Clinical trial NCT03626415: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-08-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for PF-04965842
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842
timeFrame: 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.
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.
measure: Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842
timeFrame: Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.
measure: Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842
timeFrame: Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Saint Paul
country: United States
facility: Prism Clinical Research, LLC
state: Minnesota
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.
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.