A Renal Impairment Study for PF-04965842

A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN SUBJECTS WITH RENAL IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL RENAL FUNCTION

This study is a phase 1 non-randomized, open-label, single-dose, parallel-group study of PF 04965842 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with moderate renal impairment (Part 2).

Study Overview

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

Detailed Description

This is a Phase 1 non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-04965842 after a single 200 mg oral dose. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted and approximately 8 subjects with moderate renal impairment will be enrolled. The total duration of participation from the Screening Visit to Day 4 will be a maximum of 31 days and from the Screening Visit to Follow-up Contact/Visit will be a maximum of 67 days.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Be-bru
    • Brussels, Be-bru, Belgium, B-1070
      • Brussels Clinical Research Unit
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33136
      • University of Miami Division of Clinical Pharmacology
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Breath alcohol test at Screening and Day -1 must be negative.
• Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m2; and a total body weight >50 kg (110 lb).

Additional inclusion criteria for subjects with renal impairment:

• Meet the following eGFR criteria during the screening period based on the MDRD equation:

  • Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.
  • Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and <60 mL/min.
• Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
• Stable concomitant drug regimen.

Exclusion Criteria:

• Renal transplant recipients.
• Urinary incontinence without catheterization.
• 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 prior to baseline, history of disseminated herpes simplex infection or recurrent 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.
• History of or current positive results for human immunodeficiency virus, Hepatitis B, Hepatitis C.

Additional exclusion criteria for subjects with renal impairment:

• Subjects requiring hemodialysis and peritoneal dialysis.
• Screening BP ≥ 180 mm Hg (systolic) or ≥ 110 mm Hg (diastolic).
• Screening supine 12-lead ECG demonstrating QTcF >470 msec or a QRS interval >120 msec.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• 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 oral selevtive janus kinase (JAK) 1 inhibitor	Drug: PF-04965842; PF 04965842 is a janus kinase (JAK) 1 inhibitor that is currently being developed for the treatment of atopic dermatitis (AD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) for PF-04965842	Maximum observed plasma PF-04965842 concentration.	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842	Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)	Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)	Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)	Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)	Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).	0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator.	Baseline up to Follow-Up (Day 36)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria.	Baseline, post-dose on Day 1, Day 2 and Day 4.
Number of Participants With Clinically Significant Vital Sign Values	Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.	Day 1 (pre-dose) and Day 4
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values	Clinical significance of ECG data was assessed by the investigator.	Baseline, post-dose on Day 1 and on Day 4

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Wang EQ, Le V, Winton JA, Tripathy S, Raje S, Wang L, Dowty ME, Malhotra BK. Effects of Renal Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2022 Apr;62(4):505-519. doi: 10.1002/jcph.1980. Epub 2022 Feb 15.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Actual): November 5, 2019
• Study Completion (Actual): November 5, 2019

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 4, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Abrocitinib
• Other Study ID Numbers: B7451021; 2018-002865-20 (EudraCT Number)

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