Back to results

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

About this trial

This is an interventional basic science trial for Hepatic Impairment

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

NCT ID

NCT03626415

First Posted

August 8, 2018

Last Updated

April 28, 2020

Sponsor

Pfizer

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

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

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

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

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

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

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

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

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

Learn more about this trial

A Hepatic Impairment Study for PF-04965842.

We'll reach out to this number within 24 hrs