title: Pharmacokinetics, Pharmacodynamics, and Safety of ASP015K (Peficitinib), a New Janus Kinase Inhibitor, in Healthy Subjects.
abstract: Two randomized, double-blind, placebo-controlled studies are reported that had the objective to evaluate the pharmacokinetics, pharmacodynamics, and safety of ASP015K (peficitinib), a Janus kinase (JAK) inhibitor, in healthy subjects. The single-dose study included 7 male groups (3-300 mg) and 2 female groups (30 or 200 mg), n = 8/group (6 on ASP015K and 2 on placebo in each group). The multiple-dose study included 1 female and 3 male groups, n = 12/group (9 on ASP015K and 3 on placebo in each group), who received ASP015K (30 mg) or placebo every 12 hours (twice a day) for 14 days. In the single-dose study, plasma ASP015K concentration increased dose-proportionally. Food increased ASP015K exposure (AUCinf) by 27%. Mean peak JAK inhibition increased with dose, from 6% at 4 hours (median) following ASP015K 3 mg to 93% (range, 89%-98%) at 2 hours (median) after ASP015K 300 mg. In the multiple-dose study, ASP015K plasma exposure reached steady state by day 3. On day 14, mean ASP015K peak concentration was 38%-65% higher than after the first dose; peak JAK inhibition following 100 or 200 mg twice daily was >85%. The most common adverse events (AEs) were neutropenia, headache, and abdominal pain; no serious AEs occurred. The safety findings at pharmacologically effective doses of ASP015K support further clinical development.
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: Ying Jun
authors.initials: YJ
authors.lastname: Cao
authors.affiliation: Astellas Pharma, Inc, Tokyo, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Sawamoto
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: Udaya
authors.initials: U
authors.lastname: Valluri
authors.affiliation: Astellas Research Institute of America, LLC, Skokie, IL, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Cho
authors.affiliation: Formerly Astellas Pharma Global Development, Northbrook, IL, USA; currently Pharma Start, LLC, Northbrook, IL, USA.
authors.forename: Michaelene
authors.initials: M
authors.lastname: Lewand
authors.affiliation: Formerly Davita Clinical Research, Minneapolis, MN, USA; currently Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Swan
authors.affiliation: Clinical Pharmacology of Miami, Miami, FL, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lasseter
authors.affiliation: Prism Clinical Research, St. Paul, MN, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Matson
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: John
authors.initials: J
authors.lastname: Holman
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: Keirns
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000075242:Janus Kinase Inhibitors; D009536:Niacinamide; C000608065:peficitinib; D000218:Adamantane
keywords: ASP015K; peficitinib; pharmacodynamics; pharmacokinetics; safety; tolerability