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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003578-13 | EudraCT Number |
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This study investigated the bioequivalence of the 100 milligrams (mg) and 250 mg dose strengths of tepotinib tablet formulation 3 (TF3) when administered at the same dose under fasted condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test Treatment then Reference Treatment | Experimental | Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period. |
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| Reference Treatment then Test Treatment | Experimental | Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tepotinib 100 mg | Drug | Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in either treatment period 1 or 2. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib | Area under the plasma concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log linear trapezoidal rule (linear up/log down). | Pre-dose, 0.25, 0.50, 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 |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib | AUC0-inf was calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Cmax was obtained directly from the concentration versus time curve. | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | Tmax was obtained directly from the concentration versus time curve. | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose |
| Terminal Half-Life (t1/2) of Tepotinib |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of 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 |
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We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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Overall 42 participants were screened of which 18 participants were randomized in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | First Tepotinib Test, Then Tepotinib Reference | Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period. |
| FG001 | First Tepotinib Reference, Then Tepotinib Test | Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Day 1) |
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| Washout Period (21 Days) |
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| Treatment Period 2 (Day 22) |
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Safety Analysis Set included all participants who had received at least one dose of planned study intervention and had one subsequent safety assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) or single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 1 or 2. The treatment periods were separated by 21 days of washout period. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib | Area under the plasma concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log linear trapezoidal rule (linear up/log down). | Pharmacokinetic(PK) Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter (hr*ng/mL) | Pre-dose, 0.25, 0.50, 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 |
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Baseline and up to Day 59
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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 | Tepotinib Test Treatment | Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in either treatment period 1 or 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of 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 | Sep 5, 2019 | Jan 30, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 22, 2019 | Jan 30, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000707607 | tepotinib |
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| Tepotinib 250 mg | Drug | Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in either treatment period 1 or 2. |
|
t1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half. |
| Pre-dose, 0.25, 0.50, 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 |
| Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib | Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported. | Pre-dose, 0.25, 0.50, 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 |
| Apparent Total Body Clearance (CL/f) of Tepotinib | CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. | Baseline up to Day 59 |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Laboratory parameters included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator. | Baseline up to Day 59 |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in either treatment period 1 or 2. |
| OG001 | Tepotinib Reference Treatment | Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in either treatment period 1 or 2. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib | AUC0-inf was calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | Pre-dose, 0.25, 0.50, 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 |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Cmax was obtained directly from the concentration versus time curve. | PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose |
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| Secondary | Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib | Tmax was obtained directly from the concentration versus time curve. | PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. | Posted | Median | Full Range | Hours | Pre-dose, 0.25, 0.50, 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 |
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| Secondary | Terminal Half-Life (t1/2) of Tepotinib | 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. | PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose, 0.25, 0.50, 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 |
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|
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| Secondary | Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib | Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported. | PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Pre-dose, 0.25, 0.50, 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 |
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| Secondary | Apparent Total Body Clearance (CL/f) of Tepotinib | CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | PK Analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Pre-dose, 0.25, 0.50, 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 |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation | An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. | Safety Analysis set included all participants who had received at least one dose of planned study intervention and had one subsequent safety assessment. | Posted | Count of Participants | Participants | Baseline up to Day 59 |
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| Secondary | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs | Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Laboratory parameters included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator. | Safety Analysis set included all participants who had received at least one dose of planned study intervention and had one subsequent safety assessment. | Posted | Count of Participants | Participants | Baseline up to Day 59 |
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| 0 |
| 18 |
| 0 |
| 18 |
| 7 |
| 18 |
| EG001 | Tepotinib Reference Treatment | Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in either treatment period 1 or 2. | 0 | 18 | 0 | 18 | 6 | 18 |
| Faeces soft | Gastrointestinal disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Gingivitis | Infections and infestations | MedDRA version 22.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA version 22.1 | Non-systematic Assessment |
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| Burns first degree | Injury, poisoning and procedural complications | MedDRA version 22.1 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA version 22.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA version 22.1 | Non-systematic Assessment |
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| TEAE leading to Discontinuation |
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| TEAEs Leading to Death |
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| Vital Signs |
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