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.

Conflict of interest statement

DM, TS, MS, YK, TN and MK are employees of Astellas Pharma Inc. KO is an employee of Astellas Research Institute of America LLC. HS, KF and AU have no conflicts of interest to declare.

Figures

Fig. 1

Representative selected reaction monitoring chromatograms of blank plasma spiked with peficitinib and its metabolites (lower limit of quantification, 0.25 ng/mL). cps counts per second

Fig. 2

Participant flow. PK pharmacokinetics

Fig. 3

Mean plasma concentration–time profile of peficitinib by degree of renal impairment (linear and semi-logarithmic scale). Values are mean linear (left) and semi-logarithmic (right) scales. Classification of renal impairment was based on the predictive glomerular filtration rate equation: for males, eGFRcreat (mL/min/1.73 m2) = 194 × [serum creatinine (mg/dL)] − 1.094 × (age) − 0.287; and for females, (male eGFR) × 0.739. Definitions were: normal function ≥ 90 mL/min/1.73 m2; mild impairment ≥ 60 to < 90 mL/min/1.73 m2; moderate impairment ≥ 30 to < 60 mL/min/1.73 m2; and severe impairment ≥ 15 to < 30 mL/min/1.73 m2. eGFR estimated glomerular filtration rate

Fig. 4

The relationship between the area under the plasma concentration–time curve (AUCinf) of peficitinib and (estimated) glomerular filtration rate across the renal function groups. AUCinf area under the concentration-time curve from the time of dosing extrapolated to infinity, eGFR estimated glomerular filtration rate