Tepotinib Hepatic Impairment Trial

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 5, 2019

Interventions

  • Drug: Tepotinib
    • Participants will receive a single oral dose of tepotinib in Part 1.

Arms, Groups and Cohorts

  • Experimental: Part 1, Child-Pugh Class A: Tepotinib
  • Experimental: Part 1, Child-Pugh Class B: Tepotinib
  • Experimental: Part 1, Healthy Participants: Tepotinib
    • Healthy participants matched to Child-Pugh Class B participants.

Clinical Trial Outcome Measures

Primary Measures

  • Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Tepotinib
    • Time Frame: Pre-dose up to Day 22
  • Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib
    • Time Frame: Pre-dose up to Day 22
  • Maximum Observed Plasma Concentration (Cmax) of Tepotinib
    • Time Frame: Pre-dose up to Day 22

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • EMD Serono Research & Development Institute, Inc.
  • Collaborator
    • Merck KGaA, Darmstadt, Germany
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Responsible, Study Director, EMD Serono Research & Development Institute, Inc., the biopharmaceutical division of Merck KGaA, Darmstadt, Germany

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