Healthy, Hepatic Impairment
Conditions
Brief summary
The purpose of this study is to understand the effects of decreased liver function on the study medicine (PF-07328948). People with decreased liver function may process the study medicine differently from healthy people. Study is seeking participants who: * Are between 18 and 75 years of age. * Have a BMI (body mass index) of 17.5 to 40 kg/m2, inclusive, and a total body weight of more than or equal to 45 kilograms or 99 pounds. Participants will take the study medicine as a tablet once at the study clinic and then will stay onsite for about 6 days. During this time, the study team will check for the participant's treatment experience and take some blood samples to test the level of PF-07328948. This will help understand if certain level of decreased liver function could affect the study medicine being processed in the body.
Interventions
DRUGPF-07328948
PF-07328948, 1 tablet orally, once on Day 1
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female of nonchildbearing potential, between the ages of 18 (inclusive) and 75 years, at the screening visit. * Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. * BMI of 17.5 to 40.0 kg/m2 (inclusive), and a total body weight ≥45 kg (99 lb). * Group 4 only: at screening, no clinically relevant abnormalities identified by a detailed medical history, physical exam, including blood pressure and pulse rate measurement, ECG and clinical laboratory tests. * Group 4 only: no known or suspected hepatic impairment and meet the criteria based on screening laboratory liver function tests. * Groups 1, 2 \& 3 only: stable hepatic impairment that meets criteria for Class A, B, or C of the Child-Pugh classification with no clinically significant change in disease status within 28 days before screening. * Groups 1, 2 \& 3 only: stable concomitant medications for the management of individual participant's medical history.
Exclusion criteria
* Any condition possibly affecting drug absorption * At screening, a positive result for HIV antibodies. * Evidence of a prothrombotic state, including history of deep vein thrombosis, pulmonary embolism, or arterial thrombosis, or known genetic predisposition. * Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study. * Use of specific prohibited prior/concomitant therapies * Use of an investigational product within 30 days or 5 half-lives (whichever longer). * eGFR\<60 mL/min/1.73m2 at screening. * A positive urine drug test at screening or admission to study clinic. * At screening or admission to study clinic, a positive breath alcohol test. * History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of screening. * Group 4 only: evidence of chronic liver disease including history of hepatitis, hepatitis B, or hepatitis C. * Group 4 only: screening ECG demonstrating QTcF interval \>450 ms or a QRS interval \>120 ms. * Group 4 only: screening seated systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg * Group 1, 2 \& 3 only: Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as \<1 year in Groups 2 \& 3 and \<6 months for Group 1 only). * Group 1, 2 \& 3 only: a diagnosis of hepatic dysfunction secondary to any acute ongoing hepatocellular process that is documented by medical history, physical exam, liver biopsy, hepatic ultrasound, CT scan, or MRI. * Group 1, 2 \& 3 only: history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 4 weeks prior to screening. * Group 1, 2 \& 3 only: signs of clinically active Grade 3 or 4 hepatic encephalopathy * Groups 1, 2 \& 3 only: severe ascites and/or pleural effusion, except for those categorized in Group 4 who may be enrolled provided participant is medically stable, per the study doctor's judgment. * Groups 1, 2 \& 3 only: previously received a kidney, liver, or heart transplant. * Groups 1, 2, \& 3 only: screening ECG demonstrating a QTcF interval \>470 ms or a QRS interval \>120 ms. * Groups 1, 2 \& 3 only: persistent severe, uncontrolled hypertension at screening, admission to study clinic, or pre-dose on Day 1. * Groups 1, 2 \& 3 only: ALT or AST \>5x upper limit of normal on clinical laboratory tests at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Unbound Drug in Plasma (Fu) of PF-07328948 | At 0 (prior to dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post dose on Day 1 | Fu is the fraction of unbound drug in plasma, which is calculated by Cu/C (where Cu represents unbound concentration and C represents total concentration). |
| Unbound AUCinf (AUCinf,u) of PF-07328948 | At 0 (prior to dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post dose on Day 1 | AUCinf is the area under the plasma concentration-time profile from time zero extrapolated to infinite time. AUCinf,u is the unbound AUCinf. |
| Unbound Cmax (Cmax,u) of PF-07328948 | At 0 (prior to dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post dose on Day 1 | Cmax is the maximum plasma concentration. Cmax,u is the unbound Cmax. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | Day 1 to Day 36 |
Countries
United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed