Tepotinib Hepatic Impairment Trial

Study Overview
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Brief Summary
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The study will investigate the effect of various degrees of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of tepotinib.

Official Title
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Open-Label, Parallel-Group Phase 1 Study to Investigate the Effect of Various Degrees of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of the c-Met Kinase Inhibitor Tepotinib

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Tepotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (of nonchildbearing potential), with a body mass index of 18 to 36 kilograms per meter square (inclusive) and a body weight greater than or equal to 50 kilograms at screening, with the absence of acute hepatitis or Human Immunodeficiency Virus 1 and 2, who have given informed consent and are willing and able to comply with study procedures will be eligible for enrollment Participants with impaired hepatic function (Child-Pugh class A or Child-Pugh class B) and participants with normal hepatic function will be eligible to enroll in the study Other protocol defined inclusion criteria could apply Exclusion Criteria: Healthy participants will be excluded if they have hepatitis B or C or had a previous infection with hepatitis C treated with Sofosbuvir or other antiviral compounds, or any other clinically relevant disease, as considered by the Investigator Participants with impaired hepatic function will be excluded if they have primary biliary liver cirrhosis, nonstabilized chronic heart failure, hepatocarcinoma, hepatic encephalopathy (Grade III or IV), sepsis or gastrointestinal bleeding, or any other clinically relevant disease, as considered by the Investigator Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1, Child-Pugh Class A: Tepotinib<br> | Drug: Tepotinib<br>* Participants will receive a single oral dose of tepotinib in Part 1.<br>|
| Experimental: Part 1, Child-Pugh Class B: Tepotinib<br> | Drug: Tepotinib<br>* Participants will receive a single oral dose of tepotinib in Part 1.<br>|
| Experimental: Part 1, Healthy Participants: Tepotinib<br>Healthy participants matched to Child-Pugh Class B participants. | Drug: Tepotinib<br>* Participants will receive a single oral dose of tepotinib in Part 1.<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 (AUC 0-t) of Tepotinib |  | Pre-dose up to Day 22 | 
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib |  | Pre-dose up to Day 22 | 
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib |  | Pre-dose up to Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach the Maximum Plasma Concentration (tmax) of Tepotinib |  | Pre-dose up to Day 22 | 
| Terminal Half-Life (t1/2) of Tepotinib |  | Pre-dose up to Day 22 | 
| Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f) |  | Pre-dose up to Day 22 | 
| Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (VZ/f) |  | Pre-dose up to Day 22 | 
| Area Under the Plasma Concentration-Time Curve Extrapolated From Time t to Infinity as a Percentage of AUC 0-inf (AUC extra%) of Tepotinib |  | Pre-dose up to Day 22 | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Tepotinib Metabolites MSC2571109 and MSC2571107 |  | Pre-dose up to Day 22 | 
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib Metabolites MSC2571109 and MSC2571107 |  | Pre-dose up to Day 22 | 
| Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites MSC2571109 and MSC2571107 |  | Pre-dose up to Day 22 | 
| Time to Reach the Maximum Plasma Concentration (tmax) of Tepotinib Metabolites MSC2571109 and MSC2571107 |  | Pre-dose up to Day 22 | 
| Terminal Half-Life (t1/2) of Tepotinib Metabolites MSC2571109 and MSC2571107 |  | Pre-dose up to Day 22 | 
| Area Under the Plasma Concentration-time Curve Extrapolated From Time t to Infinity as a Percentage of AUC 0-inf (AUC extra%) of Tepotinib Metabolites MSC2571109 and MSC2571107 |  | Pre-dose up to Day 22 | 
| Tepotinib Metabolites (MSC2571109 or MSC2571107) AUC 0-inf to tepotinib AUC 0-inf ratio (MRAUC0-inf) |  | Pre-dose up to Day 22 | 
| Tepotinib Metabolites (MSC2571109 or MSC2571107) Cmax to tepotinib Cmax ratio (MRCmax) |  | Pre-dose up to Day 22 | 
| Occurrences of Treatment-emergent Adverse Events (TEAEs) |  | Day 1 up to Day 22 | 
| Number of Subjects With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings | Number of subjects with clinically significant abnormalities will be reported. | Day 1 up to Day 22 | 

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