Clinical trial NCT03629223: Bioequivalence of TF3 and TF2 and Effect of Food on the PK of Tepotinib
Official title: Phase 1, Open-label, 3-Parts Study With Crossover Design in Each Part to Investigate the Bioequivalence of the Tablet Formulation of TF3 Compared to TF2 (Part A), and to Investigate the Influence of Food on the PK of Each TF2 (Part B) and TF3 (Part C) of Tepotinib in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Tepotinib
Pharmacokinetics
Bioequivalence
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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: Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib
timeFrame: 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: Part A, B and C: Maximum Observed Plasma Concentration (Cmax) of Tepotinib
timeFrame: 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 outcomes:
measure: Part A, B and C: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib
timeFrame: 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: Part A, B and C: Terminal Half-Life (t1/2) of Tepotinib
timeFrame: 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: Part A, B and C: Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f)
timeFrame: 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: Part A, B and C: Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (Vz/f)
timeFrame: 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: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Values
timeFrame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
timeFrame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: Time from date of informed consent signature up to end of study (assessed up to 7 weeks)
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: