Bioequivalence of 5 Tablets of 100 mg Versus 2 Tablets of 250 mg TF3 of Tepotinib

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label, Single-dose, Randomized, 2-period, 2-sequence Cross-over, Single-center Phase I Trial in Healthy Subjects to Assess the Bioequivalence of Tepotinib TF3 Administered as 5 Tablets of 100 mg Versus 2 Tablets of 250 mg Dose Strength

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tepotinib 100 mg
* Drug: Tepotinib 250 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants of non-child bearing potential Body weight between 50 to 100 kilogram (kg) Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m^2) Other protocol defined inclusion criteria could apply Exclusion Criteria: Participation in a clinical study within 60 days prior to first drug administration Whole blood donation or loss of greater than 450 milliliter (mL) within 60 days prior to first drug administration Any surgical or medical condition, or any other significant disease that could interfere with the study objectives, conduct, or evaluation Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Treatment then Reference Treatment<br>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. | Drug: Tepotinib 100 mg<br>* Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in either treatment period 1 or 2.<br>Drug: Tepotinib 250 mg<br>* Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in either treatment period 1 or 2.<br>|
| Experimental: Reference Treatment then Test Treatment<br>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. | Drug: Tepotinib 100 mg<br>* Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in either treatment period 1 or 2.<br>Drug: Tepotinib 250 mg<br>* Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in either treatment period 1 or 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tepotinib, Bioequivalence, Pharmacokinetics