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

• ClinicalTrials.gov Identifier: NCT05478603
• Recruitment Status: Completed
• First Posted: July 28, 2022
• Last Update Posted: May 3, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hepatic Impairment; Healthy Volunteers	Drug: PF-07081532	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: August 1, 2022
• Actual Primary Completion Date: April 5, 2023
• Actual Study Completion Date: April 5, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Maximum plasma concentration (Cmax) [ Time Frame: up to day 7 ]
2. Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf) [ Time Frame: up to day 7 ]
3. Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) [ Time Frame: up to day 7 ]
   AUClast and AUClast,u will be treated as primary endpoints if data do not permit robust estimation of AUCinf and AUCinf,u, otherwise they will be treated as tertiary endpoints
4. Fraction of unbound drug in plasma (fu) [ Time Frame: Day 1 ]
5. Unbound maximum plasma concentration (Cmax, u) [ Time Frame: up to day 7 ]
6. Unbound area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf,u) [ Time Frame: up to day 7 ]
7. Unbound area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast,u) [ Time Frame: up to day 7 ]
   AUClast and AUClast,u will be treated as primary endpoints if data do not permit robust estimation of AUCinf and AUCinf,u, otherwise they will be treated as tertiary endpoints

Secondary Outcome Measures :

1. Number of participants with treatment emergent adverse events (AEs) [ Time Frame: Baseline to Day 29 ]
2. Number of participants with treatment emergent clinically significant clinical laboratory abnormalities [ Time Frame: Baseline to Day 7 ]
3. Number of participants with treatment emergent clinically significant change from baseline in vital signs [ Time Frame: Baseline to Day 7 ]
4. Number of participants with treatment emergent clinically significant abnormal electrocardiograms (ECG) [ Time Frame: Baseline to Day 7 ]

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Florida

Orlando Clinical Research Center

Orlando, Florida, United States, 32809

Genesis Clinical Research, LLC

Tampa, Florida, United States, 33603

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05478603
• Other Study ID Numbers: C3991009
• First Posted: July 28, 2022
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

Hepatic impairment; Healthy volunteers

Additional relevant MeSH terms:

Liver Diseases; Digestive System Diseases