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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001920-32 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Experimental | 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. |
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| Group 2: Mild Hepatic Impairment | Experimental | 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. |
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| Group 3: Moderate Hepatic Impairment | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| M2951 (BTK inhibitor) | Drug | Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951 | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRS Clinical Research Services Kiel GmbH | Kiel | Germany |
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| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
| Medical Information Location Map - Med Info Contacts | View source |
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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
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A total of 32 participants were screened. Out of which, 24 participants were enrolled and treated in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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. |
| FG002 | Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The Safety analysis population (SAF) included all participants who were administered any dose of any study intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Group 2: Mild Hepatic Impairment (Child-Pugh Class A) |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951 | 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. | The Pharmacokinetic Analysis Population (PK) was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active Investigational Medicinal Product (IMP) and provide at least one measurable post-dose concentration. A measurement below lower limit of quantification (BLQ) is considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | 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 |
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up to follow-up (Day 6)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 22, 2020 | Oct 8, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 2, 2021 | Oct 8, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000632111 | evobrutinib |
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| up to follow-up (Day 6) |
| Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | 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 | 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 |
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. |
| BG002 | Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | 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. |
| OG001 | Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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. |
| OG002 | Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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. |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of M2951 | Cmax was obtained directly from the plasma concentration versus time curve. | The PK population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLOQ is considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 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 |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | up to follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | percentage of cells | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | picogram | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | femtoliters | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | 10^12 cells per liter | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameter: Hematocrit | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | liter of cells per liter of blood (L/L) | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameter: Hemoglobin | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | gram per liter (g/L) | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | ratio | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Hematology Parameter: Prothrombin Time | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | seconds | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | units per litre (U/L) | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Chemistry Parameters: Albumin and Protein | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | g/L | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | micromole per liter (mcmol/L) | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Chemistry Parameter: C Reactive Protein | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | milligram per liter (mg/L) | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | millimole per liter (mmol/L) | Baseline, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Day 1 and follow-up (Day 6) |
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| Secondary | 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 | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | milliseconds | Baseline, Day 1 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | millimeters of mercury (mmHg) | Baseline, Day 1, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Vital Sign Parameter: Pulse Rate | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Day 1, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Vital Sign Parameter: Respiratory Rate | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | breaths per minute | Baseline, Day 1, Day 2 and follow-up (Day 6) |
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| Secondary | Change From Baseline in Vital Sign Parameter: Temperature | 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. | SAF included all participants who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | degree celsius | Baseline, Day 1, Day 2 and follow-up (Day 6) |
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| Secondary | Time to Reach the Maximum Plasma Concentration (Tmax) of M2951 | Tmax was obtained directly from the concentration versus time curve. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Median | Full Range | hours | 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 |
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| Secondary | Apparent Elimination Half Life (t1/2) of M2951 | 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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Median | Full Range | hours | 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 |
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| Secondary | Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours (AUC0-12) of M2951 | AUC0-12 of M2951 was defined as the area under the plasma concentration time curve from time 0 to 12 hours post-dose. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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 |
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours (AUC0-24) of M2951 | AUC0-24 of M2951 was defined as the area under the plasma concentration time curve from time 0 to 24 hours post-dose. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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 |
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of M2951 | 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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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 |
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| Secondary | Apparent Total Body Clearance (CL/f) of M2951 | 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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | 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 |
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| Secondary | Apparent Volume of Distribution During Terminal Phase (VZ/f) of M2951 | 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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | 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 |
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| Secondary | Fraction of Unbound Drug (fu) of M2951 | fu is defined as the ratio of unbound drug concentration to the total drug concentration. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio of unbound drug | 1.5, 4, and 12 hours post-dose |
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| Secondary | Area Under Plasma Concentration for Unbound Drug (M2951) From Time Zero to Infinity (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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 1.5, 4, and 12 hours post-dose |
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| Secondary | Maximum Observed Plasma Concentration of Unbound M2951 (Cmax, u) | 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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1.5, 4, and 12 hours post-dose |
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| Secondary | Apparent Oral Clearance (CL,u/F) of Unbound M2951 | 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. | The PK Population was a subset of the SAF analysis population and consisted of all participants who received at least one dose of active IMP and provide at least one measurable post-dose concentration. A measurement BLQ was considered a valid measurement. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | 1.5, 4, and 12 hours post-dose |
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| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG002 | Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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. | 0 | 8 | 0 | 8 | 1 | 8 |
Submission of publications to Merck for review at least 60 days prior planned publication. Merck has to provide feedback within 60 days, if any confidential information other than study data is concerned. Should any patent rights be effected, Merck has right to delay publication for another 60 days for patent filing.
| Ratio of geometric least square mean |
| 1.85 |
| 2-Sided |
| 90 |
| 1.51 |
| 2.26 |
| Other |
|
| Eosinophils: Day 2 |
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| Eosinophils: follow- up (Day 6) |
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| Leukocytes: Day 2 |
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| Leukocytes: follow- up (Day 6) |
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| Lymphocytes: Day 2 |
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| Lymphocytes: follow- up (Day 6) |
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| Monocytes: Day 2 |
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| Monocytes: follow- up (Day 6) |
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| Neutrophils: Day 2 |
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| Neutrophils: follow- up (Day 6) |
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| Platelets: Day 2 |
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| Platelets: follow- up (Day 6) |
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| Reticulocytes: Day 2 |
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| Reticulocytes: follow- up (Day 6) |
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| Eosinophils/Leukocytes: Day 2 |
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| Eosinophils/Leukocytes: follow- up (Day 6) |
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| Lymphocytes/Leukocytes: Day 2 |
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| Lymphocytes/Leukocytes: follow- up (Day 6) |
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| Monocytes/Leukocytes: Day 2 |
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| Monocytes/Leukocytes: follow- up (Day 6) |
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| Neutrophils/Leukocytes: Day 2 |
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| Neutrophils/Leukocytes: follow- up (Day 6) |
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| Reticulocytes/Erythrocyte: Day 2 |
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| Reticulocytes/Erythrocyte: follow- up (Day 6) |
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| ALP: Day 2 |
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| ALP: follow- up (Day 6) |
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| Amylase: Day 2 |
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| Amylase: follow- up (Day 6) |
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| AST: Day 2 |
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| AST: follow- up (Day 6) |
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| CK: Day 2 |
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| CK: follow- up (Day 6) |
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| GGT: Day 2 |
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| GGT: follow- up (Day 6) |
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| LDH: Day 2 |
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| LDH: follow- up (Day 6) |
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| Lipase: Day 2 |
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| Lipase: follow- up (Day 6) |
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| Protein: Day 2 |
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| Protein: follow- up (Day 6) |
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| Creatinine: Day 2 |
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| Creatinine: follow- up (Day 6) |
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| Urate: Day 2 |
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| Urate: follow- up (Day 6) |
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| Chloride: Day 2 |
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| Chloride: follow- up (Day 6) |
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| Cholesterol: Day 2 |
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| Cholesterol: follow- up (Day 6) |
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| Glucose: Day 2 |
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| Glucose: follow- up (Day 6) |
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| Magnesium: Day 2 |
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| Magnesium: follow- up (Day 6) |
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| Phosphate: Day 2 |
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| Phosphate: follow- up (Day 6) |
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| Potassium: Day 2 |
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| Potassium: follow- up (Day 6) |
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| Sodium: Day 2 |
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| Sodium: follow- up (Day 6) |
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| Triglycerides: Day 2 |
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| Triglycerides: follow- up (Day 6) |
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| Urea: Day 2 |
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| Urea: follow- up (Day 6) |
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| Urea Nitrogen: Day 2 |
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| Urea Nitrogen: follow- up (Day 6) |
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| QRS Duration :Day 1 |
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| QRS Duration: follow-up (Day 6) |
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| QT Duration: Day 1 |
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| QT Duration: follow-up (Day 6) |
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| QTcF - Fridericia's Correction Formula: Day 1 |
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| QTcF - Fridericia's Correction Formula: follow-up (Day 6) |
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| RR Duration: Day 1 |
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| RR Duration: follow-up (Day 6) |
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| SBP: follow-up (Day 6) |
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| DBP: Day 1 |
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| DBP: Day 2 |
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| DBP: follow-up (Day 6) |
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| Follow-up (Day 6) |
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| Follow-up (Day 6) |
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| Follow-up (Day 6) |
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| Ratio of geometric least square mean |
| 0.51 |
| 2-Sided |
| 90 |
| 0.42 |
| 0.63 |
| Other |
| Ratio of geometric least square mean |
| 2.55 |
| 2-Sided |
| 90 |
| 1.98 |
| 3.29 |
| Other |
| Ratio of geometric least square mean |
| 2.42 |
| 2-Sided |
| 90 |
| 1.87 |
| 3.14 |
| Other |
| Ratio of geometric least square mean |
| 0.39 |
| 2-Sided |
| 90 |
| 0.30 |
| 0.50 |
| Other |