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.
- Registration Number
- NCT05857644
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
for healthy volunteers:
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BMI of 17.5 to 38.0 kg/m2, inclusive, and a total body weight >50 kg (110 lb).
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Capable of giving signed informed consent.
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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.
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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:
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Any condition or surgery possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection)
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Positive HIV antibodies
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Positive drug or alcohol test eGFR <60 mL/min/1.73m2 at screening
Exclusion criteria for non-healthy participants who have hepatic impairment:
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Stable concomitant meds and hepatic impairment with no change in the last 28 days
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Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as <1 year).
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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.
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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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Moderate hepatic impaired subjects PF-07923568 One time dose of 4 capsules taken orally Severe Hepatic Impaired Subjects PF-07923568 One time dose of 4 capsules taken orally. Mild Hepatic impaired subjects PF-07923568 One time dose of 4 capsules taken orally. Healthy subjects PF-07923568 One time dose of 4 capsules taken orally.
- Primary Outcome Measures
Name Time Method Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6 Cmax was the highest concentration observed directly from data
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Sisunatovir Following Administration of a Single Oral Dose Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6 AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminalphase rate constant.
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 Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6 AUClast was determined using linear/Log trapezoidal method
- Secondary Outcome Measures
Name Time Method Number of Participants With Laboratory Test Abnormalities Day -1 and Day 6 Laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute and percent total neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin and total protein), urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy, urinary albumin to creatinine ratio and urinary protein to creatinine ratio) and other tests. Abnormality was determined by the investigator. Only lab abnormalities with at least 1 occurrence in participants are reported.
Number of Participants With Vital Signs Meeting Categorical Criteria Day -1, Day 1, Day 2, and Day 6 Supine blood pressure and pulse rate were measured. Categorical classes for vital signs of potential clinical concerns were defined as followed: systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); diastolic blood pressure (DBP) \<50 mmHg; pulse rate \<40 beats per minute (bpm); pulse rate \>120 bpm, and increase from baseline in SBP ≥30 mmHg; decrease from baseline in SBP ≥30 mmHg; increase from baseline in DBP ≥20 mmHg; decrease from baseline in DBP ≥20 mmHg. The baseline measurement was the predose measurement on Day 1. Changes from baseline was defined as the change between the postdose and baseline measurements.
Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs Day -1 through follow-up (Day 29-36) Adverse event (AE) was any untoward medical occurrence in the participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious AE was any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was considered to be an important medical event. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent. AEs included both serious and non-serious AEs.
Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria Day -1, Day 1, Day 2, and Day 6 Number of participants with ECG findings meeting the following criteria: time between the onset of atrial depolarization and onset of ventricular depolarization (PR interval) ≥300 msec; time from ECG Q-wave to the end of the S wave corresponding to ventricular depolarization (QRS duration) ≥140 msec; correct time from ECG Q-wave to the end of the T wave corresponding to electrical systole for heart rate using Fridericia's formula (QTcF interval): ≥450 to \<480 msec; QTcF interval ≥480 to \<500 msec; QTcF interval: ≥500 msec; PR interval percent change from baseline (≥25/50%): ≥25% if baseline \>200 msec or ≥ 50% if baseline ≤200 msec; QRS duration percent change from baseline ≥50%; QTcF interval change from baseline: \>30 to ≤60 msec; QTcF interval change from baseline \>60 msec. The baseline measurement was the predose measurement on Day 1. Changes from baseline was defined as the change between the postdose and baseline measurements.
Trial Locations
- Locations (3)
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Genesis Clinical Research, LLC
🇺🇸Tampa, Florida, United States