Hepatic ImpairmentPhase 1NCT03546608
Tepotinib Hepatic Impairment Trial
A Phase 1 study testing Tepotinib in people with Hepatic Impairment, run by EMD Serono Research & Development Institute, Inc. at 2 sites in United States.
Trial summary
The study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of tepotinib. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Tepotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Jun 2018to 5 Feb 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Qps Mra, Llc
Miami, Florida, 33143
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: Open-Label, Parallel-Group Phase 1 Study to Investigate the Effect of Various Degrees of Hepatic Impairment on the PK, Safety and Tolerability of the c-Met Kinase Inhibitor Tepotinib
The study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of tepotinib.
- Conditions
- Hepatic Impairment
- Being tested
- Tepotinib
- Keywords
- Hepatic Impairment, Tepotinib, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TepotinibDrug
Participants received a single oral dose of tepotinib in Part 1.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Participants (Control) | Experimental | Participants with normal hepatic function matched to moderate hepatic impairment received single oral dose of 500 milligrams (mg) of tepotinib film-coated tablet on Day 1 after a standard breakfast. Receives: Drug: Tepotinib |
| Mild Hepatic Impairment (Child-Pugh Class A) | Experimental | Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. Receives: Drug: Tepotinib |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Experimental | Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. Receives: Drug: Tepotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib
The area under the plasma concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of Tepotinib
Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time profile.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Secondary outcomes (20)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Terminal Half Life (t1/2) of Tepotinib
Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Total Body Clearance (CL/f) of Tepotinib
Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for tepotinib.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib
Apparent volume of distribution during the terminal phase following extravascular administration for tepotinib was calculated. Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib
AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t/AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109)
AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t/AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107)
AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t/AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib
Area under the concentration-time curve for unbound drug from time zero to infinity, calculated as AUC0-inf_pred multiplied by fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib
Maximum unbound plasma drug concentration, was calculated as Cmax*fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib
Unbound apparent oral clearance, was calculated as CL/f,u = Dose divided by AUC0-inf_pred/fu. Fu is the fraction of analyte unbound. Free fraction was calculated as the ratio of free concentration divided by total concentration at a given sampling point.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
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)
AUC0-t at which the concentration was at or above lower limit of quantification (LLOQ) was calculated according to the mixed log linear trapezoidal rule. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
The area under the concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC0-inf = AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Cmax was taken directly from the observed concentration-time profile.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio
The area under the concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC0-inf = AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. Ratio of AUC0-inf of Metabolite (MSC2571109 or MSC2571107) to AUC0-inf of tepotinib was reported.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio
Cmax was taken directly from the observed concentration-time profile. Ratio of Cmax of Metabolite (MSC2571109 or MSC2571107) to Cmax of tepotinib was reported.
Measured: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs were reported.
Measured: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory assessments included hematology, biochemistry, coagulation and urinalysis. Number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator.
Measured: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings
Vital signs included body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Number of participants with clinically significant changes from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator.
Measured: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2018
- Study start13 Jun 2018
- Primary completion5 Feb 2019
- Study completion5 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono Research & Development Institute, Inc., the biopharmaceutical division of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03546608
- Sponsor's protocol ID
- MS200095_0028
- Status last verified
- Mar 2024
- First submitted
- 23 May 2018
- Last updated
- 12 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Parallel-Group Phase 1 Study to Investigate the Effect of Various Degrees of Hepatic Impairment on the PK, Safety and Tolerability of the c-Met Kinase Inhibitor Tepotinib
- ClinicalTrials.gov ID
- NCT03546608
- Acronym / sponsor ID
- MS200095_0028
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic Impairment, Tepotinib, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 5 Feb 2019 (actual)
- Study completion
- 5 Feb 2019 (actual)
- First posted
- 6 Jun 2018 (actual)
- Results
- Posted 12 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of tepotinib.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy Participants (Control) | Experimental | Drug: TepotinibParticipants with normal hepatic function matched to moderate hepatic impairment received single oral dose of 500 milligrams (mg) of tepotinib film-coated tablet on Day 1 after a standard breakfast. |
| Mild Hepatic Impairment (Child-Pugh Class A) | Experimental | Drug: TepotinibParticipants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. |
| Moderate Hepatic Impairment (Child-Pugh Class B) | Experimental | Drug: TepotinibParticipants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 500 mg tepotinib film-coated tablet on Day 1 after a standard breakfast. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TepotinibParticipants received a single oral dose of tepotinib in Part 1. | Drug | Healthy Participants (Control), Mild Hepatic Impairment (Child-Pugh Class A), Moderate Hepatic Impairment (Child-Pugh Class B) |
Primary outcome
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
The area under the plasma concentration time curve (AUC) from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at the last sampling time (tlast), as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Maximum Observed Plasma Concentration (Cmax) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time profile.
20 secondary outcomes
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Terminal Half Life (t1/2) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Total Body Clearance (CL/f) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571109)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity as a Percentage of AUC0-Inf (AUCextra) of Tepotinib Metabolite (MSC2571107)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Area Under the Plasma Concentration Time Curve for Unbound Drug From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf, u) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Total Body Clearance of Unbound Drug Following Extravascular Administration (CL/f,u) of Tepotinib
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
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)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Time to Reach Maximum Observation Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Apparent Terminal Half Life (t1/2) of Tepotinib Metabolites (MSC2571109 and MSC2571107)
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Metabolite (MSC2571109 or MSC2571107) Area Under Curve From Time Zero Extrapolated To Infinity (AUC0-inf) to Tepotinib (AUC0-inf) Ratio
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Metabolite (MSC2571109 or MSC2571107) Maximum Observed Plasma Concentration Observed (Cmax) to Tepotinib Cmax Ratio
Time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Time frame: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and 12-lead Electrocardiogram (ECG) Findings
Time frame: For Healthy Participants: Day 1 up to Day 15; For Hepatic Impaired Participants: Day 1 up to Day 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- US Medical Information website, Medical ResourcesLink provided by the sponsor.
- Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono Research & Development Institute, Inc., the biopharmaceutical division of Merck KGaA, Darmstadt, Germany
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tepotinib in people with Hepatic Impairment, run by EMD Serono Research & Development Institute, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity ( AUC0-inf ) of Tepotinib (time frame: Pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336 and 504 hours (for hepatic impaired participants only) post-dose on Day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2024.