Healthy Volunteers, Hepatic Impairment
Conditions
Brief summary
The current study is proposed to evaluate whether there is any clinically meaningful effect of hepatic impairment on the plasma Pharmacokinetic (PK) of PF-06882961
Interventions
DRUGPF-06882961 20MG
PF-06882961 in 20 mg oral tablet will be administered on Day 1
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants between the ages of 18 (or the minimum country-specific age of consent if \>18) and 70 years, inclusive, at the screening visit: * Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. * Body mass index (BMI) of 17.5 to 38.0 kg/m2, inclusive; and a total body weight \>50 kg (110 lb), at the screening visit; with a single repeat assessment of total body weight (and hence BMI), on a separate day permitted to assess eligibility, if needed.
Exclusion criteria
* Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection); NOTE: Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study as long as the surgery occurred more than 6 months prior to Screening; * At screening, participants with a positive result for human immunodeficiency virus (HIV) antibodies, as assessed by sponsor-identified central laboratory, with a single repeat permitted to assess eligibility, if needed; * A positive COVID-19 test at screening; * A diagnosis of type 2 diabetes mellitus (T2DM) that is documented by medical history; * Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or participants with suspected MTC per the investigator's judgement; * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study; * Use of prior/concomitant therapies * Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer); * Participants with known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF-06882961; * Participants with ANY of the following abnormalities in clinical laboratory tests at Visit 1, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary: HbA1c ≥6.5%; FPG ≥126 mg/Dl; eGFR\<60 mL/min/1.73m2; * A positive urine drug test, for illicit drugs at screening, as assessed by sponsor-identified central laboratory. However, participants in Cohorts 2-4, only, who have been medically prescribed opiates/opioids or benzodiazepines and report the use of these drugs to the investigator at the Screening visit will be allowed to participate; NOTE: repeat urine drug testing is not permitted in this study; * At screening or Day -1, a positive breath alcohol test, as assessed using kits provided by sponsor-identified central laboratory, with a single repeat on a separate day permitted to assess eligibility, if needed; * Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing and until the follow-up contact; 13. History of sensitivity to heparin or heparin-induced thrombocytopenia, only if heparin is used to flush intravenous catheters used during serial blood collections; * Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol; * Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Unbound Drug in Plasma (fu) | Predose (0 hours), and 4 hours post dose on Day 1. | fu = Cu/C (where Cu represents unbound concentration and C represents total concentration). |
| Maximum Plasma Concentration (Cmax) | Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1. | Maximum observed plasma PF-06882961 concentration. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) | Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1. | Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to infinite time. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1. | Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to the time of the last quantifiable concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | Baseline to Day 30 | Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. AEs included SAEs and non-serious AEs. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Relatedness to study treatment was determined by the investigator. |
| Number of Participants With Clinical Laboratory Abnormalities | Baseline to Day 3 | Protocol-required safety laboratory assessments included: hemoglobin \<0.8 x lower limit of normal (LLN), hematocrit \<0.8 x LLN, erythrocytes \<0.8 x LLN, ery. mean corpuscular volume \>1.1 x upper limit of normal (ULN), ery. mean corpuscular hemoglobin \>1.1 x ULN, platelets \<0.5 x LLN, eosinophils \>1.2 x ULN, activated partial thromboplastin time \>1.1 x ULN, prothrombin time \>1.1 x ULN, prothrombin intl. normalized ratio \>1.1 x ULN; bilirubin/direct bilirubin/indirect bilirubin \>1.5 x ULN, aspartate aminotransferase/alanine aminotransferase/gamma glutamyl transferase \>3.0 x ULN, albumin \<0.8 x LLN, urate \>1.2 x ULN, bicarbonate \>1.1 x ULN, triacylglycerol lipase \>1.5 x ULN; urine hemoglobin/urine urobilinogen/urine nitrite/urine leukocyte esterase ≥1. |
| Number of Participants With Categorical Vital Signs Data | Baseline to Day 3 | Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (≥) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP ≥ 20 mmHg. |
| Number of Participants With Categorical Electrocardiogram (ECG) Data | Baseline to Day 3 | ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (≥) 300 millisecond (msec), b) ≥25% increase when baseline is \> 200 msec or ≥50% increase when baseline is less than or equal to (≤) 200 msec. 2\. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) ≥140 msec, b) ≥50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and ≤480 msec, b) \>480 msec and ≤500 msec, c) \>500 msec, d) \>30 msec and ≤60 msec increase from baseline, e) \>60 msec increase from baseline |
Countries
United States
Participant flow
Pre-assignment details
A total of 29 participants were screened in the study, among whom, 24 participants were treated with PF-06882961 (Danuglipron).
Participants by arm
| Arm | Count |
|---|---|
| Without Hepatic Impairment Participants without hepatic impairment received a single, oral dose of PF-06882961 20 mg in the fed state on Day 1. | 6 |
| Mild Hepatic Impairment Participants with mild hepatic impairment received a single, oral dose of PF-06882961 20 mg in the fed state on Day 1. | 6 |
| Moderate Hepatic Impairment Participants with moderate hepatic impairment received a single, oral dose of PF-06882961 20 mg in the fed state on Day 1. | 6 |
| Severe Hepatic Impairment Participants with severe hepatic impairment received a single, oral dose of PF-06882961 20 mg in the fed state on Day 1. | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Without Hepatic Impairment | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59.3 Years STANDARD_DEVIATION 3.08 | 61.7 Years STANDARD_DEVIATION 5.85 | 57.7 Years STANDARD_DEVIATION 7.12 | 56.2 Years STANDARD_DEVIATION 10.21 | 58.7 Years STANDARD_DEVIATION 6.89 |
| Age, Customized 45-64 Years | 6 Participants | 3 Participants | 5 Participants | 4 Participants | 18 Participants |
| Age, Customized >=65 Years | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 13 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 | 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)
Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Population: The analysis population refers to all participants who received at least 1 dose of PF-06882961 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) | 193.4 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 83 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) | 237.3 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) | 546.7 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 116 |
| Severe Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) | 1239 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 75 |
Comparison: Test: the mild hepatic impairment group; Reference: the without hepatic impairment group90% CI: [61.33, 245.49]
Comparison: Test: the moderate hepatic impairment Group; Reference: the without hepatic impairment group90% CI: [141.32, 565.66]
Comparison: Test: the severe hepatic impairment group; Reference: the without hepatic impairment group90% CI: [320.27, 1282]
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to the time of the last quantifiable concentration.
Time frame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Population: The analysis population refers to all participants who received at least 1 dose of PF-06882961 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) | 191.2 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 84 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | 235.0 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | 542.9 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 117 |
| Severe Hepatic Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | 1217 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 73 |
Comparison: Test: the mild hepatic impairment group; Reference: the without hepatic impairment group90% CI: [61.51, 245.51]
Comparison: Test: the moderate hepatic impairment Group; Reference: the without hepatic impairment group90% CI: [142.1, 567.13]
Comparison: Test: the severe hepatic impairment group; Reference: the without hepatic impairment group90% CI: [318.51, 1271.24]
Primary
Fraction of Unbound Drug in Plasma (fu)
fu = Cu/C (where Cu represents unbound concentration and C represents total concentration).
Time frame: Predose (0 hours), and 4 hours post dose on Day 1.
Population: The analysis population refers to all participants who received at least 1 dose of PF-06882961 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) | 0.02137 Ratio | Geometric Coefficient of Variation 18 |
| Mild Hepatic Impairment | Fraction of Unbound Drug in Plasma (fu) | 0.01820 Ratio | Geometric Coefficient of Variation 13 |
| Moderate Hepatic Impairment | Fraction of Unbound Drug in Plasma (fu) | 0.02059 Ratio | Geometric Coefficient of Variation 21 |
| Severe Hepatic Impairment | Fraction of Unbound Drug in Plasma (fu) | 0.02889 Ratio | Geometric Coefficient of Variation 53 |
Comparison: Test: the mild hepatic impairment group; Reference: the without hepatic impairment group90% CI: [63.6, 114.1]
Comparison: Test: the moderate hepatic impairment Group; Reference: the without hepatic impairment group90% CI: [71.95, 129.07]
Comparison: Test: the severe hepatic impairment group; Reference: the without hepatic impairment group90% CI: [100.94, 181.1]
Primary
Maximum Plasma Concentration (Cmax)
Maximum observed plasma PF-06882961 concentration.
Time frame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Population: The analysis population refers to all participants who received at least 1 dose of PF-06882961 and had at least 1 of the pharmacokinetic (PK) parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Without Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 23.56 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| Mild Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 31.37 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| Moderate Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 51.82 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 83 |
| Severe Hepatic Impairment | Maximum Plasma Concentration (Cmax) | 78.73 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
Comparison: Test: the mild hepatic impairment group; Reference: the without hepatic impairment group90% CI: [81.97, 216.37]
Comparison: Test: the moderate hepatic impairment Group; Reference: the without hepatic impairment group90% CI: [135.39, 357.41]
Comparison: Test: the severe hepatic impairment group; Reference: the without hepatic impairment group90% CI: [205.7, 543]
Secondary
Number of Participants Reporting Treatment-emergent Adverse Events (AEs)
Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. AEs included SAEs and non-serious AEs. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Relatedness to study treatment was determined by the investigator.
Time frame: Baseline to Day 30
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | All-causality | 0 Participants |
| Without Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | Treatment-related | 0 Participants |
| Mild Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | Treatment-related | 1 Participants |
| Mild Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | All-causality | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | All-causality | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | Treatment-related | 2 Participants |
| Severe Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | All-causality | 1 Participants |
| Severe Hepatic Impairment | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | Treatment-related | 1 Participants |
Secondary
Number of Participants With Categorical Electrocardiogram (ECG) Data
ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (≥) 300 millisecond (msec), b) ≥25% increase when baseline is \> 200 msec or ≥50% increase when baseline is less than or equal to (≤) 200 msec. 2\. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) ≥140 msec, b) ≥50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and ≤480 msec, b) \>480 msec and ≤500 msec, c) \>500 msec, d) \>30 msec and ≤60 msec increase from baseline, e) \>60 msec increase from baseline
Time frame: Baseline to Day 3
Population: All participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >500 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >480 and ≤500 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >60 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in QRS interval ≥50% | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QRS interval ≥140 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in PR interval ≥25/50% | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >450 and ≤480 msec | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | PR interval ≥300 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >450 and ≤480 msec | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >500 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >480 and ≤500 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in PR interval ≥25/50% | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | PR interval ≥300 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QRS interval ≥140 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >60 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in QRS interval ≥50% | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >450 and ≤480 msec | 1 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | PR interval ≥300 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in PR interval ≥25/50% | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QRS interval ≥140 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in QRS interval ≥50% | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >480 and ≤500 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >500 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >60 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >500 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in QRS interval ≥50% | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QRS interval ≥140 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >60 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | %Change in PR interval ≥25/50% | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >480 and ≤500 msec | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | QTcF interval >450 and ≤480 msec | 3 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Electrocardiogram (ECG) Data | PR interval ≥300 msec | 0 Participants |
Secondary
Number of Participants With Categorical Vital Signs Data
Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (≥) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP ≥ 20 mmHg.
Time frame: Baseline to Day 3
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value <40 bpm | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg decrease | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg decrease | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value >120 bpm | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP value <90 mm Hg | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP value <50 mm Hg | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg increase | 0 Participants |
| Without Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg increase | 1 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value <40 bpm | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg increase | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg decrease | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP value <50 mm Hg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg increase | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg decrease | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP value <90 mm Hg | 0 Participants |
| Mild Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value >120 bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP value <90 mm Hg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg increase | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value >120 bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg decrease | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP value <50 mm Hg | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value <40 bpm | 0 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg increase | 2 Participants |
| Moderate Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg decrease | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg decrease | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value <40 bpm | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Pulse rate value >120 bpm | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP value <50 mm Hg | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg increase | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting DBP Change ≥ 20 mm Hg decrease | 0 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP value <90 mm Hg | 1 Participants |
| Severe Hepatic Impairment | Number of Participants With Categorical Vital Signs Data | Sitting SBP Change ≥ 30 mm Hg increase | 0 Participants |
Secondary
Number of Participants With Clinical Laboratory Abnormalities
Protocol-required safety laboratory assessments included: hemoglobin \<0.8 x lower limit of normal (LLN), hematocrit \<0.8 x LLN, erythrocytes \<0.8 x LLN, ery. mean corpuscular volume \>1.1 x upper limit of normal (ULN), ery. mean corpuscular hemoglobin \>1.1 x ULN, platelets \<0.5 x LLN, eosinophils \>1.2 x ULN, activated partial thromboplastin time \>1.1 x ULN, prothrombin time \>1.1 x ULN, prothrombin intl. normalized ratio \>1.1 x ULN; bilirubin/direct bilirubin/indirect bilirubin \>1.5 x ULN, aspartate aminotransferase/alanine aminotransferase/gamma glutamyl transferase \>3.0 x ULN, albumin \<0.8 x LLN, urate \>1.2 x ULN, bicarbonate \>1.1 x ULN, triacylglycerol lipase \>1.5 x ULN; urine hemoglobin/urine urobilinogen/urine nitrite/urine leukocyte esterase ≥1.
Time frame: Baseline to Day 3
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Without Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities | 3 Participants |
| Mild Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities | 4 Participants |
| Moderate Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities | 5 Participants |
| Severe Hepatic Impairment | Number of Participants With Clinical Laboratory Abnormalities | 6 Participants |