How PF-07328948 is processed in people with and without reduced liver function

A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-COHORT STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF PF-07328948 IN ADULTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIRMENT

Adults with and without reduced liver function will take a single dose of PF-07328948 to see how their bodies process the medicine.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years to 74 Years
• Sex: All
• Sponsor: Pfizer (Industry-sponsored)
• Locations: 3 sites (Lake Forest, California and 2 other locations)
• Trial ID: NCT07269301 on ClinicalTrials.gov

What this trial studies

This Phase 1 study gives a single oral dose of PF-07328948 to groups of adults with varying levels of liver function and to healthy volunteers, and keeps participants onsite for about six days for monitoring. Blood samples will be taken at scheduled times to measure drug levels and compare pharmacokinetic parameters between groups. Participants with hepatic impairment are categorized by Child-Pugh class (A, B, or C) and must have stable disease and medications before enrollment. The goal is to determine whether decreased liver function changes how PF-07328948 is absorbed, distributed, metabolized, or eliminated.

Who should consider this trial

Good fit: Adults aged 18–75 years with BMI 17.5–40 kg/m2 and body weight ≥45 kg, including healthy volunteers and people with stable Child-Pugh A–C hepatic impairment, are the intended participants.

Not a fit: People under 18, pregnant or breastfeeding individuals, those with unstable or recently changing liver disease or medications, or those unable to remain onsite for the required monitoring are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could help clinicians choose safer or adjusted dosing for people with reduced liver function taking PF-07328948.

How similar studies have performed: Single-dose pharmacokinetic studies in people with hepatic impairment are a common and established method that have informed dosing for many other medicines.

Eligibility criteria

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.

Where this trial is running

Lake Forest, California and 2 other locations

• Orange County Research Center — Lake Forest, California, United States (Recruiting)
• Orlando Clinical Research Center — Orlando, Florida, United States (Recruiting)
• Genesis Clinical Research, LLC — Tampa, Florida, United States (Recruiting)

Study contacts

• Study coordinator: Pfizer CT.gov Call Center

Conditions Hepatic Impairment; Healthy