Tepotinib Hepatic Impairment Trial

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03546608

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Locations

Arms

7.8

Actual Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatic Impairment	Drug: Tepotinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Jun 13, 2018

Actual Primary Completion Date :

Feb 5, 2019

Actual Study Completion Date :

Feb 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1, Child-Pugh Class A: Tepotinib	Drug: Tepotinib Participants will receive a single oral dose of tepotinib in Part 1.
Experimental: Part 1, Child-Pugh Class B: Tepotinib	Drug: Tepotinib Participants will receive a single oral dose of tepotinib in Part 1.
Experimental: Part 1, Healthy Participants: Tepotinib Healthy participants matched to Child-Pugh Class B participants.	Drug: Tepotinib Participants will receive a single oral dose of tepotinib in Part 1.

Arm

Intervention/Treatment

Experimental: Part 1, Child-Pugh Class A: Tepotinib

Drug: Tepotinib

Participants will receive a single oral dose of tepotinib in Part 1.

Experimental: Part 1, Child-Pugh Class B: Tepotinib

Drug: Tepotinib

Participants will receive a single oral dose of tepotinib in Part 1.

Experimental: Part 1, Healthy Participants: Tepotinib

Healthy participants matched to Child-Pugh Class B participants.

Drug: Tepotinib

Participants will receive a single oral dose of tepotinib in Part 1.

Outcome Measures

Primary Outcome Measures

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

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 [Day 1 up to Day 22]
Number of subjects with clinically significant abnormalities will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Qps Mra, Llc	Miami	Florida	United States	33143
2	Orlando Clinical Research Center	Orlando	Florida	United States	32809

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany

Investigators

Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc., the biopharmaceutical division of Merck KGaA, Darmstadt, Germany