Clinical trial NCT05478603: A Study to Understand How the Study Medicine (PF-07081532) is Processed in People With Liver Dysfunction
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy Volunteers
Keywords: Hepatic impairment
Healthy volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-07-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of PF-07081532
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532
timeFrame: 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
measure: Fraction of Unbound Drug in Plasma (Fu) of PF-07081532
timeFrame: 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
measure: Unbound Cmax (Cmax,u) of PF-07081532
timeFrame: 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
measure: Unbound AUCinf (AUCinf,u) of PF-07081532
timeFrame: 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
measure: Unbound AUClast (AUClast,u) of PF-07081532
timeFrame: 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 outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to Day 36
measure: Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: From baseline (BL) to Day 7
measure: Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
timeFrame: From BL to Day 7
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
timeFrame: From BL to Day 7
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research, LLC
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: