, constitutes a risk or a&#xD;
             contraindication for the participation of the volunteer in the trial or that could&#xD;
             interfere with the trial objectives, conduct or evaluation.&#xD;
&#xD;
          -  Any clinically relevant abnormality in the results of the screening safety laboratory&#xD;
             parameters. Specifically Alanine transaminase (ALT), aspartate aminotransferase (AST),&#xD;
             total bilirubin, Alkaline phosphatase (ALP), amylase, and lipase must not exceed the&#xD;
             upper limit of the normal range.&#xD;
&#xD;
          -  Any clinically relevant abnormality on the 12-lead electrocardiogram recording.&#xD;
&#xD;
          -  Positive result from virology tests for hepatitis B surface antigen (HBsAg), hepatitis&#xD;
             C virus antibody (anti-HCV), or human immunodeficiency virus antibody (anti-HIV 1 and&#xD;
             2) at screening.&#xD;
&#xD;
          -  History of clinically relevant renal, cardiovascular, and pulmonary disease, or&#xD;
             endocrinology disorder.&#xD;
&#xD;
          -  History of clinically relevant gastrointestinal disease, in particular pancreatic&#xD;
             disease, cholecystitis, liver diseases or hepatic dysfunction.&#xD;
&#xD;
          -  History of psychiatric or neurological disorders (depression, epilepsy etc.).&#xD;
&#xD;
          -  Known hypersensitivity to tepotinib or its excipients.&#xD;
&#xD;
          -  Presence or history of any serious allergy (requiring hospitalization or prolonged&#xD;
             systemic treatment).&#xD;
&#xD;
          -  Presence of drug or alcohol abuse, confirmed by positive test results for drugs of&#xD;
             abuse or alcohol or history of drug and alcohol abuse in the past 3 years. Volunteers&#xD;
             who consume more than 14 (female volunteers) or 21 (male volunteers) units of alcohol&#xD;
             a week (unit = 1 glass of wine (125 milliliter [mL]) = 1 measure of spirits = ½ pint&#xD;
             of beer).&#xD;
&#xD;
          -  Loss or donation of more than 400 mL of blood within 12 weeks prior to entry into the&#xD;
             trial.&#xD;
&#xD;
          -  Participation in another clinical trial within the past 60 days.&#xD;
&#xD;
          -  Any prescription or over the counter medication intake within 2 weeks prior to the&#xD;
             first administration of tepotinib, including multivitamins and herbal products (St.&#xD;
             John's wort), with the exception of acetaminophen and ibuprofen.&#xD;
&#xD;
          -  Consumption of enzyme inducing or inhibiting herbal drugs, fruit juices and beverages&#xD;
             (eg, grapefruit, grapefruit juice, Seville orange, quinine [tonic water], star fruit),&#xD;
             and consumption of poppy seed within 3 days prior to the first administration of the&#xD;
             investigational medicinal product.&#xD;
&#xD;
          -  Excessive consumption of beverages containing xanthine (more than (&gt;) 5 cups of coffee&#xD;
             a day or equivalent) or inability to stop caffeine consumption while resident in the&#xD;
             trial site. Continued use of caffeine (less than or equal to (=&lt;)3 cups/day) or&#xD;
             caffeine containing drinks or food, eg, coffee, tea, chocolate, Red Bull, or cola (1&#xD;
             caffeine unit is contained in the following items: 1 [6 ounces (oz)] cup of coffee, 2&#xD;
             [12 oz] cans of cola, 1 [12 oz] cup of tea, ½ [4 oz] cup of energy drink [eg, Red&#xD;
             Bull], or 3 oz of chocolate).&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity.&#xD;
&#xD;
          -  Unlikely to comply with the protocol requirements, instructions and trial related&#xD;
             restrictions; eg, uncooperative attitude, inability to return for follow-up visits,&#xD;
             and improbability of completing the trial.&#xD;
&#xD;
          -  Volunteer is the Investigator or Sub-Investigator, research assistant, pharmacist,&#xD;
             trial coordinator, other staff or relative thereof directly involved in the conduct of&#xD;
             the trial.&#xD;
&#xD;
          -  Vulnerable volunteers (eg, persons kept in detention).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>For Recruiting Locations outside US, please Contact Merck KGaA Communication Center</name>
      <address>
        <city>Darmstadt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>https://clinical-information.canada.ca/ci-rc/item/242300</url>
    <description>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)</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <results_first_submitted>August 23, 2018</results_first_submitted>
  <results_first_submitted_qc>August 23, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">January 25, 2019</results_first_posted>
  <last_update_submitted>August 22, 2022</last_update_submitted>
  <last_update_submitted_qc>August 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy volunteer</keyword>
  <keyword>Tepotinib</keyword>
  <keyword>Mesenchymal-epithelial transition factor</keyword>
  <keyword>Translocated promoter region</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tepotinib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Overall, 65 subjects were screened for this study. Of which, 24 subjects were randomized into the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>First Tepotinib Test, Then Tepotinib Reference</title>
          <description>Subjects received a single oral dose of test treatment of film-coated tepotinib tablet (1*500 milligram [mg]) in Treatment period 1 (Day 1) followed by a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in Treatment period 2 (Day 22). A washout period of 21 days was maintained between the 2 treatment periods.</description>
        </group>
        <group group_id="P2">
          <title>First Tepotinib Reference, Then Tepotinib Test</title>
          <description>Subjects received a single oral dose of reference treatment of film-coated tepotinib tablet (5*100 mg tablet) in Treatment period 1 (Day 1) followed by a single oral dose of test treatment of film-coated tepotinib tablet (1*500 mg) in Treatment period 2 (Day 22). A washout period of 21 days was maintained between the 2 treatment periods.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1 (Day 1)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period (21 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Treatment Period 2 (Day 22)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set (SAF) included all subjects who received at least one dose of the Investigational Medicinal Product (IMP) and had follow up safety data.</population>
      <group_list>
        <group group_id="B1">
          <title>Entire Study Population</title>
          <description>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.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.8" spread="10.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>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</title>
        <description>AUC0-t was calculated according to the mixed log linear trapezoidal rule.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>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</title>
          <description>AUC0-t was calculated according to the mixed log linear trapezoidal rule.</description>
          <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.</population>
          <units>nanograms*hour per milliliter (ng*h/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25159.2" spread="27.0"/>
                    <measurement group_id="O2" value="25983.7" spread="24.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Geometric Least square (LS) mean ratio</param_type>
            <param_value>98.68</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>93.67</ci_lower_limit>
            <ci_upper_limit>103.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib</title>
        <description>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.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib</title>
          <description>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.</description>
          <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.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25709.6" spread="29.6"/>
                    <measurement group_id="O2" value="26990.3" spread="26.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Geometric LS mean ratio</param_type>
            <param_value>95.71</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>88.43</ci_lower_limit>
            <ci_upper_limit>103.59</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration Observed (Cmax) of Tepotinib</title>
        <description>Cmax was obtained directly from the concentration versus time curve.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration Observed (Cmax) of Tepotinib</title>
          <description>Cmax was obtained directly from the concentration versus time curve.</description>
          <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.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="463.0" spread="26.2"/>
                    <measurement group_id="O2" value="486.3" spread="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Geometric LS mean ratio</param_type>
            <param_value>96.88</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>90.8</ci_lower_limit>
            <ci_upper_limit>103.36</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib</title>
        <description>Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib</title>
          <description>Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.</description>
          <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.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.000" lower_limit="4.00" upper_limit="24.00"/>
                    <measurement group_id="O2" value="8.000" lower_limit="4.00" upper_limit="16.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.8981</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>0.000</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.000</ci_lower_limit>
            <ci_upper_limit>1.025</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
        <description>AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
          <description>AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule.</description>
          <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.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSC2571109A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13637.3" spread="30.4"/>
                    <measurement group_id="O2" value="14164.7" spread="27.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="846.2" spread="42.4"/>
                    <measurement group_id="O2" value="849.5" spread="36.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
        <description>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.</description>
        <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</time_frame>
        <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
          <description>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.</description>
          <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSC2571109A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13932.6" spread="31.0"/>
                    <measurement group_id="O2" value="14541.7" spread="25.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="865.0" spread="39.7"/>
                    <measurement group_id="O2" value="830.4" spread="35.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
        <description>Cmax was obtained directly from the concentration versus time curve.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
          <description>Cmax was obtained directly from the concentration versus time curve.</description>
          <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.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSC2571109A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="160.40" spread="28.6"/>
                    <measurement group_id="O2" value="160.86" spread="24.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.630" spread="38.2"/>
                    <measurement group_id="O2" value="11.299" spread="29.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
        <description>Tmax was obtained directly from the concentration versus time curve.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)</title>
          <description>Tmax was obtained directly from the concentration versus time curve.</description>
          <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.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSC2571109A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.00" lower_limit="24.0" upper_limit="48.0"/>
                    <measurement group_id="O2" value="24.02" lower_limit="24.0" upper_limit="97.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.00" lower_limit="16.0" upper_limit="48.0"/>
                    <measurement group_id="O2" value="24.00" lower_limit="16.0" upper_limit="48.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma</title>
        <description>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.</description>
        <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</time_frame>
        <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma</title>
          <description>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.</description>
          <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tepotinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.27" spread="18.1"/>
                    <measurement group_id="O2" value="34.27" spread="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571109A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.33" spread="25.4"/>
                    <measurement group_id="O2" value="46.39" spread="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.39" spread="17.0"/>
                    <measurement group_id="O2" value="40.18" spread="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma</title>
        <description>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.</description>
        <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</time_frame>
        <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma</title>
          <description>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.</description>
          <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
          <units>1/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tepotinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.019652" spread="18.1"/>
                    <measurement group_id="O2" value="0.020229" spread="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571109A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.014643" spread="25.4"/>
                    <measurement group_id="O2" value="0.014942" spread="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.016350" spread="17.0"/>
                    <measurement group_id="O2" value="0.017252" spread="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib</title>
        <description>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.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib</title>
          <description>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.</description>
          <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.</population>
          <units>liter/hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.503" spread="29.6"/>
                    <measurement group_id="O2" value="16.673" spread="26.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution (Vz/f) for Tepotinib</title>
        <description>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.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution (Vz/f) for Tepotinib</title>
          <description>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.</description>
          <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.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="890.7" spread="27.7"/>
                    <measurement group_id="O2" value="824.2" spread="21.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)</title>
        <description>%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.</description>
        <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</time_frame>
        <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)</title>
          <description>%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.</description>
          <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
          <units>percentage of AUC0-inf</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tepotinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5025" spread="36.7"/>
                    <measurement group_id="O2" value="1.5394" spread="44.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571109A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4040" spread="45.9"/>
                    <measurement group_id="O2" value="0.4257" spread="48.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9715" spread="49.1"/>
                    <measurement group_id="O2" value="0.9748" spread="46.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>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</title>
        <description>Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported.</description>
        <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</time_frame>
        <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>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</title>
          <description>Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported.</description>
          <population>The PK analysis set. Here 'Overall number of participants analyzed' = overall number of subjects evaluable for this outcome measure and &quot;Number Analyzed&quot; signifies those subjects who were evaluable for specified category.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSC2571109A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5362" spread="16.3"/>
                    <measurement group_id="O2" value="0.5353" spread="18.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03397" spread="25.9"/>
                    <measurement group_id="O2" value="0.03216" spread="22.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib</title>
        <description>Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported.</description>
        <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</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib</title>
          <description>Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported.</description>
          <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.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MSC2571109A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3464" spread="22.4"/>
                    <measurement group_id="O2" value="0.3308" spread="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MSC2571107A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02512" spread="29.0"/>
                    <measurement group_id="O2" value="0.02323" spread="29.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation</title>
        <description>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.</description>
        <time_frame>Baseline up to end of trial (up to Day 43)</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation</title>
          <description>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.</description>
          <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.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters</title>
        <description>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.</description>
        <time_frame>Baseline up to end of trial (up to Day 43)</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Tepotinib Test Treatment</title>
            <description>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.</description>
          </group>
          <group group_id="O2">
            <title>Tepotinib Reference Treatment</title>
            <description>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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters</title>
          <description>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.</description>
          <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.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Vital Signs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECG Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Laboratory Values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to end of trial (up to Day 43)</time_frame>
      <desc>The safety analysis set included all subjects who received at least 1 dose of the IMP and had follow up safety data. 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.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tepotinib Test Treatment</title>
          <description>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.</description>
        </group>
        <group group_id="E2">
          <title>Tepotinib Reference Treatment</title>
          <description>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.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Mouth Ulceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter Site Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Catheter Site Related Reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Influenza Like Illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Function Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod Bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Foreign Body In Eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Amylase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lipase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis Contact</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Any publications and presentations of the results (abstracts in journals or newspapers, oral presentations, etc.), either in whole or in part, by Investigators or their representatives will require review by the Sponsor before submission. The Sponsor will not suppress publication, but maintains the right to delay publication in order to protect intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Merck KGaA Communication Center</name_or_title>
      <organization>Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany</organization>
      <phone>+49-6151-72-5200</phone>
      <email>service@merckgroup.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03021642
org study id: MS200095-0012
secondary id: 2015-004369-95
nct id: NCT03021642
lead sponsor: 
has dmc: No
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).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 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
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
description: AUC0-t was calculated according to the mixed log linear trapezoidal rule.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib
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
description: 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.
measure: Maximum Plasma Concentration Observed (Cmax) of Tepotinib
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
description: Cmax was obtained directly from the concentration versus time curve.
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib
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
description: Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
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
description: AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
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
description: 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.
measure: Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
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
description: Cmax was obtained directly from the concentration versus time curve.
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
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
description: Tmax was obtained directly from the concentration versus time curve.
measure: Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma
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
description: 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.
measure: Apparent Terminal Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma
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
description: 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.
measure: Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib
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
description: 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.
measure: Apparent Volume of Distribution (Vz/f) for Tepotinib
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
description: 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.
measure: Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)
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
description: %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.
measure: 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
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
description: Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported.
measure: Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib
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
description: Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported.
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
time frame: Baseline up to end of trial (up to Day 43)
description: 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.
measure: Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters
time frame: Baseline up to end of trial (up to Day 43)
description: 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.
arm group label: First Tepotinib Test, Then Tepotinib Reference
arm group type: Experimental
arm group label: First Tepotinib Reference, Then Tepotinib Test
arm group type: Experimental
intervention type: Drug
intervention name: Tepotinib test (Treatment Period 1)
description: 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)
arm group label: First Tepotinib Test, Then Tepotinib Reference
intervention type: Drug
intervention name: Tepotinib reference (Treatment Period 2)
description: 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)
arm group label: First Tepotinib Test, Then Tepotinib Reference
intervention type: Drug
intervention name: Tepotinib reference (Treatment Period 1)
description: 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)
arm group label: First Tepotinib Reference, Then Tepotinib Test
intervention type: Drug
intervention name: Tepotinib test (Treatment Period 2)
description: 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)
arm group label: First Tepotinib Reference, Then Tepotinib Test
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Responsible
role: Study Director
affiliation: Merck KGaA, Darmstadt, Germany
facility: 
country: Germany
url: https://clinical-information.canada.ca/ci-rc/item/242300
description: 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)
responsible party type: Sponsor
mesh term: Tepotinib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 