A Study to Investigate the Effects of Hepatic Impairment on the Pharmacokinetics of PF-07081532

• Status: Not yet recruiting
• Trial end date: 2023-09-30
• Target enrollment: 0
• Participant gender: All

Summary

The primary purpose of this study is to characterize the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (PK) of PF-07081532 following administration of a single oral dose of PF-07081532.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Pfizer

Criteria

Inclusion Criteria:

• Male or female between the ages of 18 and 70 years, inclusive 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 38.0 kg/m2, inclusive, and a total body weight >50 kg (110 lb).

• Group 1 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 1 only: no known or suspected hepatic impairment and meet the criteria based on screening laboratory liver function tests.

• Groups 2, 3 & 4 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 2, 3 & 4 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.

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or participants with suspected MTC per study doctor's judgement.

• History of acute pancreatitis within 6 months before the screening visit or any history of chronic pancreatitis.

• 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 local requirement) 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.

• For females, pregnancy, as indicated by a positive serum pregnancy test at screening and/or positive urine pregnancy test in women capable of having children at admission to study clinic

• Group 1 only: evidence of chronic liver disease including history of hepatitis, hepatitis B, or hepatitis C.

• Group 1 only: history of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of screening.

• Group 1 only: screening ECG demonstrating QTcF interval >450 ms or a QRS interval >120 ms.

• Group 1 only: screening seated systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg

• Group 1 only: use of chronic prescription medications within 7 days or 5 half-lives (whichever longer) before Day 1, or for prohibited medications, use within the required washout/restriction period.

• Group 2, 3 & 4 only: Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as <1 year in Groups 2 & 3 and <6 months for Group 4 only).

• Group 2, 3 & 4 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 2, 3 & 4 only: history of surgery that would be expected to alter absorption, distribution, metabolism, or excretion properties of PF-07081532.

• Group 2, 3 & 4 only: history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 4 weeks prior to screening.

• Group 2, 3 & 4 only: signs of clinically active Grade 3 or 4 hepatic encephalopathy

• Groups 2, 3 & 4 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 2, 3 & 4 only: previously received a kidney, liver, or heart transplant.

• Groups 2, 3, & 4 only: screening ECG demonstrating a QTcF interval >470 ms or a QRS interval >120 ms.

• Groups 2, 3 & 4 only: at screening, admission to study clinic or pre-dose on Day 1, persistent severe, uncontrolled hypertension.

• Groups 2, 3 & 4 only: ALT or AST >5x upper limit of normal on clinical laboratory tests at screening.