Phase 1
N=18
Tepotinib Hepatic Impairment Trial
Hepatic Impairment
Bottom Line
View on ClinicalTrials.gov: NCT03546608 ↗Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Aug 2024
Primary outcome: Primary: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib — 27500; 26100; 24200 Nanogram*hour per milliliter (ng*h/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Tepotinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Primary completion
- Feb 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib |
27500; 26100; 24200 | — |
| PRIMARY Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib |
27000; 25600; 23500 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Tepotinib |
406; 416; 288 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib |
11; 11.00; 16.00 | — |
| SECONDARY Apparent Terminal Half Life (t1/2) of Tepotinib |
36.8; 43.7; 46.1 | — |
| SECONDARY Apparent Total Body Clearance (CL/f) of Tepotinib |
16.4; 17.2; 18.6 | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib |
892; 1050; 1400 | — |
| SECONDARY Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib |
1.34; 5.01; 3.35; 1.06; 0.895; 3.03 | — |
| SECONDARY Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109) |
0.799; 1.44; 2.05; 1.28; 0.574; 1.41 | — |
| SECONDARY Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107) |
0.592; 3.69; 2.10; 0.925; 0.848; 5.68 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib |
532; 585; 653 | — |
| SECONDARY Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib |
7.87; 9.32; 7.80 | — |
| SECONDARY Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib |
845; 770; 689 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib Metabolites (MSC2571109 and MSC2571107) |
13300; 11000; 18100; 1120; 1120; 1050 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107) |
13400; 11100; 18500; 1130; 1140; 1080 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) |
143; 132; 165; 13.9; 14.8; 10.1 | — |
| SECONDARY Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107) |
24.00; 24.00; 54.00; 24.00; 24.00; 30.00 | — |
| SECONDARY Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107) |
46.3; 57.5; 78.8; 46.8; 40.7; 75.4 | — |
| SECONDARY Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio |
0.489; 0.424; 0.764; 0.0410; 0.0435; 0.0449 | — |
| SECONDARY Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio |
0.353; 0.318; 0.571; 0.0343; 0.0357; 0.0351 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
1; 0; 2 | — |
| SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters |
0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0; 0 | — |
Summary
The study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of tepotinib.
Eligibility Criteria
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 gave informed consent and are willing and able to comply with study procedures were eligible for enrollment
- Participants with impaired hepatic function (Child-Pugh class A or Child-Pugh class B) and participants with normal hepatic function were eligible to enroll in the study
- Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Healthy participants were 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 were 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
Data sourced from ClinicalTrials.gov (NCT03546608). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.