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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-005056-29 | EudraCT Number |
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The main purpose of the study was to demonstrate bioequivalence between the new tablet formulation (TF3, test treatment) and the tablet formulation used in clinical studies (TF2, reference treatment) and to investigate effect of food on pharmacokinetics (PK) of tepotinib.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: First Tepotinib TF2 then TF3 | Experimental | Participants received a single oral dose of 500 milligrams (mg) Tepotinib tablet formulation 2 (TF2, reference treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib tablet formulation 3 (TF3, test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
|
| Part A: First Tepotinib TF3 then TF2 | Experimental | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
|
| Part B: First Tepotinib TF2 Fasted then TF2 Fed | Experimental | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period. |
|
| Part B: First Tepotinib TF2 Fed then TF2 Fasted | Experimental | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tepotinib TF2 | Drug | Participants received a single oral dose of 500 mg Tepotinib TF2 under fasting or fed conditions in treatment period 1 or 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Tepotinib | Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
| Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
| Part A, B and C: Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Cmax was obtained directly from the concentration versus time curve. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Part A, B and C: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nuvisan GmbH | Neu-Ulm | 89231 | Germany |
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| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
| Medical Information Location Map - Med Info Contacts | View source |
| 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) |
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Overall 142 participants were screened in this study. Out of which 66 participants were randomized into the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: First Tepotinib TF2 Then TF3 | Participants received a single oral dose of 500 milligrams (mg) Tepotinib tablet formulation 2 (TF2, reference treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib tablet formulation 3 (TF3, test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
| FG001 | Part A: First Tepotinib TF3 Then TF2 | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
| FG002 | Part B: First Tepotinib TF2 Fasted Then TF2 Fed | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period. |
| FG003 | Part B: First Tepotinib TF2 Fed Then TF2 Fasted | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
| FG004 | Part C: First Tepotinib TF3 Fasted Then TF3 Fed | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period. |
| FG005 | Part C: First Tepotinib TF3 Fed Then TF3 Fasted | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (21 Days) |
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| ||||||||||||||||||
| Treatment Period 2 (21 Days) |
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The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: All Participants | All participants who received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) (1*500 mg) or a single oral dose of Tepotinib TF3 (test treatment) (2*250 mg tablet) on Day 1 of either treatment period 1 or 2 under fasted conditions. |
| BG001 | Part B: All Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Tepotinib | Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. | Pharmacokinetic.(PK) Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hour per milliliter (ng*h/mL) | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
Time from date of informed consent signature up to end of study (assessed up to 7 weeks)
The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: TF2, Fasted | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye pain | Eye disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 29, 2018 | Sep 6, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 5, 2018 | Sep 6, 2022 | SAP_001.pdf |
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|
| Part C: First Tepotinib TF3 Fasted then TF3 Fed | Experimental | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period. |
|
| Part C: First Tepotinib TF3 Fed then TF3 Fasted | Experimental | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period. |
|
| Tepotinib TF3 | Drug | Participants received single oral dose of 500 mg (2 x 250 mg)Tepotinib TF3 under fasting or fed conditions in treatment period 1 or 2. |
|
| Part A, B and C: Terminal Half-Life (t1/2) of Tepotinib | Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Lambda z is the terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
| Part A, B and C: Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f) | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
| Part A, B and C: Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (Vz/f) | Vz/f was 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. Apparent volume of distribution after oral dose (Vz/f) is influenced by the fraction absorbed and was 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 after oral dose is influenced by the fraction absorbed. | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs. | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Values | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator. | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
| Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator. | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Vital sign assessment included blood pressure, pulse rate and body temperature. Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator. | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
| View source |
| Lost to Follow-up |
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| Benzodiazepines positive |
|
| Toothache treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
All participants who received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or 2 under fasted or fed conditions. |
| BG002 | Part C: All Participants | All participants who received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or 2 under fasted or fed conditions. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Part A: TF2, Fasted |
Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions. |
| OG001 | Part A: TF3, Fasted | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions. |
| OG002 | Part B: TF2, Fasted | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions. |
| OG003 | Part B: TF2, Fed | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions. |
| OG004 | Part C: TF3, Fasted | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions. |
| OG005 | Part C: TF3, Fed | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions. |
|
|
|
| Primary | Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. | PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
|
|
|
| Primary | Part A, B and C: Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Cmax was obtained directly from the concentration versus time curve. | PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
|
|
|
| Secondary | Part A, B and C: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Median | Full Range | hours | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
|
|
| Secondary | Part A, B and C: Terminal Half-Life (t1/2) of Tepotinib | Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. Lambda z is the terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. | PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
|
|
| Secondary | Part A, B and C: Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f) | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
|
|
| Secondary | Part A, B and C: Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (Vz/f) | Vz/f was 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. Apparent volume of distribution after oral dose (Vz/f) is influenced by the fraction absorbed and was 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 after oral dose is influenced by the fraction absorbed. | PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs. | The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts. | Posted | Count of Participants | Participants | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in Laboratory Values | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator. | The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts. | Posted | Count of Participants | Participants | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator. | The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts. | Posted | Count of Participants | Participants | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in Vital Signs | Vital sign assessment included blood pressure, pulse rate and body temperature. Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator. | The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts. | Posted | Count of Participants | Participants | Time from date of informed consent signature up to end of study (assessed up to 7 weeks) |
|
|
|
| 0 |
| 38 |
| 0 |
| 38 |
| 18 |
| 38 |
| EG001 | Part A: TF3, Fasted | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions. | 0 | 40 | 0 | 40 | 14 | 40 |
| EG002 | Part B: TF2, Fasted | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions. | 0 | 12 | 0 | 12 | 5 | 12 |
| EG003 | Part B: TF2, Fed | Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions. | 0 | 14 | 1 | 14 | 9 | 14 |
| EG004 | Part C: TF3, Fasted | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions. | 0 | 12 | 0 | 12 | 6 | 12 |
| EG005 | Part C: TF3, Fed | Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions. | 0 | 12 | 0 | 12 | 6 | 12 |
| Visual impairment | Eye disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Abnormal faeces | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Faeces soft | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Chest injury | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Radisectomy | Surgical and medical procedures | MedDRA 21.0 | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Catheter site related reaction | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Catheter site swelling | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA 21.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 21.0 | Non-systematic Assessment |
|
Not provided
Not provided
| Percentage of ratio of Geometric LS-Mean |
| 186.67 |
| 2-Sided |
| 90 |
| 163.78 |
| 212.77 |
| Other |
| Percentage of ratio of Geometric LS-Mean | 163.26 | 2-Sided | 90 | 146.09 | 182.46 | Other |
| Percentage of ratio of Geometric LS-Mean |
| 236.51 |
| 2-Sided |
| 90 |
| 215.69 |
| 259.34 |
| Other |
| Percentage of ratio of Geometric LS-Mean | 199.61 | 2-Sided | 90 | 176.44 | 225.82 | Other |
| Participants with Serious TEAEs |
|