A Renal Impairment Study for PF-04965842

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: PF-04965842


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1 will be conducted. The 8 subjects from the renal impaired group will be recruited before recruiting the 8 subjects without renal impairment function in Part 1. After statistical evaluation of results from Part 1, Part 2 may be conducted.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04965842<br>PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor | Drug: PF-04965842<br>* PF 04965842 is a janus kinase (JAK) 1 inhibitor that is currently being developed for the treatment of atopic dermatitis (AD).<br>|

What is the study measuring?
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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 |