A Renal Impairment Study for PF-04965842

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.

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.