A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers

A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN SUBJECTS WITH HEPATIC IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL HEPATIC FUNCTION

The purpose of this study is to characterize the effect of hepatic impairment on the pharmacokinetic(s) (PK) of PF-06651600 following administration of multiple once daily doses of PF-06651600. The safety and tolerability of PF-06651600 will also be evaluated in this study.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment; Healthy Participants
• Intervention / Treatment: Drug: PF-06651600 30 mg

• Study Type: Interventional
• Enrollment (Actual): 18
• 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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 40 kg/m2; and a total body weight >50 kg (110 lb)

Additional Inclusion Criteria for Participants with Normal Hepatic Function:

• Healthy male or female participants
• No known or suspected hepatic disease

Additional Inclusion Criteria for Participants with Impaired Hepatic Function:

• Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days prior to the Screening visit
• No other ongoing clinically significant abnormalities based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests except for the abnormal findings that are related to the participant's hepatic impairment.
• Satisfy the criteria for Class A or Class B of the Child-Pugh classification (mild: Child-Pugh Scores 5-6 points, and moderate: Child Pugh Scores 7-9 points), within 28 days of investigational product administration.

Exclusion Criteria:

• Has active acute or chronic infection requiring treatment or history of systemic infection requiring hospitalization, incl. herpes zoster, herpes simplex, tuberculosis
• Infection with hepatitis B, hepatitis C or HIV
• Any condition affecting drug absorption, distribution, metabolism and excretion (eg, status post porta-caval shunt surgery, prior bariatric surgery, gastrectomy, ileal resection)
• Has malignancy, lymphoproliferative disorder, surgery or other condition not allowed per protocol

Additional Exclusion Criteria for Participants with Normal Hepatic Function:

- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease

Additional Exclusion Criteria for Participants with Impaired Hepatic Function:

- Has encephalopathy, severe ascites and/or pleural effusion, Child-Pugh score >9 or medical conditions (like hepatorenal syndrome, gastrointestinal hemorrhage, etc.) excluded per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06651600 Moderate Hepatic Impairment; This arm includes participants with moderate hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.	Drug: PF-06651600 30 mg; PF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.
Experimental: PF-06651600 Healthy participants; This arm includes healthy adult participants who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.	Drug: PF-06651600 30 mg; PF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.
Experimental: PF-06651600 Mild Hepatic Impairment; This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.	Drug: PF-06651600 30 mg; PF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600	AUC24 of PF-06651600 pre and post dose.	Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Maximum Plasma Concentration (Cmax) for PF-06651600	Cmax is maximum observed plasma concentration.	Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)	AEs with all causalities were any untoward medical occurrences in a study participant administered a product which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, prothrombin time, prothrombin intl. normalized ratio), chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, sodium, potassium, calcium, bicarbonate and glucose), urinalysis (glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin and nitrite). Each parameter was evaluated against commonly used and widely accepted criteria.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Participants With Out of Range Vital Signs	Vital signs included supine blood pressure, pulse rate and temperature. The pre-specified out of range criterion for supine diastolic blood pressure was change from baseline equal to or over than (≥) 20 millimeter of mercury (mmHg). Clinical significance of vital signs and out of range criterion were determined at the investigator's discretion.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Adverse Events Leading to Discontinuation	Adverse events result in participants discontinuations from the study drug.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)

Collaborators and Investigators

• Sponsor: 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): July 19, 2019
• Primary Completion (Actual): March 5, 2020
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatic impairment; PF-06651600
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: B7981016

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