A Study to Learn How the Body Processes the Study Medicine PF-07328948 in People With and Without Reduced Liver Function

Pfizer

Status and phase: Enrolling; Phase 1

Conditions: Hepatic Impairment; Healthy

Treatments: Drug: PF-07328948

Study type: Interventional

Funder types: Industry

Identifiers

NCT07269301

C4921011 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 26 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 4 patient groups

Group 1: PF-07328948 participants with severe hepatic impairment

Experimental group

Description:

Participants with severe hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.

Treatment:

Drug: PF-07328948

Group 2: PF-07328948 participants with moderate hepatic impairment

Experimental group

Description:

Participants with moderate hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.

Treatment:

Drug: PF-07328948

Group 3: PF-07328948 participants with mild hepatic impairment

Experimental group

Description:

Participants with mild hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.

Treatment:

Drug: PF-07328948

Group 4: PF-07328948 participants without hepatic impairment

Experimental group

Description:

Participants without hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.

Treatment:

Drug: PF-07328948