A Study to Understand How the Study Medicine (PF-07081532) is Processed in People With Liver Dysfunction

A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL GROUP STUDY TO COMPARE THE PHARMACOKINETICS OF PF-07081532 IN ADULT PARTICIPANTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT HEPATIC IMPAIRMENT

The purpose of this study is to understand the effects of liver functional impairment on the study medicine (PF-07081532). People with liver functional impairment may process the study medicine differently from healthy people.

We are seeking participants who:

• Are between 18 and 70 years of age;
• Have a BMI (body mass index) of 17.5 to 38.0 kg/m2, inclusive, and a total body weight >50 kg (110 lbs.).

Participants will take the study medicine as a tablet once at the study clinic, and then will stay onsite for about 7 days. During this time, the study team will monitor their treatment experience and take some blood samples to test the level of PF-07081532. This will help us understand if certain level of liver functional impairment could affect the study medicine being processed in the body.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hepatic Impairment
• Intervention / Treatment: Drug: PF-07081532

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: PF-07081532 Participants without hepatic impairment; Participants without hepatic impairment will receive a single 20 mg dose of PF-07081532, administered orally as 1 PF-07081532 20 mg tablet.	Drug: PF-07081532; PF-07081532 20 milligrams (mg), 1 tablet orally, once on Day 1
Experimental: Group 2: PF-07081532 Participants with mild hepatic impairment; Participants with mild hepatic impairment will receive a single 20 mg dose of PF-07081532, administered orally as 1 PF-07081532 20 mg tablet	Drug: PF-07081532; PF-07081532 20 milligrams (mg), 1 tablet orally, once on Day 1
Experimental: Group 3: PF-07081532 Participants with moderate hepatic impairment; Participants with moderate hepatic impairment will receive a single 20 mg dose of PF-07081532, administered orally as 1 PF-07081532 20 mg tablet.	Drug: PF-07081532; PF-07081532 20 milligrams (mg), 1 tablet orally, once on Day 1
Experimental: Group 4: PF-07081532 Participants with severe hepatic impairment; Participants with severe hepatic impairment will receive a single20 mg dose of PF-07081532, administered orally as 1 PF-07081532 20 mg tablet.	Drug: PF-07081532; PF-07081532 20 milligrams (mg), 1 tablet orally, once on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of PF-07081532	Cmax is the maximum plasma concentration.	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532	AUCinf is the area under the plasma concentration-time profile from time zero extrapolated to infinite time.	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532	AUClast is the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration.	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Fraction of Unbound Drug in Plasma (Fu) of PF-07081532	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).	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Unbound Cmax (Cmax,u) of PF-07081532	Cmax,u is the unbound Cmax.	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Unbound AUCinf (AUCinf,u) of PF-07081532	AUCinf,u is the unbound AUCinf.	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1
Unbound AUClast (AUClast,u) of PF-07081532	AUClast,u is the unbound AUClast.	At 0 (prior to dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, and 144 hours post dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were defined as events that started during the effective duration of treatment (ie, starting on or after the dose of PF-07081532 up to the final follow-up visit). AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.	Day 1 to Day 36
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Safety laboratory assessments included clinical chemistry, hematology, and urinalysis tests. Number of participants with clinical laboratory abnormalities meeting pre-specified criteria is reported.	From baseline (BL) to Day 7
Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria	Vital signs abnormalities included: seated diastolic blood pressure (BP) increase and decrease from BL of >=20mmHg or absolute value <50mmHg; systolic BP increase and decrease from BL of >=30mmHg or absolute value <90mmHg; pulse rate <40 or >120bpm.	From BL to Day 7
Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria	ECG assessments included PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities included PR interval BL >200msec and max ≥25% increase from BL, or BL ≤200msec and max ≥50% increase from BL, or absolute value ≥300msec; QRS interval percent change from BL ≥50% or absolute value ≥140msec; QTcF change from BL 30- ≤60msec, >60msec, or absolute value 450- ≤480msec, 480- ≤500msec, or >500msec.	From BL to Day 7

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Healthy volunteers; Hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: C3991009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No