Hepatic Impairment
Conditions
Brief summary
Hepatic impairment PK study
Detailed description
This is a non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (total and unbound) of PF-05221304 after a single oral dose administered in the fed state.
Interventions
DRUGPF-05221304
25 mg dose
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
Key
Exclusion criteria
All subjects - * Adults \<18 years of age and \>70 years of age * BMI \< 17.5 and \> 35.4 kg/m2 * HIV positive * Conditions that affect drug absorption * Positive breath alcohol test Healthy/ those without hepatic impairment - * Known or suspected hepatic impairment * Evidence of Hepatitis B or C * On any chronic medications Those with varying degrees of hepatic impairment - * Not meeting Classification A, B, or C of hepatic impairment based on Child-Pugh Classification * Evidence of Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy * Recent GI bleed * Moderate or severe renal impairment * Hepatic encephalopathy Grade 3 or higher
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unbound Cmax (Cmax,u) of PF-05221304 | 4 hours postdose | Cmax,u was calculated by fu\*Cmax. |
| Unbound AUCinf (AUCinf,u) of PF-05221304 | 4 hours postdose | AUCinf,u was calculated by fu\*AUCinf. |
| Maximum Plasma Concentration (Cmax) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | Cmax was observed directly from data. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | AUCinf was calculated by AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Fraction Unbound (fu) of PF-05221304 | 4 hours postdose | fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | Vz/F was calculated by Dose/(AUCinf\*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Unbound Vz/F (Vz,u/F) of PF-05221304 | 4 hours postdose | Vz,u/F was calculated by fu\*Vz/F. |
| Terminal Half-Life ( t½) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | t1/2 was calculated by loge(2)/kel. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Approximately 30 days | An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below. |
| Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | Tmax was observed directly from data as time of first occurrence. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | 7 days | Clinical chemistry evaluation included: bilirubin, direct/indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase , alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, phosphate, bicarbonate, creatine kinase, and fasting glucose. |
| Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | 7 days | Urinalysis evaluation included: scalar urine glucose, scalar ketones, scalar urine protein, scalar urine hemoglobin, scalar urobilinogen, scalar urine bilirubin, scalar nitrite, scalar leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and scalar bacteria. |
| Number of Participants With Clinical Significant Findings in Vital Signs | 7 days | Vital signs evaluation included: sitting systolic and diastolic blood pressure (BP), and sitting pulse rate. Clinically significant findings in vital signs were determined by the investigator. |
| Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 7 days | ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and heart rate. Clinically significant findings in ECG data were determined by the investigator. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | 7 days | Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, reticulocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration (MCHC), erythrocyte mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time and prothrombin time. |
| Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | AUClast was calculated by linear/Log trapezoidal method. |
| Unbound AUClast ( AUClast,u) of PF-05221304 | 4 hours postdose | AUClast,u was calculated by fu\*AUClast. |
| Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose | CL/F was calculated by Dose/AUCinf. |
| Unbound CL/F (CLu/F) of PF-05221304 | 4 hours postdose | CLu/F was calculated by fu\*CL/F. |
Countries
Belgium, Czechia, Slovakia, United States
Participant flow
Recruitment details
Recruitment for participants in Cohorts 3 and 4 initiated first and recruitment for participants in Cohort 2 started when approximately 50% of total participants across Cohorts 3 and 4 had been dosed. Participants in Cohort 1 were recruited last to match the average demographics across the pooled Cohorts 2 through 4.
Pre-assignment details
A total of 24 subjects with 4 varying degrees of hepatic function were enrolled into the study to ensure that up to 6 evaluable subjects in each of the 4 hepatic function cohorts complete the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Without Hepatic Impairment) Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7. | 6 |
| Cohort 2 (Mild Hepatic Impairment) Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7. | 6 |
| Cohort 3 (Moderate Hepatic Impairment) Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7. | 6 |
| Cohort 4 (Severe Hepatic Impairment) Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 21 Participants |
| Age, Continuous | 56.17 Years STANDARD_DEVIATION 2.23 | 55.50 Years STANDARD_DEVIATION 9.73 | 60.00 Years STANDARD_DEVIATION 5.97 | 55.33 Years STANDARD_DEVIATION 7.5 | 56.75 Years STANDARD_DEVIATION 6.74 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 5 Participants | 6 Participants | 6 Participants | 21 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 5 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 | 0 / 6 | 1 / 6 | 2 / 6 | 0 / 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-05221304
AUCinf was calculated by AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 17520 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36 |
| Cohort 2 (Mild Hepatic Impairment) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 23890 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| Cohort 3 (Moderate Hepatic Impairment) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 21770 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Cohort 4 (Severe Hepatic Impairment) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 20790 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
90% CI: [94.63, 196.53]ANOVA
90% CI: [86.2, 179.03]ANOVA
90% CI: [82.33, 170.99]ANOVA
Primary
Fraction Unbound (fu) of PF-05221304
fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Time frame: 4 hours postdose
Population: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Fraction Unbound (fu) of PF-05221304 | 0.005519 Ratio | Geometric Coefficient of Variation 44 |
| Cohort 2 (Mild Hepatic Impairment) | Fraction Unbound (fu) of PF-05221304 | 0.006883 Ratio | Geometric Coefficient of Variation 55 |
| Cohort 3 (Moderate Hepatic Impairment) | Fraction Unbound (fu) of PF-05221304 | 0.008117 Ratio | Geometric Coefficient of Variation 45 |
| Cohort 4 (Severe Hepatic Impairment) | Fraction Unbound (fu) of PF-05221304 | 0.01240 Ratio | Geometric Coefficient of Variation 26 |
90% CI: [82.5275, 188.5165]ANOVA
90% CI: [97.3132, 222.2911]ANOVA
90% CI: [148.6962, 339.6647]ANOVA
Primary
Maximum Plasma Concentration (Cmax) of PF-05221304
Cmax was observed directly from data.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Maximum Plasma Concentration (Cmax) of PF-05221304 | 1220 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| Cohort 2 (Mild Hepatic Impairment) | Maximum Plasma Concentration (Cmax) of PF-05221304 | 1591 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| Cohort 3 (Moderate Hepatic Impairment) | Maximum Plasma Concentration (Cmax) of PF-05221304 | 1433 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| Cohort 4 (Severe Hepatic Impairment) | Maximum Plasma Concentration (Cmax) of PF-05221304 | 1592 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
90% CI: [101.57, 167.6]ANOVA
90% CI: [91.46, 150.93]ANOVA
90% CI: [101.63, 167.7]ANOVA
Primary
Unbound AUCinf (AUCinf,u) of PF-05221304
AUCinf,u was calculated by fu\*AUCinf.
Time frame: 4 hours postdose
Population: The analysis population was defined as all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Unbound AUCinf (AUCinf,u) of PF-05221304 | 96.78 ng*hr/mL | Geometric Coefficient of Variation 75 |
| Cohort 2 (Mild Hepatic Impairment) | Unbound AUCinf (AUCinf,u) of PF-05221304 | 164.4 ng*hr/mL | Geometric Coefficient of Variation 34 |
| Cohort 3 (Moderate Hepatic Impairment) | Unbound AUCinf (AUCinf,u) of PF-05221304 | 176.6 ng*hr/mL | Geometric Coefficient of Variation 51 |
| Cohort 4 (Severe Hepatic Impairment) | Unbound AUCinf (AUCinf,u) of PF-05221304 | 257.7 ng*hr/mL | Geometric Coefficient of Variation 45 |
90% CI: [104.02, 277.32]ANOVA
90% CI: [111.78, 298.02]ANOVA
90% CI: [163.08, 434.8]ANOVA
Primary
Unbound Cmax (Cmax,u) of PF-05221304
Cmax,u was calculated by fu\*Cmax.
Time frame: 4 hours postdose
Population: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Unbound Cmax (Cmax,u) of PF-05221304 | 6.731 ng/mL | Geometric Coefficient of Variation 57 |
| Cohort 2 (Mild Hepatic Impairment) | Unbound Cmax (Cmax,u) of PF-05221304 | 10.94 ng/mL | Geometric Coefficient of Variation 44 |
| Cohort 3 (Moderate Hepatic Impairment) | Unbound Cmax (Cmax,u) of PF-05221304 | 11.63 ng/mL | Geometric Coefficient of Variation 48 |
| Cohort 4 (Severe Hepatic Impairment) | Unbound Cmax (Cmax,u) of PF-05221304 | 19.74 ng/mL | Geometric Coefficient of Variation 43 |
90% CI: [103.12, 256.32]ANOVA
90% CI: [109.56, 272.35]ANOVA
90% CI: [186.04, 462.44]ANOVA
Secondary
Apparent Clearance After Oral Dose (CL/F) of PF-05221304
CL/F was calculated by Dose/AUCinf.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | 1.427 Liter per hour (L/hr) | Geometric Coefficient of Variation 36 |
| Cohort 2 (Mild Hepatic Impairment) | Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | 1.048 Liter per hour (L/hr) | Geometric Coefficient of Variation 41 |
| Cohort 3 (Moderate Hepatic Impairment) | Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | 1.151 Liter per hour (L/hr) | Geometric Coefficient of Variation 31 |
| Cohort 4 (Severe Hepatic Impairment) | Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | 1.202 Liter per hour (L/hr) | Geometric Coefficient of Variation 43 |
Secondary
Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304
Vz/F was calculated by Dose/(AUCinf\*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 34.94 Liters | Geometric Coefficient of Variation 35 |
| Cohort 2 (Mild Hepatic Impairment) | Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 24.53 Liters | Geometric Coefficient of Variation 24 |
| Cohort 3 (Moderate Hepatic Impairment) | Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 23.16 Liters | Geometric Coefficient of Variation 28 |
| Cohort 4 (Severe Hepatic Impairment) | Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 23.97 Liters | Geometric Coefficient of Variation 23 |
Secondary
Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304
AUClast was calculated by linear/Log trapezoidal method.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 | 17400 ng*hr/mL | Geometric Coefficient of Variation 36 |
| Cohort 2 (Mild Hepatic Impairment) | Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 | 23670 ng*hr/mL | Geometric Coefficient of Variation 40 |
| Cohort 3 (Moderate Hepatic Impairment) | Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 | 21680 ng*hr/mL | Geometric Coefficient of Variation 31 |
| Cohort 4 (Severe Hepatic Impairment) | Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 | 20700 ng*hr/mL | Geometric Coefficient of Variation 43 |
Secondary
Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data
ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and heart rate. Clinically significant findings in ECG data were determined by the investigator.
Time frame: 7 days
Population: The analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 0 Participants |
Secondary
Number of Participants With Clinical Significant Findings in Vital Signs
Vital signs evaluation included: sitting systolic and diastolic blood pressure (BP), and sitting pulse rate. Clinically significant findings in vital signs were determined by the investigator.
Time frame: 7 days
Population: The analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Clinical Significant Findings in Vital Signs | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Clinical Significant Findings in Vital Signs | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Clinical Significant Findings in Vital Signs | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Clinical Significant Findings in Vital Signs | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Clinical chemistry evaluation included: bilirubin, direct/indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase , alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, phosphate, bicarbonate, creatine kinase, and fasting glucose.
Time frame: 7 days
Population: The analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alkaline Phosphatase >3.0*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Gamma Glutamyl Transferase >3.0*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alanine Aminotransferase >3.0*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bilirubin >1.5*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Aspartate Aminotransferase >3.0*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Indirect Bilirubin >1.5*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium >1.05*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium <0.95*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting Glucose <0.6*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatinine >1.3*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Blood Urea Nitrogen >1.3*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatine Kinase >2.0*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Urate >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting-Glucose >1.5*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting-Glucose >1.5*ULN | 1 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin <0.8*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate <0.8*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bilirubin >1.5*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Direct Bilirubin >1.5*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Indirect Bilirubin >1.5*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Aspartate Aminotransferase >3.0*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alanine Aminotransferase >3.0*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Gamma Glutamyl Transferase >3.0*ULN | 1 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alkaline Phosphatase >3.0*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein <0.8*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Blood Urea Nitrogen >1.3*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatinine >1.3*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Urate >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium <0.95*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium >1.05*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatine Kinase >2.0*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting Glucose <0.6*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin <0.8*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Blood Urea Nitrogen >1.3*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting Glucose <0.6*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate <0.8*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Urate >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatinine >1.3*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium <0.95*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Indirect Bilirubin >1.5*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bilirubin >1.5*ULN | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatine Kinase >2.0*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Aspartate Aminotransferase >3.0*ULN | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alanine Aminotransferase >3.0*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting-Glucose >1.5*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Gamma Glutamyl Transferase >3.0*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Direct Bilirubin >1.5*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein <0.8*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alkaline Phosphatase >3.0*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium >1.05*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatine Kinase >2.0*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein <0.8*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Protein >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin <0.8*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Albumin >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Phosphate <0.8*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Blood Urea Nitrogen >1.3*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium >1.05*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bicarbonate >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Creatinine >1.3*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Potassium >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Chloride <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Sodium <0.95*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting Glucose <0.6*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Direct Bilirubin >1.5*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Bilirubin >1.5*ULN | 5 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Indirect Bilirubin >1.5*ULN | 2 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Aspartate Aminotransferase >3.0*ULN | 2 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Fasting-Glucose >1.5*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alanine Aminotransferase >3.0*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Calcium <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Gamma Glutamyl Transferase >3.0*ULN | 2 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Urate >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | Alkaline Phosphatase >3.0*ULN | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, reticulocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration (MCHC), erythrocyte mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time and prothrombin time.
Time frame: 7 days
Population: The analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes <0.5*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets >1.75*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes >1.5*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Activated Partial Thromboplastin Time >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocytes <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes >1.5*upper limit of normal (ULN) | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC >1.1*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets <0.5*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes <0.6*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils <0.8*LLN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Basophils >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Eosinophils >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Monocytes >1.2*ULN | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Prothrombin Time >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes >1.5*upper limit of normal (ULN) | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes >1.5*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Eosinophils >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Monocytes >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes <0.6*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets <0.5*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Prothrombin Time >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Basophils >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes >1.2*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC <0.9*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils <0.8*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes <0.8*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Activated Partial Thromboplastin Time >1.1*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocytes <0.8*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets >1.75*ULN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes <0.5*LLN | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils <0.8*LLN | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Basophils >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Monocytes >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Prothrombin Time >1.1*ULN | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Activated Partial Thromboplastin Time >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocytes <0.8*LLN | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets >1.75*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Eosinophils >1.2*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes <0.6*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes >1.5*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes <0.5*LLN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes >1.5*upper limit of normal (ULN) | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC >1.1*ULN | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes <0.8*LLN | 2 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets <0.5*LLN | 3 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Monocytes >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes <0.6*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hematocrit <0.8*LLN | 1 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Leukocytes >1.5*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocytes <0.8*LLN | 1 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets <0.5*LLN | 2 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes <0.5*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes <0.8*LLN | 1 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Eosinophils >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 1 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Neutrophils <0.8*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Activated Partial Thromboplastin Time >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Volume <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Basophils >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Prothrombin Time >1.1*ULN | 3 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte MCHC >1.1*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Platelets >1.75*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Lymphocytes >1.2*ULN | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | Reticulocytes >1.5*upper limit of normal (ULN) | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.
Time frame: Approximately 30 days
Population: The analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality TEAE | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality TEAE | 1 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality TEAE | 2 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality TEAE | 0 Participants |
Secondary
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Urinalysis evaluation included: scalar urine glucose, scalar ketones, scalar urine protein, scalar urine hemoglobin, scalar urobilinogen, scalar urine bilirubin, scalar nitrite, scalar leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and scalar bacteria.
Time frame: 7 days
Population: The analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urobilinogen >=1 | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Glucose >=1 | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Bacteria >20 | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Hemoglobin >=1 | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Ketones >=1 | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Leukocytes >=20 (/HPF) | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Erythrocytes >=20 (/high power field [HPF]) | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Leukocyte Esterase >=1 | 1 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Nitrite >=1 | 1 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Protein >=1 | 0 Participants |
| Cohort 1 (Without Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Bilirubin >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Bacteria >20 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Protein >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urobilinogen >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Hyaline Casts >1 (/low power field [LPF]) | 1 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Glucose >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Ketones >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Hemoglobin >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Bilirubin >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Nitrite >=1 | 0 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Leukocyte Esterase >=1 | 1 Participants |
| Cohort 2 (Mild Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Leukocytes >=20 (/HPF) | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Glucose >=1 | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Hemoglobin >=1 | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urobilinogen >=1 | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Bacteria >20 | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Leukocytes >=20 (/HPF) | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Hyaline Casts >1 (/low power field [LPF]) | 1 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Nitrite >=1 | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Erythrocytes >=20 (/high power field [HPF]) | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Bilirubin >=1 | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Leukocyte Esterase >=1 | 2 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Ketones >=1 | 0 Participants |
| Cohort 3 (Moderate Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Protein >=1 | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Nitrite >=1 | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Hemoglobin >=1 | 1 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Bacteria >20 | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Ketones >=1 | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urobilinogen >=1 | 3 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Protein >=1 | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Leukocyte Esterase >=1 | 1 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Bilirubin >=1 | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Leukocytes >=20 (/HPF) | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Urine Erythrocytes >=20 (/high power field [HPF]) | 0 Participants |
| Cohort 4 (Severe Hepatic Impairment) | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | Scalar Urine Glucose >=1 | 0 Participants |
Secondary
Terminal Half-Life ( t½) of PF-05221304
t1/2 was calculated by loge(2)/kel.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Terminal Half-Life ( t½) of PF-05221304 | 17.43 Hours | Standard Deviation 4.7471 |
| Cohort 2 (Mild Hepatic Impairment) | Terminal Half-Life ( t½) of PF-05221304 | 17.25 Hours | Standard Deviation 6.8372 |
| Cohort 3 (Moderate Hepatic Impairment) | Terminal Half-Life ( t½) of PF-05221304 | 14.30 Hours | Standard Deviation 3.4135 |
| Cohort 4 (Severe Hepatic Impairment) | Terminal Half-Life ( t½) of PF-05221304 | 14.76 Hours | Standard Deviation 5.7937 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304
Tmax was observed directly from data as time of first occurrence.
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Population: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | 4.01 Hours |
| Cohort 2 (Mild Hepatic Impairment) | Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | 4.95 Hours |
| Cohort 3 (Moderate Hepatic Impairment) | Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | 4.50 Hours |
| Cohort 4 (Severe Hepatic Impairment) | Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | 4.00 Hours |
Secondary
Unbound AUClast ( AUClast,u) of PF-05221304
AUClast,u was calculated by fu\*AUClast.
Time frame: 4 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Unbound AUClast ( AUClast,u) of PF-05221304 | 96.07 ng*hr/mL | Geometric Coefficient of Variation 75 |
| Cohort 2 (Mild Hepatic Impairment) | Unbound AUClast ( AUClast,u) of PF-05221304 | 163.3 ng*hr/mL | Geometric Coefficient of Variation 34 |
| Cohort 3 (Moderate Hepatic Impairment) | Unbound AUClast ( AUClast,u) of PF-05221304 | 175.9 ng*hr/mL | Geometric Coefficient of Variation 51 |
| Cohort 4 (Severe Hepatic Impairment) | Unbound AUClast ( AUClast,u) of PF-05221304 | 256.7 ng*hr/mL | Geometric Coefficient of Variation 45 |
Secondary
Unbound CL/F (CLu/F) of PF-05221304
CLu/F was calculated by fu\*CL/F.
Time frame: 4 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Unbound CL/F (CLu/F) of PF-05221304 | 258.7 L/hr | Geometric Coefficient of Variation 75 |
| Cohort 2 (Mild Hepatic Impairment) | Unbound CL/F (CLu/F) of PF-05221304 | 152.0 L/hr | Geometric Coefficient of Variation 33 |
| Cohort 3 (Moderate Hepatic Impairment) | Unbound CL/F (CLu/F) of PF-05221304 | 141.6 L/hr | Geometric Coefficient of Variation 51 |
| Cohort 4 (Severe Hepatic Impairment) | Unbound CL/F (CLu/F) of PF-05221304 | 97.02 L/hr | Geometric Coefficient of Variation 45 |
Secondary
Unbound Vz/F (Vz,u/F) of PF-05221304
Vz,u/F was calculated by fu\*Vz/F.
Time frame: 4 hours postdose
Population: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Without Hepatic Impairment) | Unbound Vz/F (Vz,u/F) of PF-05221304 | 6334 Liters | Geometric Coefficient of Variation 69 |
| Cohort 2 (Mild Hepatic Impairment) | Unbound Vz/F (Vz,u/F) of PF-05221304 | 3563 Liters | Geometric Coefficient of Variation 51 |
| Cohort 3 (Moderate Hepatic Impairment) | Unbound Vz/F (Vz,u/F) of PF-05221304 | 2854 Liters | Geometric Coefficient of Variation 59 |
| Cohort 4 (Severe Hepatic Impairment) | Unbound Vz/F (Vz,u/F) of PF-05221304 | 1931 Liters | Geometric Coefficient of Variation 37 |