Hepatic Impairment
Conditions
Keywords
COVID-19, SARS-CoV-2
Brief summary
The study is to estimate the effect of hepatic impairment on the plasma PK of PF-07321332/ritonavir. Findings from this study will be used to develop dosing recommendations so that the dose and/or dosing interval may be adjusted appropriately in the presence of hepatic impairment.
Interventions
DRUGPF-07321332
Tablet
DRUGRitonavir
PK Boosting agent
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants who are classically healthy having no clinically relevant abnormalities. No known or suspected hepatic impairment * Stable hepatic impairment that meets the criteria for Class B of the Child-Pugh Classification
Exclusion criteria
* Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection). * Participants who have been vaccinated with COVID-19 vaccines within the past week of dosing * A positive urine drug test, for illicit drugs, at Screening * History of sensitivity reactions to ritonavir or any of the formulation components of PF-07321332 or ritonavir. * eGFR \<60 mL/min/1.73m2 based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥ upper limit of normal (ULN) (for healthy participants); AST or ALT \> 5x ULN (for hepatic impairment participants) * Albumin \> ULN (for healthy participants); * Prothrombin time \> ULN (for healthy participants); * Total bilirubin level ≥1.5 × ULN \[NOTE: Participants with a history of Gilbert syndrome (and hence elevated total bilirubin) are eligible provided direct bilirubin level is ≤ ULN).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332 | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours | Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation was expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332 | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours | AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332 | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation was expressed in percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Treatment Emergent Adverse Event (TEAE) | Up to 2 months | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. |
| Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | Up to 2 months | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology; clinical chemistry; urinalysis. |
| Number of Participants With Abnormal Electrocardiograms (ECGs) | Up to 2 months | ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline. |
| Number of Participants With Abnormal Vital Signs | Up to 2 months | Criteria for vital signs abnormalities: increase or decrease from baseline in systolic blood pressure (SBP) \>=30 mm Hg and increase or decrease from baseline in diastolic blood pressure (DBP) \>=20 mm Hg; the value of SBP \<90 mm Hg; the value of DBP \<50 mm Hg; the value of pulse rate \<40 bpm or \>120 bpm. |
Countries
United States
Participant flow
Pre-assignment details
Seventeen participants were assigned to treatment. One participant in the moderate hepatic impairment group was excluded from the safety and pharmacokinetic (PK) analysis set as this participant was randomized but was discontinued on Day 1 prior to dosing with study treatment PF-07321332. All 16 treated participants included 8 participants without hepatic impairment (Cohort 1) and 8 participants with moderate hepatic impairment (Cohort 2) completed the study.,
Participants by arm
| Arm | Count |
|---|---|
| Normal Hepatic Function Participants with normal hepatic function and matched, by average age, weight, and gender as much as practically possible with participants with moderate hepatic impairment. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. | 8 |
| Moderate Hepatic Impairment Moderate Hepatic Impairment: Participants with moderate hepatic impairment (grade B) with a Child-Pugh Score of 7-9. The CP classification assesses 5 hepatic parameters (serum total bilirubin, serum albumin, prothrombin time prolongation, ascites, and encephalopathy grade) on a scale of 1 to 3 (most severe derangement). Total moderate hepatic impairment score range is 7 to 9. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Enrolled, but not treated | 0 | 1 |
Baseline characteristics
| Characteristic | Moderate Hepatic Impairment | Total | Normal Hepatic Function |
|---|---|---|---|
| Age, Continuous | 56.1 Years STANDARD_DEVIATION 9.33 | 54.4 Years STANDARD_DEVIATION 7.83 | 52.8 Years STANDARD_DEVIATION 6.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 3 / 8 | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation was expressed in percentage.
Time frame: Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours
Population: The PK parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332 | 15.24 ug*hr/mL | Geometric Coefficient of Variation 36 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332 | 15.06 ug*hr/mL | Geometric Coefficient of Variation 43 |
90% CI: [70.65, 138.12]ANOVA
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332
AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage.
Time frame: Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours
Population: The PK parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332 | 14.97 micrograms/milliliter/hour (ug*hr/mL) | Geometric Coefficient of Variation 36 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332 | 14.86 micrograms/milliliter/hour (ug*hr/mL) | Geometric Coefficient of Variation 43 |
90% CI: [70.81, 139.21]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332
Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation was expressed in percentage.
Time frame: Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours
Population: The PK parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332 | 1.886 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 20 |
| Moderate Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332 | 1.923 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 48 |
90% CI: [74.2, 140.11]ANOVA
Secondary
Number of Participants With Abnormal Electrocardiograms (ECGs)
ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline.
Time frame: Up to 2 months
Population: Population analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QT INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 30 < Change ≤ 60 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 25/50% | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Change > 60 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 50% | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 30 < Change ≤ 60 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): Change > 60 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): Change > 60 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 25/50% | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 50% | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QT INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 30 < Change ≤ 60 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Change > 60 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 30 < Change ≤ 60 | 0 Participants |
Secondary
Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality)
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology; clinical chemistry; urinalysis.
Time frame: Up to 2 months
Population: Population analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Calcium (mg/dL) >1.1× ULN | 1 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL) >1.5× ULN | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3) >1.2× upper limit of normal (ULN) | 1 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin ≥1 | 1 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Direct Bilirubin (mg/dL) >1.5× ULN | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: Urobilinogen ≥1 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | HEMATOLOGY: Platelets (10^3/mm^3) <0.5× lower limit of normal (LLN) | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: Leukocyte Esterase ≥1 | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L) >3.0× ULN | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: Urine Microscopic Exam ≥1 | 1 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) >1.2× ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: Urine Microscopic Exam ≥1 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | HEMATOLOGY: Platelets (10^3/mm^3) <0.5× lower limit of normal (LLN) | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3) >1.2× upper limit of normal (ULN) | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) >1.2× ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Direct Bilirubin (mg/dL) >1.5× ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L) >3.0× ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL) >1.5× ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin ≥1 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: Urobilinogen ≥1 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | URINALYSIS: Leukocyte Esterase ≥1 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Calcium (mg/dL) >1.1× ULN | 0 Participants |
Secondary
Number of Participants With Abnormal Vital Signs
Criteria for vital signs abnormalities: increase or decrease from baseline in systolic blood pressure (SBP) \>=30 mm Hg and increase or decrease from baseline in diastolic blood pressure (DBP) \>=20 mm Hg; the value of SBP \<90 mm Hg; the value of DBP \<50 mm Hg; the value of pulse rate \<40 bpm or \>120 bpm.
Time frame: Up to 2 months
Population: Population analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | DBP: Change >= 20 mmHg increase from baseline | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | SBP: Change >= 30 mmHg decrease from baseline | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | DBP: Change >= 20 mmHg decrease from baseline | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | SBP: Value <90mmHg | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | Pulse Rate: Value <40 bpm | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | DBP: Value <50 mmHg | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | Pulse Rate: Value >120 bpm | 0 Participants |
| Normal Hepatic Function | Number of Participants With Abnormal Vital Signs | SBP: Change >= 30 mmHg increase from baseline | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | Pulse Rate: Value >120 bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | SBP: Value <90mmHg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | SBP: Change >= 30 mmHg decrease from baseline | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | DBP: Value <50 mmHg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | DBP: Change >= 20 mmHg increase from baseline | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | DBP: Change >= 20 mmHg decrease from baseline | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | Pulse Rate: Value <40 bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Abnormal Vital Signs | SBP: Change >= 30 mmHg increase from baseline | 1 Participants |
Secondary
Number of Participants With an Treatment Emergent Adverse Event (TEAE)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.
Time frame: Up to 2 months
Population: Population analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With an Treatment Emergent Adverse Event (TEAE) | Participants with adverse events (All Causalities) | 3 Participants |
| Normal Hepatic Function | Number of Participants With an Treatment Emergent Adverse Event (TEAE) | Participants with adverse events (Treatment Related) | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With an Treatment Emergent Adverse Event (TEAE) | Participants with adverse events (All Causalities) | 4 Participants |
| Moderate Hepatic Impairment | Number of Participants With an Treatment Emergent Adverse Event (TEAE) | Participants with adverse events (Treatment Related) | 3 Participants |