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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tepotinib 100 mg; Drug: Tepotinib 250 mg

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany, 89231
    • Nuvisan GmBH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bioequivalence; Tepotinib
• Additional Relevant MeSH Terms: Antineoplastic Agents; Tepotinib
• Other Study ID Numbers: MS200095_0038; 2019-003578-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No