A Hepatic Impairment Study for PF-04965842.

Phase 1

Completed

• Conditions: Hepatic Impairment
• Interventions: Drug: PF-04965842

• Registration Number: NCT03626415
• Lead Sponsor: Pfizer

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.

Study Timeline

• Study First Submitted: 2018-08-08
• Study First Submitted QC: 2018-08-08
• Study First Posted: 2018-08-13
• Study Start: 2018-10-01
• Primary Completion: 2019-04-30
• Study Completion: 2019-04-30
• Status Verified: 2020-04
• Results First Submitted: 2020-04-28
• Results First Submitted QC: 2020-04-28
• Last Update Submitted: 2020-04-28
• Results First Posted: 2020-05-18
• Last Update Posted: 2020-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-04965842	PF-04965842	PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) for PF-04965842	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort	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	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort	AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842	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.	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 Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842	Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.	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 Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.	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 Vital Sign Findings of Potential Clinical Importance for PF-04965842	Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.	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.

Trial Locations

Locations (2)

Prism Clinical Research, LLC; 🇺🇸 Saint Paul, Minnesota, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States