STUDY OF PF-06882961 IN PARTICIPANTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIREMENT

A Phase 1, Non-randomized, Open-label, Single-dose, Parallel Cohort Study to Compare the Pharmacokinetics of PF-06882961 in Adult Participants With Varying Degrees of Hepatic Impairment Relative to Participants Without Hepatic Impairment.

The current study is proposed to evaluate whether there is any clinically meaningful effect of hepatic impairment on the plasma Pharmacokinetic (PK) of PF-06882961

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hepatic Impairment
• Intervention / Treatment: Drug: PF-06882961 20MG

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Division of Clinical Pharmacology
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female participants between the ages of 18 (or the minimum country-specific age of consent if >18) and 70 years, inclusive, at the screening visit:
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body mass index (BMI) of 17.5 to 38.0 kg/m2, inclusive; and a total body weight >50 kg (110 lb), at the screening visit; with a single repeat assessment of total body weight (and hence BMI), on a separate day permitted to assess eligibility, if needed.

Exclusion Criteria:

• Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection); NOTE: Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study as long as the surgery occurred more than 6 months prior to Screening;
• At screening, participants with a positive result for human immunodeficiency virus (HIV) antibodies, as assessed by sponsor-identified central laboratory, with a single repeat permitted to assess eligibility, if needed;
• A positive COVID-19 test at screening;
• A diagnosis of type 2 diabetes mellitus (T2DM) that is documented by medical history;
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or participants with suspected MTC per the investigator's judgement;
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study;
• Use of prior/concomitant therapies
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer);
• Participants with known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF-06882961;
• Participants with ANY of the following abnormalities in clinical laboratory tests at Visit 1, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

HbA1c ≥6.5%; FPG ≥126 mg/Dl; eGFR<60 mL/min/1.73m2;

• A positive urine drug test, for illicit drugs at screening, as assessed by sponsor-identified central laboratory. However, participants in Cohorts 2-4, only, who have been medically prescribed opiates/opioids or benzodiazepines and report the use of these drugs to the investigator at the Screening visit will be allowed to participate; NOTE: repeat urine drug testing is not permitted in this study;
• At screening or Day -1, a positive breath alcohol test, as assessed using kits provided by sponsor-identified central laboratory, with a single repeat on a separate day permitted to assess eligibility, if needed;
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing and until the follow-up contact; 13. History of sensitivity to heparin or heparin-induced thrombocytopenia, only if heparin is used to flush intravenous catheters used during serial blood collections;
• Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol;
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06882961 participants without Hepatic Impairment; This arm includes participants who will receive an oral dose of PF-06882961 20 milligrams (mg) on Day 1	Drug: PF-06882961 20MG; PF-06882961 in 20 mg oral tablet will be administered on Day 1
Experimental: PF-06882961 participants with mild Hepatic Impairment; This arm includes participants who will receive an oral dose of PF-06882961 20 mg on Day 1	Drug: PF-06882961 20MG; PF-06882961 in 20 mg oral tablet will be administered on Day 1
Experimental: PF-06882961 participants with moderate Hepatic Impairment; This arm includes participants who will receive an oral dose of PF-06882961 20 mg on Day 1	Drug: PF-06882961 20MG; PF-06882961 in 20 mg oral tablet will be administered on Day 1
Experimental: PF-06882961 participants with severe Hepatic Impairment; This arm includes participants who will receive an oral dose of PF-06882961 20 mg on Day 1	Drug: PF-06882961 20MG; PF-06882961 in 20 mg oral tablet will be administered on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	Maximum observed plasma PF-06882961 concentration.	Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)	Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to infinite time.	Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)	Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to the time of the last quantifiable concentration.	Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Fraction of Unbound Drug in Plasma (fu)	fu = Cu/C (where Cu represents unbound concentration and C represents total concentration).	Predose (0 hours), and 4 hours post dose on Day 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Treatment-emergent Adverse Events (AEs)	Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. AEs included SAEs and non-serious AEs. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Relatedness to study treatment was determined by the investigator.	Baseline to Day 30
Number of Participants With Clinical Laboratory Abnormalities	Protocol-required safety laboratory assessments included: hemoglobin <0.8 x lower limit of normal (LLN), hematocrit <0.8 x LLN, erythrocytes <0.8 x LLN, ery. mean corpuscular volume >1.1 x upper limit of normal (ULN), ery. mean corpuscular hemoglobin >1.1 x ULN, platelets <0.5 x LLN, eosinophils >1.2 x ULN, activated partial thromboplastin time >1.1 x ULN, prothrombin time >1.1 x ULN, prothrombin intl. normalized ratio >1.1 x ULN; bilirubin/direct bilirubin/indirect bilirubin >1.5 x ULN, aspartate aminotransferase/alanine aminotransferase/gamma glutamyl transferase >3.0 x ULN, albumin <0.8 x LLN, urate >1.2 x ULN, bicarbonate >1.1 x ULN, triacylglycerol lipase >1.5 x ULN; urine hemoglobin/urine urobilinogen/urine nitrite/urine leukocyte esterase ≥1.	Baseline to Day 3
Number of Participants With Categorical Vital Signs Data	Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (≥) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP ≥ 20 mmHg.	Baseline to Day 3
Number of Participants With Categorical Electrocardiogram (ECG) Data	ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (≥) 300 millisecond (msec), b) ≥25% increase when baseline is > 200 msec or ≥50% increase when baseline is less than or equal to (≤) 200 msec. 2. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) ≥140 msec, b) ≥50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and ≤480 msec, b) >480 msec and ≤500 msec, c) >500 msec, d) >30 msec and ≤60 msec increase from baseline, e) >60 msec increase from baseline	Baseline to Day 3

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: C3421014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No