Phase 1 N=24 Basic Science

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

Hepatic Impairment · Healthy Volunteers

Bottom Line

View on ClinicalTrials.gov: NCT05478603 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Aug 2024

Primary outcome: Primary: Maximum Plasma Concentration (Cmax) of PF-07081532 — 2236; 2121; 2230; 1536 nanogram per milliliter (ng/mL)

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: PF-07081532 (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Pfizer
Primary completion: Apr 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Maximum Plasma Concentration (Cmax) of PF-07081532	2236; 2121; 2230; 1536	—
PRIMARY Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07081532	43200; 44010; 67430; 41680	—
PRIMARY Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07081532	40990; 41900; 62680; 39800	—
PRIMARY Fraction of Unbound Drug in Plasma (Fu) of PF-07081532	0.0002753; 0.0002568; 0.0002937; 0.0006780	—
PRIMARY Unbound Cmax (Cmax,u) of PF-07081532	0.6156; 0.5448; 0.6551; 1.042	—
PRIMARY Unbound AUCinf (AUCinf,u) of PF-07081532	11.88; 11.30; 19.81; 28.24	—
PRIMARY Unbound AUClast (AUClast,u) of PF-07081532	11.29; 10.76; 18.41; 27.02	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs)	1; 0; 0; 1; 0; 0	—
SECONDARY Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0; 0; 0; 3; 0; 0	—
SECONDARY Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria	0; 0; 1; 0; 1; 0	—
SECONDARY Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria	0; 0; 0; 0; 0; 0	—

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 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 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05478603). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.