Hepatic Impairment
Conditions
Keywords
Hepatic Impairment, Pharmacokinetics
Brief summary
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.
Interventions
DRUGM2951 (BTK inhibitor)
Participants received a single oral dose of M2951 (BTK inhibitor) on Day 1.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951 | 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. |
| Maximum Observed Plasma Concentration (Cmax) of M2951 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | 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. |
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | 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. |
| Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | 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. |
| Change From Baseline in Hematology Parameter: Erythrocytes | 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. |
| Change From Baseline in Hematology Parameter: Hematocrit | 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. |
| Change From Baseline in Hematology Parameter: Hemoglobin | 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. |
| Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | 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. |
| Change From Baseline in Hematology Parameter: Prothrombin Time | 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. |
| Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | 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. |
| Change From Baseline in Chemistry Parameters: Albumin and Protein | 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. |
| Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | 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. |
| Change From Baseline in Chemistry Parameter: C Reactive Protein | 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. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of M2951 | 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. |
| Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | 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. |
| Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. |
| Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | 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. |
| Change From Baseline in Vital Sign Parameter: Pulse Rate | 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. |
| Change From Baseline in Vital Sign Parameter: Respiratory Rate | 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. |
| Change From Baseline in Vital Sign Parameter: Temperature | 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. |
| Time to Reach the Maximum Plasma Concentration (Tmax) of M2951 | 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. |
| Apparent Elimination Half Life (t1/2) of M2951 | 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. |
| Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours (AUC0-12) of M2951 | 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. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours (AUC0-24) of M2951 | 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. |
| Apparent Total Body Clearance (CL/f) of M2951 | 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. |
| Apparent Volume of Distribution During Terminal Phase (VZ/f) of M2951 | 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. |
| Fraction of Unbound Drug (fu) of M2951 | 1.5, 4, and 12 hours post-dose | fu is defined as the ratio of unbound drug concentration to the total drug concentration. |
| Area Under Plasma Concentration for Unbound Drug (M2951) From Time Zero to Infinity (AUC0-inf,u) | 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. |
| Maximum Observed Plasma Concentration of Unbound M2951 (Cmax, u) | 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. |
| Apparent Oral Clearance (CL,u/F) of Unbound M2951 | 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. |
| 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 | 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. |
| Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | 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. |
Countries
Germany
Participant flow
Pre-assignment details
A total of 32 participants were screened. Out of which, 24 participants were enrolled and treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 8 |
| 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. | 8 |
| 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. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Total | Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Group 1: Normal Hepatic Function (Reference) |
|---|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 11.3 | 60.8 years STANDARD_DEVIATION 9.6 | 58.9 years STANDARD_DEVIATION 10.4 | 65.3 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 22 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 24 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951 | 186 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.6 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951 | 232 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 60.6 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M2951 | 362 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.8 |
Comparison: Mild Hepatic Impairment vs Normal Hepatic Function90% CI: [0.86, 1.82]
Comparison: Moderate hepatic impairment vs Normal hepatic impairment90% CI: [1.6, 2.38]
Primary
Maximum Observed Plasma Concentration (Cmax) of M2951
Cmax was obtained directly from the plasma concentration versus time curve.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Maximum Observed Plasma Concentration (Cmax) of M2951 | 63.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 14.2 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Maximum Observed Plasma Concentration (Cmax) of M2951 | 79.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 86.2 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Maximum Observed Plasma Concentration (Cmax) of M2951 | 118 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29.9 |
Comparison: Mild Hepatic Impairment vs Normal Hepatic Function90% CI: [0.77, 1.99]
Comparison: Moderate Hepatic Impairment vs Normal Hepatic Function90% CI: [1.51, 2.26]
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.
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Apparent Elimination Half Life (t1/2) of M2951 | 1.54 hours |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Elimination Half Life (t1/2) of M2951 | 2.55 hours |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Elimination Half Life (t1/2) of M2951 | 2.65 hours |
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.
Time frame: 1.5, 4, and 12 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Apparent Oral Clearance (CL,u/F) of Unbound M2951 | 3230 L/h | Geometric Coefficient of Variation 30.3 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Oral Clearance (CL,u/F) of Unbound M2951 | 2240 L/h | Geometric Coefficient of Variation 71.7 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Oral Clearance (CL,u/F) of Unbound M2951 | 1270 L/h | Geometric Coefficient of Variation 28.5 |
Comparison: Mild Hepatic Impairment vs Normal Hepatic Function90% CI: [0.45, 1.08]
Comparison: Moderate Hepatic Impairment vs Normal Hepatic Function90% CI: [0.3, 0.5]
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Apparent Total Body Clearance (CL/f) of M2951 | 162 liter per hour (L/h) | Geometric Coefficient of Variation 23.6 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Total Body Clearance (CL/f) of M2951 | 129 liter per hour (L/h) | Geometric Coefficient of Variation 60.6 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Total Body Clearance (CL/f) of M2951 | 82.9 liter per hour (L/h) | Geometric Coefficient of Variation 21.8 |
Comparison: Mild Hepatic Impairment vs Normal Hepatic Function90% CI: [0.55, 1.17]
Comparison: Moderate Hepatic Impairment vs Normal Hepatic Function90% CI: [0.42, 0.63]
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Apparent Volume of Distribution During Terminal Phase (VZ/f) of M2951 | 337 liters | Geometric Coefficient of Variation 15.2 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Apparent Volume of Distribution During Terminal Phase (VZ/f) of M2951 | 498 liters | Geometric Coefficient of Variation 53.4 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Apparent Volume of Distribution During Terminal Phase (VZ/f) of M2951 | 301 liters | Geometric Coefficient of Variation 27 |
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.
Time frame: 1.5, 4, and 12 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Area Under Plasma Concentration for Unbound Drug (M2951) From Time Zero to Infinity (AUC0-inf,u) | 9.28 h*ng/mL | Geometric Coefficient of Variation 30.3 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Area Under Plasma Concentration for Unbound Drug (M2951) From Time Zero to Infinity (AUC0-inf,u) | 13.4 h*ng/mL | Geometric Coefficient of Variation 71.7 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under Plasma Concentration for Unbound Drug (M2951) From Time Zero to Infinity (AUC0-inf,u) | 23.7 h*ng/mL | Geometric Coefficient of Variation 28.5 |
Comparison: Mild Hepatic Impairment vs Normal Hepatic Function90% CI: [0.93, 2.25]
Comparison: Moderate Hepatic Impairment vs Normal Hepatic Function90% CI: [1.98, 3.29]
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of M2951 | 184 h*ng/mL | Geometric Coefficient of Variation 23.9 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of M2951 | 228 h*ng/mL | Geometric Coefficient of Variation 60.9 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of M2951 | 357 h*ng/mL | Geometric Coefficient of Variation 22.3 |
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours (AUC0-12) of M2951 | 184 h*ng/mL | Geometric Coefficient of Variation 23.6 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours (AUC0-12) of M2951 | 224 h*ng/mL | Geometric Coefficient of Variation 59.7 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours (AUC0-12) of M2951 | 351 h*ng/mL | Geometric Coefficient of Variation 21.7 |
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours (AUC0-24) of M2951 | 185 h*ng/mL | Geometric Coefficient of Variation 23.8 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours (AUC0-24) of M2951 | 231 h*ng/mL | Geometric Coefficient of Variation 60.1 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours (AUC0-24) of M2951 | 360 h*ng/mL | Geometric Coefficient of Variation 22 |
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.
Time frame: Baseline, Day 1 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | Day 1 | 0.3 beats per minute | Standard Deviation 5.18 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | Follow- up (Day 6) | 11.8 beats per minute | Standard Deviation 11.02 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | Day 1 | -0.9 beats per minute | Standard Deviation 5.33 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | Follow- up (Day 6) | 7.4 beats per minute | Standard Deviation 11.34 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | Day 1 | 0.9 beats per minute | Standard Deviation 2.7 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameter: Heart Rate | Follow- up (Day 6) | 5.8 beats per minute | Standard Deviation 6.34 |
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.
Time frame: Baseline, Day 1 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | 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 | PQ/PR Duration: Day 1 | -0.3 milliseconds | Standard Deviation 4.71 |
| Group 1: Normal Hepatic Function (Reference) | 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 | PQ/PR Duration: follow-up (Day 6) | -12.5 milliseconds | Standard Deviation 11.05 |
| Group 1: Normal Hepatic Function (Reference) | 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 | QRS Duration :Day 1 | 0.0 milliseconds | Standard Deviation 3.21 |
| Group 1: Normal Hepatic Function (Reference) | 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 | QRS Duration: follow-up (Day 6) | -1.3 milliseconds | Standard Deviation 3.01 |
| Group 1: Normal Hepatic Function (Reference) | 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 | QT Duration: Day 1 | -7.3 milliseconds | Standard Deviation 17.33 |
| Group 1: Normal Hepatic Function (Reference) | 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 | QT Duration: follow-up (Day 6) | -24.3 milliseconds | Standard Deviation 18.77 |
| Group 1: Normal Hepatic Function (Reference) | 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 | QTcF - Fridericia's Correction Formula: Day 1 | -6.8 milliseconds | Standard Deviation 20.11 |
| Group 1: Normal Hepatic Function (Reference) | 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 | QTcF - Fridericia's Correction Formula: follow-up (Day 6) | -2.4 milliseconds | Standard Deviation 9.98 |
| Group 1: Normal Hepatic Function (Reference) | 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 | RR Duration: Day 1 | -6.1 milliseconds | Standard Deviation 79.08 |
| Group 1: Normal Hepatic Function (Reference) | 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 | RR Duration: follow-up (Day 6) | -148.1 milliseconds | Standard Deviation 126.54 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | RR Duration: Day 1 | 9.0 milliseconds | Standard Deviation 92.82 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | PQ/PR Duration: Day 1 | 0.3 milliseconds | Standard Deviation 4.46 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | QT Duration: follow-up (Day 6) | -5.5 milliseconds | Standard Deviation 22.72 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | QT Duration: Day 1 | -0.3 milliseconds | Standard Deviation 11.97 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | PQ/PR Duration: follow-up (Day 6) | -4.5 milliseconds | Standard Deviation 9.78 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | RR Duration: follow-up (Day 6) | -87.4 milliseconds | Standard Deviation 130.73 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | QTcF - Fridericia's Correction Formula: follow-up (Day 6) | 9.1 milliseconds | Standard Deviation 11.49 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | QRS Duration :Day 1 | 2.3 milliseconds | Standard Deviation 5.06 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | QTcF - Fridericia's Correction Formula: Day 1 | -1.8 milliseconds | Standard Deviation 4.89 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | 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 | QRS Duration: follow-up (Day 6) | 3.0 milliseconds | Standard Deviation 8.28 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | QTcF - Fridericia's Correction Formula: follow-up (Day 6) | 2.9 milliseconds | Standard Deviation 15.61 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | QRS Duration: follow-up (Day 6) | -2.0 milliseconds | Standard Deviation 7.63 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | QT Duration: Day 1 | -0.5 milliseconds | Standard Deviation 12.99 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | QT Duration: follow-up (Day 6) | -7.0 milliseconds | Standard Deviation 20.45 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | RR Duration: Day 1 | -11.0 milliseconds | Standard Deviation 37.85 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | QTcF - Fridericia's Correction Formula: Day 1 | 1.5 milliseconds | Standard Deviation 11.76 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | PQ/PR Duration: Day 1 | -2.0 milliseconds | Standard Deviation 17.47 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | RR Duration: follow-up (Day 6) | -67.4 milliseconds | Standard Deviation 91.17 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | PQ/PR Duration: follow-up (Day 6) | -10.0 milliseconds | Standard Deviation 13.52 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | 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 | QRS Duration :Day 1 | 6.5 milliseconds | Standard Deviation 9.06 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameter: C Reactive Protein | Day 2 | -0.04 milligram per liter (mg/L) | Standard Deviation 0.46 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameter: C Reactive Protein | Follow- up (Day 6) | -0.05 milligram per liter (mg/L) | Standard Deviation 0.404 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameter: C Reactive Protein | Day 2 | -0.22 milligram per liter (mg/L) | Standard Deviation 0.669 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameter: C Reactive Protein | Follow- up (Day 6) | 0.26 milligram per liter (mg/L) | Standard Deviation 0.798 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameter: C Reactive Protein | Day 2 | 0.40 milligram per liter (mg/L) | Standard Deviation 1.593 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameter: C Reactive Protein | Follow- up (Day 6) | 1.25 milligram per liter (mg/L) | Standard Deviation 2.33 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Amylase: Day 2 | 1.8 units per litre (U/L) | Standard Deviation 15.71 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALT: follow- up (Day 6) | 0.8 units per litre (U/L) | Standard Deviation 2.12 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALP: Day 2 | -3.3 units per litre (U/L) | Standard Deviation 5.47 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALP: follow- up (Day 6) | 0.4 units per litre (U/L) | Standard Deviation 5.66 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALT: Day 2 | 0.9 units per litre (U/L) | Standard Deviation 2.23 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Amylase: follow- up (Day 6) | -4.1 units per litre (U/L) | Standard Deviation 6.47 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | AST: Day 2 | -0.5 units per litre (U/L) | Standard Deviation 2.88 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | AST: follow- up (Day 6) | 0.6 units per litre (U/L) | Standard Deviation 1.92 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | CK: Day 2 | -41.9 units per litre (U/L) | Standard Deviation 40.65 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | CK: follow- up (Day 6) | -20.9 units per litre (U/L) | Standard Deviation 44.97 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | GGT: Day 2 | -0.8 units per litre (U/L) | Standard Deviation 1.39 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | GGT: follow- up (Day 6) | -1.0 units per litre (U/L) | Standard Deviation 1.85 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | LDH: Day 2 | -17.6 units per litre (U/L) | Standard Deviation 17.44 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | LDH: follow- up (Day 6) | -13.9 units per litre (U/L) | Standard Deviation 10.44 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Lipase: Day 2 | 18.4 units per litre (U/L) | Standard Deviation 50.86 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Lipase: follow- up (Day 6) | -2.4 units per litre (U/L) | Standard Deviation 7.05 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Amylase: follow- up (Day 6) | -2.6 units per litre (U/L) | Standard Deviation 3.46 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | AST: Day 2 | -24.1 units per litre (U/L) | Standard Deviation 51.88 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | AST: follow- up (Day 6) | -15.5 units per litre (U/L) | Standard Deviation 51.39 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | LDH: follow- up (Day 6) | -20.9 units per litre (U/L) | Standard Deviation 23.73 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | CK: Day 2 | -68.0 units per litre (U/L) | Standard Deviation 27.44 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | CK: follow- up (Day 6) | -15.4 units per litre (U/L) | Standard Deviation 26.42 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Lipase: follow- up (Day 6) | -1.5 units per litre (U/L) | Standard Deviation 5.35 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | GGT: Day 2 | -22.4 units per litre (U/L) | Standard Deviation 34.98 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALT: Day 2 | -9.4 units per litre (U/L) | Standard Deviation 17 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Lipase: Day 2 | -4.8 units per litre (U/L) | Standard Deviation 3.62 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALT: follow- up (Day 6) | -7.0 units per litre (U/L) | Standard Deviation 20.5 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | GGT: follow- up (Day 6) | -24.8 units per litre (U/L) | Standard Deviation 43.48 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALP: Day 2 | -14.6 units per litre (U/L) | Standard Deviation 16.04 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALP: follow- up (Day 6) | -9.5 units per litre (U/L) | Standard Deviation 14.06 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Amylase: Day 2 | -11.0 units per litre (U/L) | Standard Deviation 8.32 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | LDH: Day 2 | -42.5 units per litre (U/L) | Standard Deviation 35.62 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | GGT: Day 2 | 6.5 units per litre (U/L) | Standard Deviation 52.11 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Amylase: follow- up (Day 6) | 14.1 units per litre (U/L) | Standard Deviation 21.56 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | LDH: Day 2 | -11.3 units per litre (U/L) | Standard Deviation 33.72 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALP: Day 2 | -16.1 units per litre (U/L) | Standard Deviation 13.17 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | AST: Day 2 | 2.1 units per litre (U/L) | Standard Deviation 7.38 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Lipase: follow- up (Day 6) | 10.4 units per litre (U/L) | Standard Deviation 28.61 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALT: Day 2 | -2.0 units per litre (U/L) | Standard Deviation 3.82 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | AST: follow- up (Day 6) | 0.8 units per litre (U/L) | Standard Deviation 5.01 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | GGT: follow- up (Day 6) | -27.6 units per litre (U/L) | Standard Deviation 43 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Amylase: Day 2 | 34.1 units per litre (U/L) | Standard Deviation 107.34 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | CK: Day 2 | -36.4 units per litre (U/L) | Standard Deviation 23.08 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | LDH: follow- up (Day 6) | -10.8 units per litre (U/L) | Standard Deviation 12.71 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALT: follow- up (Day 6) | -0.4 units per litre (U/L) | Standard Deviation 2.13 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | CK: follow- up (Day 6) | -9.5 units per litre (U/L) | Standard Deviation 43.36 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | ALP: follow- up (Day 6) | -9.5 units per litre (U/L) | Standard Deviation 19.27 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Lipase | Lipase: Day 2 | -16.8 units per litre (U/L) | Standard Deviation 63.92 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Albumin: Day 2 | -1.1 g/L | Standard Deviation 2.64 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Albumin: follow- up (Day 6) | -0.6 g/L | Standard Deviation 2 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Protein: Day 2 | -1.3 g/L | Standard Deviation 3.11 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Protein: follow- up (Day 6) | -1.0 g/L | Standard Deviation 2.88 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Protein: follow- up (Day 6) | -2.8 g/L | Standard Deviation 4.92 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Albumin: Day 2 | -4.0 g/L | Standard Deviation 3.74 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Protein: Day 2 | -6.0 g/L | Standard Deviation 5.98 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Albumin: follow- up (Day 6) | -1.5 g/L | Standard Deviation 2.73 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Protein: follow- up (Day 6) | -1.5 g/L | Standard Deviation 1.93 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Albumin: follow- up (Day 6) | -0.8 g/L | Standard Deviation 0.89 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Protein: Day 2 | -3.3 g/L | Standard Deviation 4.86 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Albumin and Protein | Albumin: Day 2 | -2.3 g/L | Standard Deviation 3.11 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Bilirubin: Day 2 | -0.42760 micromole per liter (mcmol/L) | Standard Deviation 1.516108 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Bilirubin: follow- up (Day 6) | 0.21380 micromole per liter (mcmol/L) | Standard Deviation 2.131883 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Creatinine: Day 2 | -7.0720 micromole per liter (mcmol/L) | Standard Deviation 5.21913 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Creatinine: follow- up (Day 6) | -0.0000 micromole per liter (mcmol/L) | Standard Deviation 4.84187 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Urate: Day 2 | -25.2790 micromole per liter (mcmol/L) | Standard Deviation 28.03413 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Urate: follow- up (Day 6) | 5.9480 micromole per liter (mcmol/L) | Standard Deviation 38.80879 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Urate: follow- up (Day 6) | -11.8960 micromole per liter (mcmol/L) | Standard Deviation 25.82908 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Bilirubin: Day 2 | 3.41455 micromole per liter (mcmol/L) | Standard Deviation 7.539097 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Creatinine: follow- up (Day 6) | 1.7680 micromole per liter (mcmol/L) | Standard Deviation 4.7722 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Urate: Day 2 | -24.5355 micromole per liter (mcmol/L) | Standard Deviation 35.891 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Bilirubin: follow- up (Day 6) | -0.21380 micromole per liter (mcmol/L) | Standard Deviation 5.593931 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Creatinine: Day 2 | -3.0940 micromole per liter (mcmol/L) | Standard Deviation 5.8828 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Bilirubin: follow- up (Day 6) | -2.77940 micromole per liter (mcmol/L) | Standard Deviation 6.060122 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Creatinine: Day 2 | -5.3040 micromole per liter (mcmol/L) | Standard Deviation 5.78714 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Urate: follow- up (Day 6) | 8.9220 micromole per liter (mcmol/L) | Standard Deviation 18.80923 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Creatinine: follow- up (Day 6) | -0.4420 micromole per liter (mcmol/L) | Standard Deviation 2.87421 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Bilirubin: Day 2 | 3.20700 micromole per liter (mcmol/L) | Standard Deviation 7.99313 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate | Urate: Day 2 | -15.6135 micromole per liter (mcmol/L) | Standard Deviation 28.06792 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea: follow- up (Day 6) | -0.213 millimole per liter (mmol/L) | Standard Deviation 1.0149 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Sodium: follow- up (Day 6) | -0.6 millimole per liter (mmol/L) | Standard Deviation 1.77 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Magnesium: Day 2 | -0.009 millimole per liter (mmol/L) | Standard Deviation 0.0285 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Chloride: follow- up (Day 6) | -1.6 millimole per liter (mmol/L) | Standard Deviation 2.07 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Sodium: Day 2 | 0.0 millimole per liter (mmol/L) | Standard Deviation 1.6 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Magnesium: follow- up (Day 6) | -0.014 millimole per liter (mmol/L) | Standard Deviation 0.0297 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea Nitrogen: follow- up (Day 6) | -0.2231 millimole per liter (mmol/L) | Standard Deviation 0.99041 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Potassium: follow- up (Day 6) | -0.01 millimole per liter (mmol/L) | Standard Deviation 0.181 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Phosphate: Day 2 | 0.003 millimole per liter (mmol/L) | Standard Deviation 0.0509 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea: Day 2 | -0.021 millimole per liter (mmol/L) | Standard Deviation 0.9152 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Potassium: Day 2 | -0.11 millimole per liter (mmol/L) | Standard Deviation 0.356 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Phosphate: follow- up (Day 6) | -0.005 millimole per liter (mmol/L) | Standard Deviation 0.0682 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Cholesterol: Day 2 | 0.03885 millimole per liter (mmol/L) | Standard Deviation 0.287412 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea Nitrogen: Day 2 | 0.0000 millimole per liter (mmol/L) | Standard Deviation 0.89505 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Triglycerides: follow- up (Day 6) | -0.23165 millimole per liter (mmol/L) | Standard Deviation 0.875919 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Cholesterol: follow- up (Day 6) | -0.27519 millimole per liter (mmol/L) | Standard Deviation 0.47756 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Chloride: Day 2 | 1.0 millimole per liter (mmol/L) | Standard Deviation 1.07 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Calcium: Day 2 | -0.030 millimole per liter (mmol/L) | Standard Deviation 0.0481 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Glucose: Day 2 | 0.09019 millimole per liter (mmol/L) | Standard Deviation 0.622942 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Calcium: follow- up (Day 6) | -0.039 millimole per liter (mmol/L) | Standard Deviation 0.0506 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Triglycerides: Day 2 | -0.15538 millimole per liter (mmol/L) | Standard Deviation 0.940507 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Glucose: follow- up (Day 6) | 0.17344 millimole per liter (mmol/L) | Standard Deviation 0.379258 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Triglycerides: Day 2 | 0.06356 millimole per liter (mmol/L) | Standard Deviation 0.222415 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Calcium: Day 2 | -0.020 millimole per liter (mmol/L) | Standard Deviation 0.0878 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Calcium: follow- up (Day 6) | -0.033 millimole per liter (mmol/L) | Standard Deviation 0.1074 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Chloride: Day 2 | 0.5 millimole per liter (mmol/L) | Standard Deviation 2.27 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Chloride: follow- up (Day 6) | -0.4 millimole per liter (mmol/L) | Standard Deviation 1.6 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Cholesterol: Day 2 | -0.26871 millimole per liter (mmol/L) | Standard Deviation 0.5392 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Cholesterol: follow- up (Day 6) | -0.38203 millimole per liter (mmol/L) | Standard Deviation 0.701523 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Glucose: Day 2 | 0.05550 millimole per liter (mmol/L) | Standard Deviation 1.760321 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Glucose: follow- up (Day 6) | -0.32606 millimole per liter (mmol/L) | Standard Deviation 0.340109 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Magnesium: Day 2 | -0.052 millimole per liter (mmol/L) | Standard Deviation 0.0742 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Magnesium: follow- up (Day 6) | 0.005 millimole per liter (mmol/L) | Standard Deviation 0.0457 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Phosphate: Day 2 | 0.080 millimole per liter (mmol/L) | Standard Deviation 0.0953 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Phosphate: follow- up (Day 6) | -0.064 millimole per liter (mmol/L) | Standard Deviation 0.1421 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Potassium: Day 2 | -0.12 millimole per liter (mmol/L) | Standard Deviation 0.266 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Potassium: follow- up (Day 6) | 0.16 millimole per liter (mmol/L) | Standard Deviation 0.396 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Sodium: Day 2 | -2.8 millimole per liter (mmol/L) | Standard Deviation 1.39 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Sodium: follow- up (Day 6) | -0.9 millimole per liter (mmol/L) | Standard Deviation 1.25 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Triglycerides: follow- up (Day 6) | -0.02260 millimole per liter (mmol/L) | Standard Deviation 0.32611 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea: Day 2 | 0.531 millimole per liter (mmol/L) | Standard Deviation 0.7122 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea: follow- up (Day 6) | 0.149 millimole per liter (mmol/L) | Standard Deviation 0.5849 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea Nitrogen: Day 2 | 0.5801 millimole per liter (mmol/L) | Standard Deviation 0.7124 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea Nitrogen: follow- up (Day 6) | 0.1785 millimole per liter (mmol/L) | Standard Deviation 0.57247 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Sodium: Day 2 | -0.1 millimole per liter (mmol/L) | Standard Deviation 2.36 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Glucose: follow- up (Day 6) | -1.87313 millimole per liter (mmol/L) | Standard Deviation 3.54949 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Calcium: follow- up (Day 6) | -0.090 millimole per liter (mmol/L) | Standard Deviation 0.1158 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Sodium: follow- up (Day 6) | 1.8 millimole per liter (mmol/L) | Standard Deviation 2.76 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Glucose: Day 2 | -1.94944 millimole per liter (mmol/L) | Standard Deviation 2.490078 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Cholesterol: follow- up (Day 6) | -0.21691 millimole per liter (mmol/L) | Standard Deviation 0.274776 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Triglycerides: Day 2 | -0.44776 millimole per liter (mmol/L) | Standard Deviation 1.268752 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Cholesterol: Day 2 | -0.18778 millimole per liter (mmol/L) | Standard Deviation 0.233203 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea Nitrogen: follow- up (Day 6) | 0.3570 millimole per liter (mmol/L) | Standard Deviation 0.26987 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Triglycerides: follow- up (Day 6) | -0.40539 millimole per liter (mmol/L) | Standard Deviation 0.781335 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Chloride: follow- up (Day 6) | 1.6 millimole per liter (mmol/L) | Standard Deviation 2.62 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea Nitrogen: Day 2 | 0.7586 millimole per liter (mmol/L) | Standard Deviation 0.77366 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea: Day 2 | 0.765 millimole per liter (mmol/L) | Standard Deviation 0.8025 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Phosphate: follow- up (Day 6) | -0.106 millimole per liter (mmol/L) | Standard Deviation 0.1897 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Phosphate: Day 2 | 0.105 millimole per liter (mmol/L) | Standard Deviation 0.1872 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Chloride: Day 2 | 2.4 millimole per liter (mmol/L) | Standard Deviation 0.92 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Potassium: Day 2 | -0.34 millimole per liter (mmol/L) | Standard Deviation 0.487 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Magnesium: follow- up (Day 6) | -0.006 millimole per liter (mmol/L) | Standard Deviation 0.0758 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Calcium: Day 2 | -0.036 millimole per liter (mmol/L) | Standard Deviation 0.054 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Potassium: follow- up (Day 6) | -0.38 millimole per liter (mmol/L) | Standard Deviation 0.727 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Magnesium: Day 2 | -0.001 millimole per liter (mmol/L) | Standard Deviation 0.0732 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, Urea and Urea Nitrogen | Urea: follow- up (Day 6) | 0.340 millimole per liter (mmol/L) | Standard Deviation 0.257 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Erythrocytes | Day 2 | 0.017 10^12 cells per liter | Standard Deviation 0.1945 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Erythrocytes | Follow- up (Day 6) | -0.083 10^12 cells per liter | Standard Deviation 0.1348 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Erythrocytes | Day 2 | -0.096 10^12 cells per liter | Standard Deviation 0.2894 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Erythrocytes | Follow- up (Day 6) | -0.163 10^12 cells per liter | Standard Deviation 0.1992 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Erythrocytes | Day 2 | -0.113 10^12 cells per liter | Standard Deviation 0.2858 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Erythrocytes | Follow- up (Day 6) | -0.179 10^12 cells per liter | Standard Deviation 0.1787 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Follow- up (Day 6) | -0.09 picogram | Standard Deviation 0.348 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Day 2 | -0.04 picogram | Standard Deviation 0.307 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Follow- up (Day 6) | -0.02 picogram | Standard Deviation 0.225 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Day 2 | -0.25 picogram | Standard Deviation 0.389 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Day 2 | -0.07 picogram | Standard Deviation 0.373 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin | Follow- up (Day 6) | 0.06 picogram | Standard Deviation 0.487 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Hematocrit | Day 2 | 0.0022 liter of cells per liter of blood (L/L) | Standard Deviation 0.01795 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Hematocrit | Follow- up (Day 6) | -0.0042 liter of cells per liter of blood (L/L) | Standard Deviation 0.01059 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Hematocrit | Day 2 | -0.0096 liter of cells per liter of blood (L/L) | Standard Deviation 0.0265 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Hematocrit | Follow- up (Day 6) | -0.0131 liter of cells per liter of blood (L/L) | Standard Deviation 0.0184 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Hematocrit | Day 2 | -0.0112 liter of cells per liter of blood (L/L) | Standard Deviation 0.03179 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Hematocrit | Follow- up (Day 6) | -0.0174 liter of cells per liter of blood (L/L) | Standard Deviation 0.01683 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Hemoglobin | Day 2 | 0.4 gram per liter (g/L) | Standard Deviation 5.55 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Hemoglobin | Follow- up (Day 6) | -2.9 gram per liter (g/L) | Standard Deviation 3.94 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Hemoglobin | Day 2 | -4.5 gram per liter (g/L) | Standard Deviation 10.43 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Hemoglobin | Follow- up (Day 6) | -5.6 gram per liter (g/L) | Standard Deviation 6.82 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Hemoglobin | Day 2 | -3.6 gram per liter (g/L) | Standard Deviation 9.23 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Hemoglobin | Follow- up (Day 6) | -5.4 gram per liter (g/L) | Standard Deviation 4.44 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Day 2 | -0.006 ratio | Standard Deviation 0.016 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Follow- up (Day 6) | 0.021 ratio | Standard Deviation 0.0295 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Day 2 | 0.006 ratio | Standard Deviation 0.0262 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Follow- up (Day 6) | -0.006 ratio | Standard Deviation 0.058 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Day 2 | 0.006 ratio | Standard Deviation 0.0421 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Follow- up (Day 6) | -0.029 ratio | Standard Deviation 0.0391 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Prothrombin Time | Day 2 | -0.12 seconds | Standard Deviation 0.183 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameter: Prothrombin Time | Follow- up (Day 6) | 0.12 seconds | Standard Deviation 0.337 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Prothrombin Time | Day 2 | 0.04 seconds | Standard Deviation 0.245 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameter: Prothrombin Time | Follow- up (Day 6) | -0.06 seconds | Standard Deviation 0.51 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Prothrombin Time | Day 2 | 0.14 seconds | Standard Deviation 0.396 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameter: Prothrombin Time | Follow- up (Day 6) | -0.19 seconds | Standard Deviation 0.336 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Leukocytes: Day 2 | 0.54 10^9 cells per liter | Standard Deviation 0.597 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Basophils: follow- up (Day 6) | -0.003 10^9 cells per liter | Standard Deviation 0.0128 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Eosinophils: Day 2 | -0.007 10^9 cells per liter | Standard Deviation 0.0984 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Eosinophils: follow- up (Day 6) | 0.000 10^9 cells per liter | Standard Deviation 0.0626 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Basophils: Day 2 | -0.006 10^9 cells per liter | Standard Deviation 0.016 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Leukocytes: follow- up (Day 6) | 0.11 10^9 cells per liter | Standard Deviation 0.751 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Lymphocytes: Day 2 | 0.233 10^9 cells per liter | Standard Deviation 0.3186 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Lymphocytes: follow- up (Day 6) | 0.146 10^9 cells per liter | Standard Deviation 0.3074 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Monocytes: Day 2 | 0.004 10^9 cells per liter | Standard Deviation 0.0752 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Monocytes: follow- up (Day 6) | 0.008 10^9 cells per liter | Standard Deviation 0.0761 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Neutrophils: Day 2 | 0.300 10^9 cells per liter | Standard Deviation 0.4459 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Neutrophils: follow- up (Day 6) | -0.043 10^9 cells per liter | Standard Deviation 0.8141 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Platelets: Day 2 | -3.3 10^9 cells per liter | Standard Deviation 21.12 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Platelets: follow- up (Day 6) | -7.0 10^9 cells per liter | Standard Deviation 21.85 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Reticulocytes: Day 2 | 3.50 10^9 cells per liter | Standard Deviation 5.025 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Reticulocytes: follow- up (Day 6) | 2.51 10^9 cells per liter | Standard Deviation 7.248 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Leukocytes: follow- up (Day 6) | -0.10 10^9 cells per liter | Standard Deviation 0.857 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Lymphocytes: Day 2 | -0.055 10^9 cells per liter | Standard Deviation 0.1099 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Lymphocytes: follow- up (Day 6) | 0.046 10^9 cells per liter | Standard Deviation 0.1994 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Platelets: follow- up (Day 6) | -12.0 10^9 cells per liter | Standard Deviation 9.8 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Monocytes: Day 2 | 0.009 10^9 cells per liter | Standard Deviation 0.093 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Monocytes: follow- up (Day 6) | 0.071 10^9 cells per liter | Standard Deviation 0.1173 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Reticulocytes: follow- up (Day 6) | -3.14 10^9 cells per liter | Standard Deviation 4.541 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Neutrophils: Day 2 | -0.186 10^9 cells per liter | Standard Deviation 0.4348 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Basophils: Day 2 | -0.005 10^9 cells per liter | Standard Deviation 0.0107 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Reticulocytes: Day 2 | -1.97 10^9 cells per liter | Standard Deviation 9.358 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Basophils: follow- up (Day 6) | 0.004 10^9 cells per liter | Standard Deviation 0.0119 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Neutrophils: follow- up (Day 6) | -0.169 10^9 cells per liter | Standard Deviation 0.7111 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Eosinophils: Day 2 | -0.025 10^9 cells per liter | Standard Deviation 0.0568 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Eosinophils: follow- up (Day 6) | -0.040 10^9 cells per liter | Standard Deviation 0.0518 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Leukocytes: Day 2 | -0.28 10^9 cells per liter | Standard Deviation 0.504 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Platelets: Day 2 | -16.5 10^9 cells per liter | Standard Deviation 13.72 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Neutrophils: Day 2 | -0.744 10^9 cells per liter | Standard Deviation 0.9999 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Leukocytes: follow- up (Day 6) | -0.66 10^9 cells per liter | Standard Deviation 1.265 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Platelets: Day 2 | -27.3 10^9 cells per liter | Standard Deviation 18.73 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Eosinophils: Day 2 | 0.010 10^9 cells per liter | Standard Deviation 0.065 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Lymphocytes: Day 2 | 0.141 10^9 cells per liter | Standard Deviation 0.3541 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Reticulocytes: follow- up (Day 6) | 4.76 10^9 cells per liter | Standard Deviation 10.136 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Basophils: Day 2 | -0.003 10^9 cells per liter | Standard Deviation 0.0175 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Lymphocytes: follow- up (Day 6) | 0.024 10^9 cells per liter | Standard Deviation 0.29 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Neutrophils: follow- up (Day 6) | -0.659 10^9 cells per liter | Standard Deviation 1.1235 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Leukocytes: Day 2 | -0.68 10^9 cells per liter | Standard Deviation 1.074 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Monocytes: Day 2 | -0.076 10^9 cells per liter | Standard Deviation 0.1905 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Platelets: follow- up (Day 6) | -22.3 10^9 cells per liter | Standard Deviation 23.89 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Basophils: follow- up (Day 6) | 0.006 10^9 cells per liter | Standard Deviation 0.0119 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Monocytes: follow- up (Day 6) | -0.033 10^9 cells per liter | Standard Deviation 0.1618 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Eosinophils: follow- up (Day 6) | 0.016 10^9 cells per liter | Standard Deviation 0.1051 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets and Reticulocytes | Reticulocytes: Day 2 | -5.01 10^9 cells per liter | Standard Deviation 7.052 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Basophils/Leukocytes: Day 2 | -0.16 percentage of cells | Standard Deviation 0.185 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Basophils/Leukocytes: follow- up (Day 6) | -0.08 percentage of cells | Standard Deviation 0.212 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Eosinophils/Leukocytes: Day 2 | -0.33 percentage of cells | Standard Deviation 1.285 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Eosinophils/Leukocytes: follow- up (Day 6) | -0.04 percentage of cells | Standard Deviation 0.924 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Lymphocytes/Leukocytes: Day 2 | 0.95 percentage of cells | Standard Deviation 3.575 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Lymphocytes/Leukocytes: follow- up (Day 6) | 1.49 percentage of cells | Standard Deviation 6.414 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Monocytes/Leukocytes: Day 2 | -0.59 percentage of cells | Standard Deviation 1.034 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Monocytes/Leukocytes: follow- up (Day 6) | -0.11 percentage of cells | Standard Deviation 0.989 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Neutrophils/Leukocytes: Day 2 | 0.12 percentage of cells | Standard Deviation 4.556 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Neutrophils/Leukocytes: follow- up (Day 6) | -1.26 percentage of cells | Standard Deviation 7.166 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Reticulocytes/Erythrocyte: Day 2 | 0.076 percentage of cells | Standard Deviation 0.1131 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Reticulocytes/Erythrocyte: follow- up (Day 6) | 0.085 percentage of cells | Standard Deviation 0.164 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Reticulocytes/Erythrocyte: follow- up (Day 6) | 0.006 percentage of cells | Standard Deviation 0.1314 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Basophils/Leukocytes: Day 2 | -0.04 percentage of cells | Standard Deviation 0.207 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Monocytes/Leukocytes: Day 2 | 0.39 percentage of cells | Standard Deviation 1.578 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Neutrophils/Leukocytes: Day 2 | 0.11 percentage of cells | Standard Deviation 3.328 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Basophils/Leukocytes: follow- up (Day 6) | 0.06 percentage of cells | Standard Deviation 0.283 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Lymphocytes/Leukocytes: follow- up (Day 6) | 1.25 percentage of cells | Standard Deviation 2.968 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Reticulocytes/Erythrocyte: Day 2 | 0.008 percentage of cells | Standard Deviation 0.1978 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Eosinophils/Leukocytes: Day 2 | -0.29 percentage of cells | Standard Deviation 0.933 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Monocytes/Leukocytes: follow- up (Day 6) | 1.33 percentage of cells | Standard Deviation 1.433 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Lymphocytes/Leukocytes: Day 2 | -0.18 percentage of cells | Standard Deviation 1.689 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Eosinophils/Leukocytes: follow- up (Day 6) | -0.45 percentage of cells | Standard Deviation 0.802 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Neutrophils/Leukocytes: follow- up (Day 6) | -2.19 percentage of cells | Standard Deviation 4.008 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Eosinophils/Leukocytes: follow- up (Day 6) | 0.50 percentage of cells | Standard Deviation 1.379 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Lymphocytes/Leukocytes: Day 2 | 3.66 percentage of cells | Standard Deviation 6.029 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Neutrophils/Leukocytes: follow- up (Day 6) | -3.54 percentage of cells | Standard Deviation 7.499 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Lymphocytes/Leukocytes: follow- up (Day 6) | 2.26 percentage of cells | Standard Deviation 4.562 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Monocytes/Leukocytes: Day 2 | 0.04 percentage of cells | Standard Deviation 1.55 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Monocytes/Leukocytes: follow- up (Day 6) | 0.56 percentage of cells | Standard Deviation 2.042 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Reticulocytes/Erythrocyte: Day 2 | -0.083 percentage of cells | Standard Deviation 0.1581 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Basophils/Leukocytes: Day 2 | 0.01 percentage of cells | Standard Deviation 0.323 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Basophils/Leukocytes: follow- up (Day 6) | 0.21 percentage of cells | Standard Deviation 0.348 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Neutrophils/Leukocytes: Day 2 | -4.02 percentage of cells | Standard Deviation 6.968 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Eosinophils/Leukocytes: Day 2 | 0.31 percentage of cells | Standard Deviation 1.249 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes and Reticulocytes/Erythrocytes | Reticulocytes/Erythrocyte: follow- up (Day 6) | 0.210 percentage of cells | Standard Deviation 0.3447 |
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.
Time frame: Baseline, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | Day 2 | 0.14 femtoliters | Standard Deviation 0.983 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | Follow- up (Day 6) | 0.61 femtoliters | Standard Deviation 0.969 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | Day 2 | 0.03 femtoliters | Standard Deviation 1.562 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | Follow- up (Day 6) | 0.54 femtoliters | Standard Deviation 0.94 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | Day 2 | -0.22 femtoliters | Standard Deviation 1.445 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume | Follow- up (Day 6) | -0.19 femtoliters | Standard Deviation 0.662 |
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.
Time frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Day 2 | 11.3 beats per minute | Standard Deviation 5.18 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Day 1 | 1.1 beats per minute | Standard Deviation 2.42 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Follow-up (Day 6) | 11.0 beats per minute | Standard Deviation 8.07 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Day 2 | 7.4 beats per minute | Standard Deviation 7.78 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Day 1 | 1.5 beats per minute | Standard Deviation 8.26 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Follow-up (Day 6) | 3.6 beats per minute | Standard Deviation 7.31 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Day 1 | -1.4 beats per minute | Standard Deviation 5.53 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Follow-up (Day 6) | 5.9 beats per minute | Standard Deviation 6.17 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Pulse Rate | Day 2 | 8.8 beats per minute | Standard Deviation 5.34 |
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.
Time frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Day 2 | 1.5 breaths per minute | Standard Deviation 2.33 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Day 1 | -1.0 breaths per minute | Standard Deviation 1.69 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Follow-up (Day 6) | 1.0 breaths per minute | Standard Deviation 3.02 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Day 2 | 0.0 breaths per minute | Standard Deviation 1.51 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Day 1 | 0.9 breaths per minute | Standard Deviation 1.64 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Follow-up (Day 6) | -0.5 breaths per minute | Standard Deviation 0.93 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Day 1 | -0.6 breaths per minute | Standard Deviation 1.3 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Follow-up (Day 6) | -0.1 breaths per minute | Standard Deviation 1.46 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Respiratory Rate | Day 2 | -0.8 breaths per minute | Standard Deviation 2.43 |
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.
Time frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Day 1 | 3.5 millimeters of mercury (mmHg) | Standard Deviation 12.95 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Day 2 | 5.6 millimeters of mercury (mmHg) | Standard Deviation 6.97 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: follow-up (Day 6) | 0.1 millimeters of mercury (mmHg) | Standard Deviation 15.58 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Day 1 | 1.4 millimeters of mercury (mmHg) | Standard Deviation 6.86 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Day 2 | 1.9 millimeters of mercury (mmHg) | Standard Deviation 4.58 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: follow-up (Day 6) | 1.0 millimeters of mercury (mmHg) | Standard Deviation 7.37 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: follow-up (Day 6) | 3.3 millimeters of mercury (mmHg) | Standard Deviation 4.74 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Day 1 | -3.6 millimeters of mercury (mmHg) | Standard Deviation 3.58 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Day 1 | -3.5 millimeters of mercury (mmHg) | Standard Deviation 7.17 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Day 2 | 0.6 millimeters of mercury (mmHg) | Standard Deviation 5.07 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Day 2 | 4.8 millimeters of mercury (mmHg) | Standard Deviation 13.05 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: follow-up (Day 6) | 4.8 millimeters of mercury (mmHg) | Standard Deviation 5.99 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Day 2 | -1.1 millimeters of mercury (mmHg) | Standard Deviation 8.68 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: follow-up (Day 6) | 0.9 millimeters of mercury (mmHg) | Standard Deviation 13.21 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: follow-up (Day 6) | 0.5 millimeters of mercury (mmHg) | Standard Deviation 7.73 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Day 1 | -2.0 millimeters of mercury (mmHg) | Standard Deviation 4.34 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP: Day 1 | 2.0 millimeters of mercury (mmHg) | Standard Deviation 6.7 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP: Day 2 | -1.9 millimeters of mercury (mmHg) | Standard Deviation 4.52 |
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.
Time frame: Baseline, Day 1, Day 2 and follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Temperature | Day 2 | 0.46 degree celsius | Standard Deviation 0.463 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Temperature | Day 1 | -0.04 degree celsius | Standard Deviation 0.366 |
| Group 1: Normal Hepatic Function (Reference) | Change From Baseline in Vital Sign Parameter: Temperature | Follow-up (Day 6) | 0.21 degree celsius | Standard Deviation 0.223 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Temperature | Day 2 | 0.05 degree celsius | Standard Deviation 0.396 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Temperature | Day 1 | -0.00 degree celsius | Standard Deviation 0.438 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Change From Baseline in Vital Sign Parameter: Temperature | Follow-up (Day 6) | 0.14 degree celsius | Standard Deviation 0.444 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Temperature | Day 1 | -0.01 degree celsius | Standard Deviation 0.27 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Temperature | Follow-up (Day 6) | 0.16 degree celsius | Standard Deviation 0.354 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Change From Baseline in Vital Sign Parameter: Temperature | Day 2 | 0.19 degree celsius | Standard Deviation 0.348 |
Secondary
Fraction of Unbound Drug (fu) of M2951
fu is defined as the ratio of unbound drug concentration to the total drug concentration.
Time frame: 1.5, 4, and 12 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Fraction of Unbound Drug (fu) of M2951 | 5.00 ratio of unbound drug | Geometric Coefficient of Variation 15.3 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Fraction of Unbound Drug (fu) of M2951 | 5.78 ratio of unbound drug | Geometric Coefficient of Variation 17.9 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Fraction of Unbound Drug (fu) of M2951 | 6.55 ratio of unbound drug | Geometric Coefficient of Variation 11.9 |
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.
Time frame: 1.5, 4, and 12 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Maximum Observed Plasma Concentration of Unbound M2951 (Cmax, u) | 3.19 ng/mL | Geometric Coefficient of Variation 22.8 |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Maximum Observed Plasma Concentration of Unbound M2951 (Cmax, u) | 4.57 ng/mL | Geometric Coefficient of Variation 92.6 |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Maximum Observed Plasma Concentration of Unbound M2951 (Cmax, u) | 7.72 ng/mL | Geometric Coefficient of Variation 36.1 |
Comparison: Mild Hepatic Impairment vs Normal Hepatic Function90% CI: [0.86, 2.39]
Comparison: Moderate Hepatic Impairment vs Normal Hepatic Function90% CI: [1.87, 3.14]
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.
Time frame: up to follow-up (Day 6)
Population: SAF included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of M2951
Tmax was obtained directly from the concentration versus time curve.
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Normal Hepatic Function (Reference) | Time to Reach the Maximum Plasma Concentration (Tmax) of M2951 | 2.00 hours |
| Group 2: Mild Hepatic Impairment (Child-Pugh Class A) | Time to Reach the Maximum Plasma Concentration (Tmax) of M2951 | 1.76 hours |
| Group 3: Moderate Hepatic Impairment (Child-Pugh Class B) | Time to Reach the Maximum Plasma Concentration (Tmax) of M2951 | 1.75 hours |