Bioequivalence of 5 Tablets of 100 mg Versus 2 Tablets of 250 mg TF3 of Tepotinib
- Registration Number
- NCT04204902
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Test Treatment then Reference Treatment Tepotinib 100 mg 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. Test Treatment then Reference Treatment Tepotinib 250 mg 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. Reference Treatment then Test Treatment Tepotinib 100 mg 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. Reference Treatment then Test Treatment Tepotinib 250 mg 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.
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib 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 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.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib 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 (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).
Maximum Observed Plasma Concentration (Cmax) of Tepotinib 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 Cmax was obtained directly from the concentration versus time curve.
- Secondary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs Baseline up to Day 59 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.
Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib 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 Tmax was obtained directly from the concentration versus time curve.
Terminal Half-Life (t1/2) of Tepotinib 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 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.
Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib 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 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.
Apparent Total Body Clearance (CL/f) of Tepotinib 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 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation Baseline up to Day 59 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.
Trial Locations
- Locations (1)
Nuvisan GmbH
🇩🇪Neu-Ulm, Germany