Clinical trial NCT05857644: A Study to Compare How the Study Medicine (PF-07923568) is Processed in Participants With Different Levels of Loss of Liver Function to Healthy Participants.
Official title: A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL GROUP STUDY TO COMPARE THE PHARMACOKINETICS OF PF-07923568 IN ADULT PARTICIPANTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT HEPATIC IMPAIRMENT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liver Diseases
Hepatic Impairment
Keywords: healthy volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-05-12
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open-label, single dose, parallel group, multicenter study to investigate the effect of varying degrees of hepatic function on the plasma PK of PF-07923568 after a single, oral 200 mg dose administered in the fed state (standard breakfast).
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to learn how the study medicine (PF-07923568) is processed in participants with liver function loss compared to healthy participants. The different levels of liver function loss can be mild, moderate or severe.

This study is seeking participants who:

* are male or female of 18 years of age or older.
* are examined to be healthy (group with no loss of liver function).
* have mild, moderate, and severe liver disease (group with loss of liver function).

All participants will receive a one-time dose of 4 capsules of PF-07923568 which will be taken by mouth. All participants will remain at the study clinic for 6 days for safety review and laboratory collections. This is to see how the study medicine is being broken down by the liver over time.

All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are examined to see whether they are fit for the study. During this period, the participant's medical history and past and current medications will be reviewed. A series of tests will also be performed to see if they are good to be selected for the study. If the participant meets all required criteria and are interested in continuing, the participant will be brought into the study clinic to stay overnight for 6 days. On day 6, the participant will be discharged. About 28 to 35 days after discharge, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to conclude the study.


Eligibility criteria: Inclusion Criteria: for healthy volunteers:

* BMI of 17.5 to 38.0 kg/m2, inclusive, and a total body weight \>50 kg (110 lb).
* Capable of giving signed informed consent.
* At screening, no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, including BP and pulse rate measurement, standard 12-lead ECG and clinical laboratory tests.
* body weight within +/-15 kg of the average of pooled hepatic impaired group and +/- 10 years of the average pooled hepatic impairment group.

  --Exclusion criteria for all participants:
* Any condition or surgery possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection)
* Positive HIV antibodies
* Positive drug or alcohol test eGFR \<60 mL/min/1.73m2 at screening

Exclusion criteria for non-healthy participants who have hepatic impairment:

* Stable concomitant meds and hepatic impairment with no change in the last 28 days
* Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as \<1 year).
* A diagnosis of hepatic dysfunction secondary to any acute ongoing hepatocellular process that is documented by medical history, PE, liver biopsy, hepatic ultrasound, CT scan, or MRI.
* History of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 4 weeks prior to screening.

  --Severe ascites and/or pleural effusion, except for those categorized as severe hepatic impairment who may be enrolled provided participant is medically stable, per the investigators' medical judgment.
* Previously received a kidney, liver, or heart transplant. ALT/AST greater than 5X upper limit normal

Primary outcomes:
measure: Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose
timeFrame: Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6
measure: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Sisunatovir Following Administration of a Single Oral Dose
timeFrame: Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6
measure: Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose
timeFrame: Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6
Secondary outcomes:
measure: Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs
timeFrame: Day -1 through follow-up (Day 29-36)
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Day -1 and Day 6
measure: Number of Participants With Vital Signs Meeting Categorical Criteria
timeFrame: Day -1, Day 1, Day 2, and Day 6
measure: Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria
timeFrame: Day -1, Day 1, Day 2, and Day 6
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
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: