Hepatic Impairment, Liver Diseases
Conditions
Keywords
healthy volunteers
Brief summary
The purpose of this study is to learn how the study medicine (PF-07923568) is processed in participants with liver function loss compared to healthy participants. The different levels of liver function loss can be mild, moderate or severe. This study is seeking participants who: * are male or female of 18 years of age or older. * are examined to be healthy (group with no loss of liver function). * have mild, moderate, and severe liver disease (group with loss of liver function). All participants will receive a one-time dose of 4 capsules of PF-07923568 which will be taken by mouth. All participants will remain at the study clinic for 6 days for safety review and laboratory collections. This is to see how the study medicine is being broken down by the liver over time. All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are examined to see whether they are fit for the study. During this period, the participant's medical history and past and current medications will be reviewed. A series of tests will also be performed to see if they are good to be selected for the study. If the participant meets all required criteria and are interested in continuing, the participant will be brought into the study clinic to stay overnight for 6 days. On day 6, the participant will be discharged. About 28 to 35 days after discharge, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to conclude the study.
Interventions
DRUGPF-07923568
One time dose of 4 capsules taken orally.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
An open-label, single dose, parallel group, multicenter study to investigate the effect of varying degrees of hepatic function on the plasma PK of PF-07923568 after a single, oral 200 mg dose administered in the fed state (standard breakfast).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
for healthy volunteers: * BMI of 17.5 to 38.0 kg/m2, inclusive, and a total body weight \>50 kg (110 lb). * Capable of giving signed informed consent. * At screening, no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, including BP and pulse rate measurement, standard 12-lead ECG and clinical laboratory tests. * body weight within +/-15 kg of the average of pooled hepatic impaired group and +/- 10 years of the average pooled hepatic impairment group. --
Exclusion criteria
for all participants: * Any condition or surgery possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection) * Positive HIV antibodies * Positive drug or alcohol test eGFR \<60 mL/min/1.73m2 at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose | Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6 | Cmax was the highest concentration observed directly from data |
| Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose | Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6 | AUClast was determined using linear/Log trapezoidal method |
| Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose | Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6 | AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminalphase rate constant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Day -1 through follow-up (Day 29-36) | Adverse event (AE) was any untoward medical occurrence in the participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious AE was any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was considered to be an important medical event. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent. AEs included both serious and non-serious AEs. |
| Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | Day -1, Day 1, Day 2, and Day 6 | Number of participants with ECG findings meeting the following criteria: time between the onset of atrial depolarization and onset of ventricular depolarization (PR interval) ≥300 msec; time from ECG Q-wave to the end of the S wave corresponding to ventricular depolarization (QRS duration) ≥140 msec; correct time from ECG Q-wave to the end of the T wave corresponding to electrical systole for heart rate using Fridericia's formula (QTcF interval): ≥450 to \<480 msec; QTcF interval ≥480 to \<500 msec; QTcF interval: ≥500 msec; PR interval percent change from baseline (≥25/50%): ≥25% if baseline \>200 msec or ≥ 50% if baseline ≤200 msec; QRS duration percent change from baseline ≥50%; QTcF interval change from baseline: \>30 to ≤60 msec; QTcF interval change from baseline \>60 msec. The baseline measurement was the predose measurement on Day 1. Changes from baseline was defined as the change between the postdose and baseline measurements. |
| Number of Participants With Laboratory Test Abnormalities | Day -1 and Day 6 | Laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute and percent total neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin and total protein), urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy, urinary albumin to creatinine ratio and urinary protein to creatinine ratio) and other tests. Abnormality was determined by the investigator. Only lab abnormalities with at least 1 occurrence in participants are reported. |
| Number of Participants With Vital Signs Meeting Categorical Criteria | Day -1, Day 1, Day 2, and Day 6 | Supine blood pressure and pulse rate were measured. Categorical classes for vital signs of potential clinical concerns were defined as followed: systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); diastolic blood pressure (DBP) \<50 mmHg; pulse rate \<40 beats per minute (bpm); pulse rate \>120 bpm, and increase from baseline in SBP ≥30 mmHg; decrease from baseline in SBP ≥30 mmHg; increase from baseline in DBP ≥20 mmHg; decrease from baseline in DBP ≥20 mmHg. The baseline measurement was the predose measurement on Day 1. Changes from baseline was defined as the change between the postdose and baseline measurements. |
Countries
United States
Participant flow
Recruitment details
Participants with varying degrees of hepatic function were enrolled in 4 groups
Participants by arm
| Arm | Count |
|---|---|
| No Hepatic Impairment Participants received an oral single dose of sisunatovir 200 mg (4 × 50 mg capsules) with the morning meal. | 8 |
| Mild Hepatic Impairment Participants received an oral single dose of sisunatovir 200 mg (4 × 50 mg capsules) with the morning meal. | 8 |
| Moderate Hepatic Impairment Participants received an oral single dose of sisunatovir 200 mg (4 × 50 mg capsules) with the morning meal. | 8 |
| Severe Hepatic Impairment Participants received an oral single dose of sisunatovir 200 mg (4 × 50 mg capsules) with the morning meal. | 4 |
| Total | 28 |
Baseline characteristics
| Characteristic | No Hepatic Impairment | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Total |
|---|---|---|---|---|---|
| Age, Customized 18-44 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Age, Customized 45-64 years | 7 Participants | 3 Participants | 6 Participants | 2 Participants | 18 Participants |
| Age, Customized ≥65 years | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 7 Participants | 5 Participants | 5 Participants | 1 Participants | 18 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 1 / 8 | 0 / 8 | 1 / 8 | 1 / 4 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 4 |
Outcome results
Primary
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose
AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminalphase rate constant.
Time frame: Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6
Population: All participants who received at least 1 dose of sisunatovir and had at least 1 of the pharmacokenetic parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| No Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose | 922.6 ng*hr/mL | Geometric Coefficient of Variation 35 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose | 765.6 ng*hr/mL | Geometric Coefficient of Variation 68 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose | 1213 ng*hr/mL | Geometric Coefficient of Variation 95 |
| Severe Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose | 3617 ng*hr/mL | Geometric Coefficient of Variation 19 |
90% CI: [50.53, 136.28]
90% CI: [80.09, 215.99]
90% CI: [213.57, 719.85]
Primary
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose
AUClast was determined using linear/Log trapezoidal method
Time frame: Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6
Population: All participants who received at least 1 dose of sisunatovir and had at least 1 of the pharmacokenetic parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| No Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose | 891.6 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose | 732.6 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 70 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose | 1166 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 99 |
| Severe Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose | 3437 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
90% CI: [49.24, 137.11]
90% CI: [78.4, 218.3]
90% CI: [205.92, 721.77]
Primary
Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose
Cmax was the highest concentration observed directly from data
Time frame: Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6
Population: All participants who received at least 1 dose of sisunatovir and had at least 1 of the pharmacokenetic parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| No Hepatic Impairment | Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose | 81.25 Nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 57 |
| Mild Hepatic Impairment | Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose | 68.52 Nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| Moderate Hepatic Impairment | Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose | 73.85 Nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| Severe Hepatic Impairment | Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose | 127.8 Nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
90% CI: [50.94, 139.59]
90% CI: [54.91, 150.45]
90% CI: [84.81, 291.49]
Secondary
Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs
Adverse event (AE) was any untoward medical occurrence in the participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious AE was any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was considered to be an important medical event. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent. AEs included both serious and non-serious AEs.
Time frame: Day -1 through follow-up (Day 29-36)
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| No Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | All-causality TEAEs | 1 Participants |
| No Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Serious TEAEs | 0 Participants |
| No Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Treatment-related TEAEs | 1 Participants |
| No Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Discontinuations from study due to TEAEs | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Serious TEAEs | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Treatment-related TEAEs | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Discontinuations from study due to TEAEs | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | All-causality TEAEs | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Treatment-related TEAEs | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Serious TEAEs | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Discontinuations from study due to TEAEs | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | All-causality TEAEs | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Discontinuations from study due to TEAEs | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Serious TEAEs | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | All-causality TEAEs | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs | Treatment-related TEAEs | 0 Participants |
Secondary
Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria
Number of participants with ECG findings meeting the following criteria: time between the onset of atrial depolarization and onset of ventricular depolarization (PR interval) ≥300 msec; time from ECG Q-wave to the end of the S wave corresponding to ventricular depolarization (QRS duration) ≥140 msec; correct time from ECG Q-wave to the end of the T wave corresponding to electrical systole for heart rate using Fridericia's formula (QTcF interval): ≥450 to \<480 msec; QTcF interval ≥480 to \<500 msec; QTcF interval: ≥500 msec; PR interval percent change from baseline (≥25/50%): ≥25% if baseline \>200 msec or ≥ 50% if baseline ≤200 msec; QRS duration percent change from baseline ≥50%; QTcF interval change from baseline: \>30 to ≤60 msec; QTcF interval change from baseline \>60 msec. The baseline measurement was the predose measurement on Day 1. Changes from baseline was defined as the change between the postdose and baseline measurements.
Time frame: Day -1, Day 1, Day 2, and Day 6
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| No Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥450 msec to <480 msec | 0 Participants |
| No Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥480 msec to <500 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥480 msec to <500 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥450 msec to <480 msec | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥450 msec to <480 msec | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥480 msec to <500 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥450 msec to <480 msec | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria | QTcF interval: ≥480 msec to <500 msec | 1 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute and percent total neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin and total protein), urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy, urinary albumin to creatinine ratio and urinary protein to creatinine ratio) and other tests. Abnormality was determined by the investigator. Only lab abnormalities with at least 1 occurrence in participants are reported.
Time frame: Day -1 and Day 6
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention, and who had at least one observation of the given laboratory test and had a laboratory abnormality meeting specified criteria while on study treatment or during lag time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | pH >8 | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Volume >1.1 x upper limit of normal (ULN) | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | URINE Glucose ≥1 | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Urobilinogen ≥1 | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Neutrophils < 0.8 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Erythrocytes <0.8 x lower limit of normal (LLN) | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Nitrite ≥1 | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Direct Bilirubin > 1.5 x ULN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Indirect Bilirubin >1.5 x ULN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Activated Partial Thromboplastin Time >1.1 x ULN | 3 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Lymphocytes <0.8 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase >3.0 x ULN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Intl. Normalized Ratio >1.1 x ULN | 1 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Albumin <0.8 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Platelets <0.5 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Potassium <0.9 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Time >1.1 x ULN | 1 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bicarbonate <0.9 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Hemoglobin Concentration <0.9 x LLN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Glucose - FASTING >1.5 x ULN | 0 Participants |
| No Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bilirubin >1.5 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Potassium <0.9 x LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | pH >8 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bilirubin >1.5 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Glucose - FASTING >1.5 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase >3.0 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | URINE Glucose ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Time >1.1 x ULN | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Erythrocytes <0.8 x lower limit of normal (LLN) | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Hemoglobin Concentration <0.9 x LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Urobilinogen ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Platelets <0.5 x LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Volume >1.1 x upper limit of normal (ULN) | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Albumin <0.8 x LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Nitrite ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Intl. Normalized Ratio >1.1 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Direct Bilirubin > 1.5 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Activated Partial Thromboplastin Time >1.1 x ULN | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Lymphocytes <0.8 x LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bicarbonate <0.9 x LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Indirect Bilirubin >1.5 x ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Neutrophils < 0.8 x LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Activated Partial Thromboplastin Time >1.1 x ULN | 5 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Time >1.1 x ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Intl. Normalized Ratio >1.1 x ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bilirubin >1.5 x ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Direct Bilirubin > 1.5 x ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Indirect Bilirubin >1.5 x ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase >3.0 x ULN | 3 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Albumin <0.8 x LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Potassium <0.9 x LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bicarbonate <0.9 x LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Glucose - FASTING >1.5 x ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | pH >8 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | URINE Glucose ≥1 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Urobilinogen ≥1 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Nitrite ≥1 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Erythrocytes <0.8 x lower limit of normal (LLN) | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Volume >1.1 x upper limit of normal (ULN) | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Hemoglobin Concentration <0.9 x LLN | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Platelets <0.5 x LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Lymphocytes <0.8 x LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Neutrophils < 0.8 x LLN | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Nitrite ≥1 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Volume >1.1 x upper limit of normal (ULN) | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bicarbonate <0.9 x LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Potassium <0.9 x LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Neutrophils < 0.8 x LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Ery. Mean Corpuscular Hemoglobin Concentration <0.9 x LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Albumin <0.8 x LLN | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase >3.0 x ULN | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Time >1.1 x ULN | 4 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Platelets <0.5 x LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Indirect Bilirubin >1.5 x ULN | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Direct Bilirubin > 1.5 x ULN | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Activated Partial Thromboplastin Time >1.1 x ULN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Lymphocytes <0.8 x LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Bilirubin >1.5 x ULN | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Urobilinogen ≥1 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | URINE Glucose ≥1 | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Prothrombin Intl. Normalized Ratio >1.1 x ULN | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Erythrocytes <0.8 x lower limit of normal (LLN) | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | pH >8 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Laboratory Test Abnormalities | Glucose - FASTING >1.5 x ULN | 0 Participants |
Secondary
Number of Participants With Vital Signs Meeting Categorical Criteria
Supine blood pressure and pulse rate were measured. Categorical classes for vital signs of potential clinical concerns were defined as followed: systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); diastolic blood pressure (DBP) \<50 mmHg; pulse rate \<40 beats per minute (bpm); pulse rate \>120 bpm, and increase from baseline in SBP ≥30 mmHg; decrease from baseline in SBP ≥30 mmHg; increase from baseline in DBP ≥20 mmHg; decrease from baseline in DBP ≥20 mmHg. The baseline measurement was the predose measurement on Day 1. Changes from baseline was defined as the change between the postdose and baseline measurements.
Time frame: Day -1, Day 1, Day 2, and Day 6
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| No Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: increase from baseline ≥20 mmHg | 0 Participants |
| No Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: decrease from baseline ≥20 mmHg | 0 Participants |
| No Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP <90 mmHg | 1 Participants |
| No Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP: increase from baseline ≥30 mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: decrease from baseline ≥20 mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP <90 mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP: increase from baseline ≥30 mmHg | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: increase from baseline ≥20 mmHg | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP <90 mmHg | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: decrease from baseline ≥20 mmHg | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP: increase from baseline ≥30 mmHg | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: increase from baseline ≥20 mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP: increase from baseline ≥30 mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: decrease from baseline ≥20 mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | DBP: increase from baseline ≥20 mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Meeting Categorical Criteria | SBP <90 mmHg | 0 Participants |