Healthy Volunteers, Hepatic Impairment
Conditions
Keywords
Hepatic impairment, Healthy volunteers
Brief summary
The purpose of this study is to understand the effects of liver functional impairment on the study medicine (PF-07081532). People with liver functional impairment may process the study medicine differently from healthy people. We are seeking participants who: * Are between 18 and 70 years of age; * Have a BMI (body mass index) of 17.5 to 38.0 kg/m2, inclusive, and a total body weight \>50 kg (110 lbs.). Participants will take the study medicine as a tablet once at the study clinic, and then will stay onsite for about 7 days. During this time, the study team will monitor their treatment experience and take some blood samples to test the level of PF-07081532. This will help us understand if certain level of liver functional impairment could affect the study medicine being processed in the body.
Interventions
DRUGPF-07081532
PF-07081532 20 milligrams (mg), 1 tablet orally, once on Day 1
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female between the ages of 18 and 70 years, inclusive at the screening visit. * Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. * BMI of 17.5 to 38.0 kg/m2, inclusive, and a total body weight \>50 kg (110 lb). * Group 1 only: at screening, no clinically relevant abnormalities identified by a detailed medical history, physical exam, including blood pressure and pulse rate measurement, ECG and clinical laboratory tests. * Group 1 only: no known or suspected hepatic impairment and meet the criteria based on screening laboratory liver function tests. * Groups 2, 3 & 4 only: stable hepatic impairment that meets criteria for Class A, B, or C of the Child-Pugh classification with no clinically significant change in disease status within 28 days before screening. * Groups 2, 3 & 4 only: stable concomitant medications for the management of individual participant's medical history.
Exclusion criteria
* Any condition possibly affecting drug absorption * At screening, a positive result for HIV antibodies. * Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or participants with suspected MTC per study doctor's judgement. * History of acute pancreatitis within 6 months before the screening visit or any history of chronic pancreatitis. * Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study. * Use of specific prohibited prior/concomitant therapies * Use of an investigational product within 30 days (or local requirement) or 5 half-lives (whichever longer). * eGFR\<60 mL/min/1.73m2 at screening. * A positive urine drug test at screening or admission to study clinic. * At screening or admission to study clinic, a positive breath alcohol test. * For females, pregnancy, as indicated by a positive serum pregnancy test at screening and/or positive urine pregnancy test in women capable of having children at admission to study clinic * Group 1 only: evidence of chronic liver disease including history of hepatitis, hepatitis B, or hepatitis C. * Group 1 only: history of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of screening. * Group 1 only: screening ECG demonstrating QTcF interval \>450 ms or a QRS interval \>120 ms. * Group 1 only: screening seated systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg * Group 1 only: use of chronic prescription medications within 7 days or 5 half-lives (whichever longer) before Day 1, or for prohibited medications, use within the required washout/restriction period. * Group 2, 3 & 4 only: Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as \<1 year in Groups 2 & 3 and \<6 months for Group 4 only). * Group 2, 3 & 4 only: a diagnosis of hepatic dysfunction secondary to any acute ongoing hepatocellular process that is documented by medical history, physical exam, liver biopsy, hepatic ultrasound, CT scan, or MRI. * Group 2, 3 & 4 only: history of surgery that would be expected to alter absorption, distribution, metabolism, or excretion properties of PF-07081532. * Group 2, 3 & 4 only: history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 4 weeks prior to screening. * Group 2, 3 & 4 only: signs of clinically active Grade 3 or 4 hepatic encephalopathy * Groups 2, 3 & 4 only: severe ascites and/or pleural effusion, except for those categorized in Group 4 who may be enrolled provided participant is medically stable, per the study doctor's judgment. * Groups 2, 3 & 4 only: previously received a kidney, liver, or heart transplant. * Groups 2, 3, & 4 only: screening ECG demonstrating a QTcF interval \>470 ms or a QRS interval \>120 ms. * Groups 2, 3 & 4 only: at screening, admission to study clinic or pre-dose on Day 1, persistent severe, uncontrolled hypertension. * Groups 2, 3 & 4 only: ALT or AST \>5x upper limit of normal on clinical laboratory tests at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unbound AUClast (AUClast,u) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | AUClast,u is the unbound AUClast. |
| Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | AUClast is the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration. |
| Fraction of Unbound Drug in Plasma (Fu) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | Fu is the fraction of unbound drug in plasma, which is calculated by Cu/C (where Cu represents unbound concentration and C represents total concentration). |
| Unbound Cmax (Cmax,u) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | Cmax,u is the unbound Cmax. |
| Unbound AUCinf (AUCinf,u) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | AUCinf,u is the unbound AUCinf. |
| Maximum Plasma Concentration (Cmax) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | Cmax is the maximum plasma concentration. |
| Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532 | At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1 | AUCinf is the area under the plasma concentration-time profile from time zero extrapolated to infinite time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | From baseline (BL) to Day 7 | Safety laboratory assessments included clinical chemistry, hematology, and urinalysis tests. Number of participants with clinical laboratory abnormalities meeting pre-specified criteria is reported. |
| Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | From BL to Day 7 | Vital signs abnormalities included: seated diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg or absolute value \<50mmHg; systolic BP increase and decrease from BL of \>=30mmHg or absolute value \<90mmHg; pulse rate \<40 or \>120bpm. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | From BL to Day 7 | ECG assessments included PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities included PR interval BL \>200msec and max ≥25% increase from BL, or BL ≤200msec and max ≥50% increase from BL, or absolute value ≥300msec; QRS interval percent change from BL ≥50% or absolute value ≥140msec; QTcF change from BL 30- ≤60msec, \>60msec, or absolute value 450- ≤480msec, 480- ≤500msec, or \>500msec. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Day 1 to Day 36 | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were defined as events that started during the effective duration of treatment (ie, starting on or after the dose of PF-07081532 up to the final follow-up visit). AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. |
Countries
United States
Participant flow
Pre-assignment details
A total of 39 participants were screened, of whom 24 participants were assigned to treatment and treated, with 6 participants in each group (without hepatic impairment, with mild hepatic impairment, with moderate hepatic impairment, and with severe hepatic impairment).
Participants by arm
| Arm | Count |
|---|---|
| Without Hepatic Impairment This arm included participants without hepatic impairment who received PF-07081532 20mg on Day 1. | 6 |
| Mild Hepatic Impairment This arm included participants with mild hepatic impairment who received PF-07081532 20mg on Day 1. | 6 |
| Moderate Hepatic Impairment This arm included participants with moderate hepatic impairment who received PF-07081532 20mg on Day 1. | 6 |
| Severe Hepatic Impairment This arm included participants with severe hepatic impairment who received PF-07081532 20mg on Day 1. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Without 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 | 6 Participants | 3 Participants | 2 Participants | 5 Participants | 16 Participants |
| Age, Customized >=65 years | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity not reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 Participants | 4 Participants | 5 Participants | 3 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 4 Participants | 5 Participants | 18 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 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532
AUCinf is the area under the plasma concentration-time profile from time zero extrapolated to infinite time.
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532 | 43200 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532 | 44010 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 61 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532 | 67430 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| Severe Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532 | 41680 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 62 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [59.74, 173.71]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [91.53, 266.14]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [56.58, 164.51]ANOVA
Primary
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532
AUClast is the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration.
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | 40990 ng*hr/mL | Geometric Coefficient of Variation 39 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | 41900 ng*hr/mL | Geometric Coefficient of Variation 63 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | 62680 ng*hr/mL | Geometric Coefficient of Variation 64 |
| Severe Hepatic Impairment | Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532 | 39800 ng*hr/mL | Geometric Coefficient of Variation 63 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [59.91, 174.39]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [89.62, 260.9]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [56.9, 165.65]ANOVA
Primary
Fraction of Unbound Drug in Plasma (Fu) of PF-07081532
Fu is the fraction of unbound drug in plasma, which is calculated by Cu/C (where Cu represents unbound concentration and C represents total concentration).
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Fraction of Unbound Drug in Plasma (Fu) of PF-07081532 | 0.0002753 Ratio | Geometric Coefficient of Variation 12 |
| Mild Hepatic Impairment | Fraction of Unbound Drug in Plasma (Fu) of PF-07081532 | 0.0002568 Ratio | Geometric Coefficient of Variation 38 |
| Moderate Hepatic Impairment | Fraction of Unbound Drug in Plasma (Fu) of PF-07081532 | 0.0002937 Ratio | Geometric Coefficient of Variation 19 |
| Severe Hepatic Impairment | Fraction of Unbound Drug in Plasma (Fu) of PF-07081532 | 0.0006780 Ratio | Geometric Coefficient of Variation 66 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [64.61, 134.69]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [73.89, 154.03]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [170.57, 355.58]ANOVA
Primary
Maximum Plasma Concentration (Cmax) of PF-07081532
Cmax is the maximum plasma concentration.
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Maximum Plasma Concentration (Cmax) of PF-07081532 | 2236 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| Mild Hepatic Impairment | Maximum Plasma Concentration (Cmax) of PF-07081532 | 2121 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| Moderate Hepatic Impairment | Maximum Plasma Concentration (Cmax) of PF-07081532 | 2230 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30 |
| Severe Hepatic Impairment | Maximum Plasma Concentration (Cmax) of PF-07081532 | 1536 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [70.86, 127.04]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [74.5, 133.56]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [51.31, 91.98]ANOVA
Primary
Unbound AUCinf (AUCinf,u) of PF-07081532
AUCinf,u is the unbound AUCinf.
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Unbound AUCinf (AUCinf,u) of PF-07081532 | 11.88 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Mild Hepatic Impairment | Unbound AUCinf (AUCinf,u) of PF-07081532 | 11.30 ng*hr/mL | Geometric Coefficient of Variation 91 |
| Moderate Hepatic Impairment | Unbound AUCinf (AUCinf,u) of PF-07081532 | 19.81 ng*hr/mL | Geometric Coefficient of Variation 68 |
| Severe Hepatic Impairment | Unbound AUCinf (AUCinf,u) of PF-07081532 | 28.24 ng*hr/mL | Geometric Coefficient of Variation 65 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [52.6, 172.03]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [92.21, 301.62]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [131.46, 430]ANOVA
Primary
Unbound AUClast (AUClast,u) of PF-07081532
AUClast,u is the unbound AUClast.
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Unbound AUClast (AUClast,u) of PF-07081532 | 11.29 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Mild Hepatic Impairment | Unbound AUClast (AUClast,u) of PF-07081532 | 10.76 ng*hr/mL | Geometric Coefficient of Variation 94 |
| Moderate Hepatic Impairment | Unbound AUClast (AUClast,u) of PF-07081532 | 18.41 ng*hr/mL | Geometric Coefficient of Variation 66 |
| Severe Hepatic Impairment | Unbound AUClast (AUClast,u) of PF-07081532 | 27.02 ng*hr/mL | Geometric Coefficient of Variation 64 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [52.67, 172.59]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [90.1, 295.22]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [132.29, 433.47]ANOVA
Primary
Unbound Cmax (Cmax,u) of PF-07081532
Cmax,u is the unbound Cmax.
Time frame: At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Population: The PK concentration population included all participants who each received 1 dose of PF-07081532 and in whom at least 1 plasma concentration value was reported. The PK parameter analysis population included all participants who each received 1 dose of PF-07081532 and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Unbound Cmax (Cmax,u) of PF-07081532 | 0.6156 ng/mL | Geometric Coefficient of Variation 17 |
| Mild Hepatic Impairment | Unbound Cmax (Cmax,u) of PF-07081532 | 0.5448 ng/mL | Geometric Coefficient of Variation 42 |
| Moderate Hepatic Impairment | Unbound Cmax (Cmax,u) of PF-07081532 | 0.6551 ng/mL | Geometric Coefficient of Variation 36 |
| Severe Hepatic Impairment | Unbound Cmax (Cmax,u) of PF-07081532 | 1.042 ng/mL | Geometric Coefficient of Variation 34 |
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [64.13, 122.12]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [77.11, 146.83]ANOVA
Comparison: One-way ANOVA was used on the natural log transformed PK parameters with hepatic function group as a fixed factor.~The adjusted mean differences and the corresponding 90% confidence intervals derived from ANOVA were exponentiated to provide estimate of the ratio of adjusted geometric means (Test \[hepatic impairment group\]/Reference \[without hepatic impairment group\]) and 90% confidence intervals for the ratio.90% CI: [122.61, 233.47]ANOVA
Secondary
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Safety laboratory assessments included clinical chemistry, hematology, and urinalysis tests. Number of participants with clinical laboratory abnormalities meeting pre-specified criteria is reported.
Time frame: From baseline (BL) to Day 7
Population: The safety analysis set included all participants who each took 1 dose of PF-07081532. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (milligram per deciliter [mg/dL]) >1.5*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin International Normalized Ratio >1.1*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Basophils/Leukocytes (%) >1.2*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen ≥1 | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin Time (sec) >1.1*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (second [sec]) >1.1*ULN | 2 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils/Leukocytes (%) >1.2*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Erythrocytes (10^12/liter [L]) <0.8*LLN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥1 | 1 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ketones ≥1 | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (femtoliter [fL]) >1.1*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hemoglobin (gram per deciliter [g/dL]) <0.8*lower limit of normal (LLN) | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) >1.2*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) <0.8*LLN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (picogram/cell [pg/cell]) <0.9*LLN | 1 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hematocrit (%) <0.8*LLN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Gamma Glutamyl Transferase (U/L) >3.0*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (unit per liter [U/L]) >3.0*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) <0.5*LLN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Epithelial Cells (/low-power field [LPF]) ≥6 | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Indirect Bilirubin (mg/dL) >1.5*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Direct Bilirubin (mg/dL) >1.5*ULN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) <0.8*LLN | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (femtoliter [fL]) >1.1*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hemoglobin (gram per deciliter [g/dL]) <0.8*lower limit of normal (LLN) | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hematocrit (%) <0.8*LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Erythrocytes (10^12/liter [L]) <0.8*LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (picogram/cell [pg/cell]) <0.9*LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) <0.5*LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) <0.8*LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Basophils/Leukocytes (%) >1.2*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils/Leukocytes (%) >1.2*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (second [sec]) >1.1*ULN | 5 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin Time (sec) >1.1*ULN | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin International Normalized Ratio >1.1*ULN | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (milligram per deciliter [mg/dL]) >1.5*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Direct Bilirubin (mg/dL) >1.5*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Indirect Bilirubin (mg/dL) >1.5*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (unit per liter [U/L]) >3.0*ULN | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Gamma Glutamyl Transferase (U/L) >3.0*ULN | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) <0.8*LLN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) >1.2*ULN | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ketones ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥1 | 2 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Epithelial Cells (/low-power field [LPF]) ≥6 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) <0.8*LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (milligram per deciliter [mg/dL]) >1.5*ULN | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hematocrit (%) <0.8*LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Direct Bilirubin (mg/dL) >1.5*ULN | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) <0.5*LLN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Indirect Bilirubin (mg/dL) >1.5*ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (unit per liter [U/L]) >3.0*ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (picogram/cell [pg/cell]) <0.9*LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Gamma Glutamyl Transferase (U/L) >3.0*ULN | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) <0.8*LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (femtoliter [fL]) >1.1*ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Epithelial Cells (/low-power field [LPF]) ≥6 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) >1.2*ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥1 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ketones ≥1 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Erythrocytes (10^12/liter [L]) <0.8*LLN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils/Leukocytes (%) >1.2*ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*ULN | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (second [sec]) >1.1*ULN | 5 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Basophils/Leukocytes (%) >1.2*ULN | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hemoglobin (gram per deciliter [g/dL]) <0.8*lower limit of normal (LLN) | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin Time (sec) >1.1*ULN | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen ≥1 | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin International Normalized Ratio >1.1*ULN | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*ULN | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen ≥1 | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) >1.2*ULN | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (milligram per deciliter [mg/dL]) >1.5*ULN | 4 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) <0.5*LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Erythrocytes (10^12/liter [L]) <0.8*LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Basophils/Leukocytes (%) >1.2*ULN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Direct Bilirubin (mg/dL) >1.5*ULN | 4 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hematocrit (%) <0.8*LLN | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Epithelial Cells (/low-power field [LPF]) ≥6 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ketones ≥1 | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Indirect Bilirubin (mg/dL) >1.5*ULN | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (picogram/cell [pg/cell]) <0.9*LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) <0.8*LLN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥1 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (unit per liter [U/L]) >3.0*ULN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (second [sec]) >1.1*ULN | 5 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils/Leukocytes (%) >1.2*ULN | 2 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Gamma Glutamyl Transferase (U/L) >3.0*ULN | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (femtoliter [fL]) >1.1*ULN | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Hemoglobin (gram per deciliter [g/dL]) <0.8*lower limit of normal (LLN) | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin Time (sec) >1.1*ULN | 6 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) <0.8*LLN | 4 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Prothrombin International Normalized Ratio >1.1*ULN | 6 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
ECG assessments included PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities included PR interval BL \>200msec and max ≥25% increase from BL, or BL ≤200msec and max ≥50% increase from BL, or absolute value ≥300msec; QRS interval percent change from BL ≥50% or absolute value ≥140msec; QTcF change from BL 30- ≤60msec, \>60msec, or absolute value 450- ≤480msec, 480- ≤500msec, or \>500msec.
Time frame: From BL to Day 7
Population: The safety analysis set included all participants who each took 1 dose of PF-07081532.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Value > 500 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 480 < Value ≤ 500 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Change > 60 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval %Change ≥ 50% msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval Value ≥ 140 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval %Change ≥ 25/50% msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 30 < Change ≤ 60 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 450 < Value ≤ 480 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval Value ≥ 300 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 450 < Value ≤ 480 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Value > 500 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 480 < Value ≤ 500 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval %Change ≥ 25/50% msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval Value ≥ 300 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval Value ≥ 140 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Change > 60 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 30 < Change ≤ 60 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval %Change ≥ 50% msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 450 < Value ≤ 480 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval Value ≥ 300 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval %Change ≥ 25/50% msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval Value ≥ 140 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval %Change ≥ 50% msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 480 < Value ≤ 500 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Value > 500 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 30 < Change ≤ 60 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Change > 60 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Value > 500 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval %Change ≥ 50% msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS Interval Value ≥ 140 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF Change > 60 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 30 < Change ≤ 60 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval %Change ≥ 25/50% msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 480 < Value ≤ 500 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF 450 < Value ≤ 480 msec | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR Interval Value ≥ 300 msec | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were defined as events that started during the effective duration of treatment (ie, starting on or after the dose of PF-07081532 up to the final follow-up visit). AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
Time frame: Day 1 to Day 36
Population: The safety analysis set included all participants who each took 1 dose of PF-07081532.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 1 Participants |
| Without Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
Secondary
Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
Vital signs abnormalities included: seated diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg or absolute value \<50mmHg; systolic BP increase and decrease from BL of \>=30mmHg or absolute value \<90mmHg; pulse rate \<40 or \>120bpm.
Time frame: From BL to Day 7
Population: The safety analysis set included all participants who each took 1 dose of PF-07081532.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Increase ≥20mmHg | 1 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Decrease ≥20mmHg | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Value <90mmHg | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value >120bpm | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Decrease ≥30mmHg | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value <40bpm | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Increase ≥30mmHg | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Value <50mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Decrease ≥30mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value >120bpm | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Value <90mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Increase ≥20mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Value <50mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Decrease ≥20mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Increase ≥30mmHg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value <40bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Value <90mmHg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Increase ≥30mmHg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Increase ≥20mmHg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Decrease ≥30mmHg | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Decrease ≥20mmHg | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Value <50mmHg | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value <40bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value >120bpm | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value <40bpm | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Value <50mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Increase ≥20mmHg | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Diastolic BP Decrease ≥20mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Decrease ≥30mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Pulse Rate Value >120bpm | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Value <90mmHg | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Systolic BP Increase ≥30mmHg | 0 Participants |