A Hepatic Impairment Study for PF-04965842.
Primary Purpose
Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-04965842
Sponsored by

About this trial
This is an interventional basic science trial for Hepatic Impairment
Eligibility Criteria
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.
Sites / Locations
- Orlando Clinical Research Center
- Prism Clinical Research, LLC
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-04965842
Arm Description
PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Cmax is maximum plasma concentration. It was observed directly from data.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03626415
Brief Title
A Hepatic Impairment Study for PF-04965842.
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
April 30, 2019 (Actual)
Study Completion Date
April 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Recruitment for subjects with moderate and mild hepatic impairment (Cohorts 1 and 2) will initiate first and these subjects will be enrolled in parallel.
Masking
None (Open Label)
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-04965842
Arm Type
Experimental
Arm Description
PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.
Intervention Type
Drug
Intervention Name(s)
PF-04965842
Intervention Description
PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Description
Cmax is maximum plasma concentration. It was observed directly from data.
Time Frame
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
Title
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842
Description
AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.
Time Frame
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 Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842
Description
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.
Time Frame
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.
Title
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Description
Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law.
Time Frame
Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.
Title
Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842
Description
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.
Time Frame
Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.
Title
Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842
Description
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.
Time Frame
Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Prism Clinical Research, LLC
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Citations:
PubMed Identifier
35061234
Citation
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.
Results Reference
derived
PubMed Identifier
33749838
Citation
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.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=B7451020
Description
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