A Hepatic Impairment Study for PF-04965842.

A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO COMPARE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN ADULT SUBJECTS WITH MILD AND MODERATE HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITH NORMAL HEPATIC FUNCTION

This is a Phase 1 non randomized, open label, single dose, parallel cohort study to investigate the effect of hepatic impairment on the PK, safety and tolerability of PF 04965842.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: PF-04965842

Detailed Description

A minimum of 24 subjects with normal, mild or moderate hepatic function will be enrolled into the study, with approximately 8 subjects in each cohort. The Child Pugh classification score will be utilized to assess entry criteria and to assign subjects into the appropriate hepatic impairment group. For individual subjects, the total maximum duration of study participation from the Screening visit to the end of clinical research unit (CRU) stay is approximately 31 days and approximately 63 days from the Screening visit to the Follow up contact.

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

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Clinical Research, LLC

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:

• Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 pounds).
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Additional Inclusion Criteria for subjects with hepatic impairment:

• Satisfy the criteria for Class A or Class B of the Child Pugh classification (mild: Child Pugh Scores 5 to 6 points, and moderate: Child Pugh Scores 7 to 9 points), within 14 days of investigational product administration.
• A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, computerized tomography scan, or magnetic resonance imaging (MRI).

Exclusion Criteria:

• Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days, history of disseminated herpes simplex infection or recurrent (>1 episode) or disseminated herpes zoster.
• Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

Additional exclusion criteria for subjects with hepatic impairment:

• Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as less than 1 year).
• Subjects who have previously had a transplanted kidney, liver, or heart.
• At Screening, persistent severe, uncontrolled hypertension.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-04965842; PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.	Drug: PF-04965842; PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) for PF-04965842	Cmax is maximum plasma concentration. It was observed directly from data.	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842	AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent adverse events (TEAEs) were those with initial onset or increasing in severity between the first dose of investigational product and up to 36 days post-dose.	From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law.	Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.
Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842	12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. Clinical significance of ECG recordings was determined at the investigator's discretion.	Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.
Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842	Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion.	Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21. Erratum In: Clin Pharmacokinet. 2022 Apr;61(4):591.
• Wang EQ, Le V, O'Gorman M, Tripathy S, Dowty ME, Wang L, Malhotra BK. Effects of Hepatic Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2021 Oct;61(10):1311-1323. doi: 10.1002/jcph.1858. Epub 2021 Apr 17.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Abrocitinib
• Other Study ID Numbers: B7451020

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
• product manufactured in and exported from the U.S.: Yes