Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects with Normal and Impaired Renal Function

Abstract

Background and Objective This study measured and compared the exposure and safety of peficitinib (ASP015K), a novel oral Janus kinase inhibitor, in subjects with normal and impaired renal function after a single oral, clinically relevant peficitinib dose. Methods This was an open-label, parallel-group study conducted at two centres in Japan. Subjects with normal and mildly, moderately, or severely impaired renal function received a single oral dose of peficitinib (one 150 mg tablet) under fasting conditions in a hospital setting. Blood samples were collected prior to administration and up to 72 h post-dose for pharmacokinetic assessment. Safety was assessed up to 7 days post-dose. Results Peficitinib plasma concentration-time profiles were similar between those with normal and impaired renal function. In subjects with impaired renal function, area under the plasma concentration-time curve and maximum concentration were 0.8-to 1.1-fold those in subjects with no impairment. Two subjects (one in the normal group and one in the mildly impaired group) each experienced a treatment-emergent adverse event (TEAE). There were no serious TEAEs, deaths or TEAEs leading to treatment withdrawal. Conclusions Peficitinib exposure and TEAEs were similar in subjects with and without renal impairment after a single oral 150 mg dose. Based on these findings, it is not expected that peficitinib dose adjustment will be required in clinical practice, according to the degree of renal impairment. ClinicalTrials.gov identifier NCT02603497.

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“…Following a single dose of peficitinib 150 mg, the AUC inf geometric mean ratios (GMR) in subjects with mild, moderate, and severe renal impairment versus subjects with normal renal function were 0.87 (90% confidence interval [CI] 0.61-1.25), 0.83 (90% CI 0.58-1. 19), and 1.09 (90% CI 0.74-1.60), respectively [61]. Thus, peficitinib plasma concentration does not appear to be significantly affected by impaired renal function.…”

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