Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK

October 8, 2025 updated by: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phase I Open-label, Single Dose Study to Investigate the Effect of Hepatic Impairment on the PK of Evobrutinib (M2951)

This study was to investigate the pharmacokinetic (PK) and safety of M2951 (Bruton's tyrosine kinase [BTK] inhibitor) in participants with different degrees of hepatic impairment compared to participants with normal hepatic function.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Kiel, Germany
        • CRS Clinical Research Services Kiel GmbH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Participants with normal hepatic function only will be overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion OR
  • Participants with moderately impaired hepatic function only will be considered to have moderately (Child-Pugh class B and confirmed liver cirrhosis) impaired hepatic function and has been clinically stable for at least 1 month prior to Screening OR
  • Participants with mildly impaired hepatic function only will be considered to have mildly (Child-Pugh class A and confirmed liver cirrhosis) impaired hepatic function and has been clinically stable for at least 1 month prior to Screening
  • Have a body weight within 50.0 and 120.0 kilogram (kg) and body mass index (BMI) within the range 19.0 and 36.0 kilogram per square meter (kg/m^2)
  • Female participants are not pregnant or breastfeeding, and at least one of the following conditions applies
  • Not a woman of childbearing potential (WOCBP)
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Clinical history of autoimmune disorder with hepatic influence (Hashimoto thyroiditis and rheumatic diseases allowed)
  • History of any malignancy
  • Diseases and surgeries of the gastrointestinal tract, which could influence the gastrointestinal anatomy and mobility. Prior history of cholecystectomy or inflammatory bowel disease, and any clinically relevant surgery within 6 months prior to Screening
  • History of chronic or recurrent acute infection or any bacterial, viral, parasitic or fungal infections within 30 days prior to Screening and at any time between Screening and admission, or hospitalization due to infection within 6 months prior to Screening
  • History of shingles within 12 months prior to Screening
  • History of drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other hypersensitivity reaction in general, which may affect the safety of the participant and/or outcome of the trial per the Investigator's discretion
  • Participants with impaired hepatic function will be excluded who had Primary and secondary biliary cirrhosis.
  • Participants with impaired hepatic function will be excluded with Clinical evidence of severe ascites.
  • Participants with impaired hepatic function will be excluded with Hepatic encephalopathy Grade greater than 1
  • Other protocol defined exclusion criteria could apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group 1: Normal Hepatic Function (Reference)
Participants with normal hepatic function received single oral dose of 30 milligrams (mg) M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast.
Drug: M2951 (BTK inhibitor)
Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.
Other Names:
  • Evobrutinib
Experimental: Group 2: Mild Hepatic Impairment
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received single oral dose of 30 mg M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. The Child-Pugh Score was a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon serum albumin, ascites, serum bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
Drug: M2951 (BTK inhibitor)
Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.
Other Names:
  • Evobrutinib
Experimental: Group 3: Moderate Hepatic Impairment
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received single oral dose of 30 mg M2951 (3 film-coated tablets of 10 mg) on Day 1 after a standard breakfast. The Child-Pugh Score was a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon serum albumin, ascites, serum bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
Drug: M2951 (BTK inhibitor)
Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.
Other Names:
  • Evobrutinib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
AUC0-inf was calculated by combining AUC0-tlast and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Cmax was obtained directly from the plasma concentration versus time curve.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: up to follow-up (Day 6)
An adverse event (AE) was defined as any unfavorable 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. TEAEs were defined as events that started or worsened that in severity after at least one dose of the study intervention has been administered. TEAEs included both serious TEAEs and non-serious TEAEs.
up to follow-up (Day 6)
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets and reticulocytes. Change from baseline in hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, and reticulocytes at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameters: basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes and reticulocytes/erythrocytes. Change From Baseline in hematology parameters: basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes and reticulocytes/erythrocytes at Day 2 and Day 6 were reported in percentage.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Change from baseline in hematology parameter: erythrocytes mean corpuscular hemoglobin at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameter: erythrocytes mean corpuscular volume. Change from baseline in hematology parameter: erythrocytes mean corpuscular volume at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameter: Erythrocytes
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameters: erythrocytes. Change from baseline in hematology parameters: erythrocytes at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameter: Hematocrit
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameter: hematocrit. Change from baseline in hematology parameter: hematocrit at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameter: Hemoglobin
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameter: hemoglobin. Change from baseline in hematology parameter: hemoglobin at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameter: Prothrombin International Normalized Ratio. International Normalized Ratio (INR) is calculated based on the prothrombin time (PT) test results. The INR is the ratio of a participant's prothrombin time to a normal (control) sample, raised to the power of the International Sensitivity Index (ISI) value for the analytical system being used. Change from baseline in hematology parameter: prothrombin international normalized ratio at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Hematology Parameter: Prothrombin Time
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the hematology parameter: prothrombin time. Prothrombin Time measures how long it takes for a clot to form in a blood sample. Change from baseline in hematology parameter: prothrombin time at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the chemistry parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Amylase, Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase (LDH) and Lipase. Change from baseline in chemistry parameters: ALT, ALP, Amylase, AST, CK, GGT, LDH and Lipase at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Chemistry Parameters: Albumin and Protein
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the chemistry parameters: Albumin and Protein. Change from baseline in chemistry parameters: albumin and protein level at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the chemistry parameters: Bilirubin, Creatinine and Urate. Change from baseline in chemistry parameters: bilirubin, creatinine and urate level at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Chemistry Parameter: C Reactive Protein
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the chemistry parameter: C Reactive Protein. Change from baseline in chemistry parameters: C Reactive Protein level at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen
Time Frame: Baseline, Day 2 and follow-up (Day 6)
Blood samples were collected in a fasted condition (after a fast of at least 8 hours) to analyze the chemistry parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen. Change from baseline in chemistry parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen level at Day 2 and Day 6 were reported.
Baseline, Day 2 and follow-up (Day 6)
Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate
Time Frame: Baseline, Day 1 and follow-up (Day 6)
12-lead ECG recordings were obtained after the participants have rested for at least 5 minutes in supine position by using an ECG machine that automatically calculates the heart rate. Change from baseline in 12-lead ECG parameter: heart rate at Day 1 and Day 6 were reported.
Baseline, Day 1 and follow-up (Day 6)
Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: PQ/PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF) and RR Duration at Day 1 and Day 6
Time Frame: Baseline, Day 1 and follow-up (Day 6)
12-lead ECG recordings were obtained after the participants have rested for at least 5 minutes in supine position by using an ECG machine that automatically measures PQ/PR, QRS, QT, and QTc intervals and RR duration. Change From Baseline in 12-ECG parameters: PQ/PR interval, QRS duration, QT interval, QTcF interval and RR duration at Day 1 and Day 6 were reported.
Baseline, Day 1 and follow-up (Day 6)
Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time Frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Change from baseline in SBP and DBP at Days 1, 2 and 6 were reported.
Baseline, Day 1, Day 2 and follow-up (Day 6)
Change From Baseline in Vital Sign Parameter: Pulse Rate
Time Frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Change from baseline in vital sign parameter: pulse rate at Days 1, 2 and 6 were reported.
Baseline, Day 1, Day 2 and follow-up (Day 6)
Change From Baseline in Vital Sign Parameter: Respiratory Rate
Time Frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Change from baseline in vital sign parameter: respiratory rate at Days 1, 2 and 6 were reported.
Baseline, Day 1, Day 2 and follow-up (Day 6)
Change From Baseline in Vital Sign Parameter: Temperature
Time Frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Temperature was measured in the semi-supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Change from baseline in vital sign parameter: temperature at Days 1, 2 and 6 were reported.
Baseline, Day 1, Day 2 and follow-up (Day 6)
Time to Reach the Maximum Plasma Concentration (Tmax) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Tmax was obtained directly from the concentration versus time curve.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Apparent Elimination Half Life (t1/2) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours (AUC0-12) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0 and 12.0 hours post-dose
AUC0-12 of M2951 was defined as the area under the plasma concentration time curve from time 0 to 12 hours post-dose.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0 and 12.0 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours (AUC0-24) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0 and 24.0 hours post-dose
AUC0-24 of M2951 was defined as the area under the plasma concentration time curve from time 0 to 24 hours post-dose.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0 and 24.0 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-tlast was calculated according to the mixed log-linear trapezoidal rule.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Apparent Total Body Clearance (CL/f) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Apparent Volume of Distribution During Terminal Phase (VZ/f) of M2951
Time Frame: Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing. Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose. AUC0-inf was calculated by combining AUC0-tlast and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 32.0 hours post-dose
Fraction of Unbound Drug (fu) of M2951
Time Frame: 1.5, 4, and 12 hours post-dose
fu is defined as the ratio of unbound drug concentration to the total drug concentration.
1.5, 4, and 12 hours post-dose
Area Under Plasma Concentration for Unbound Drug (M2951) From Time Zero to Infinity (AUC0-inf,u)
Time Frame: 1.5, 4, and 12 hours post-dose
AUC0-inf,u was calculated as fu * AUC0-inf. fu was defined as the ratio of unbound drug concentration to the total drug concentration. AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
1.5, 4, and 12 hours post-dose
Maximum Observed Plasma Concentration of Unbound M2951 (Cmax, u)
Time Frame: 1.5, 4, and 12 hours post-dose
Cmax,u was calculated as fu * Cmax. fu was defined as the ratio of unbound drug concentration to the total drug concentration. Cmax was obtained directly from the concentration versus time curve.
1.5, 4, and 12 hours post-dose
Apparent Oral Clearance (CL,u/F) of Unbound M2951
Time Frame: 1.5, 4, and 12 hours post-dose
CL,u/F was calculated as Dose divided by AUC0-inf, u. AUC0-inf,u was calculated as fu * AUC0-inf. fu was defined as the ratio of unbound drug concentration to the total drug concentration. AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
1.5, 4, and 12 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 30, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 16, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 16, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 10, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 14, 2020

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 8, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS200527_0059
  • 2020-001920-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website http://bit.ly/IPD21

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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