PMID- 27162173
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20180129
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 5
IP  - 6
DP  - 2016 Nov
TI  - Pharmacokinetics, Pharmacodynamics, and Safety of ASP015K (Peficitinib), a New 
      Janus Kinase Inhibitor, in Healthy Subjects.
PG  - 435-449
LID - 10.1002/cpdd.273 [doi]
AB  - 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 (AUC(inf) ) 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.
CI  - (c) 2016, The American College of Clinical Pharmacology.
FAU - Cao, Ying Jun
AU  - Cao YJ
AD  - Astellas Pharma Global Development, Northbrook, IL, USA.
FAU - Sawamoto, Taiji
AU  - Sawamoto T
AD  - Astellas Pharma, Inc, Tokyo, Japan.
FAU - Valluri, Udaya
AU  - Valluri U
AD  - Astellas Pharma Global Development, Northbrook, IL, USA.
FAU - Cho, Kathy
AU  - Cho K
AD  - Astellas Research Institute of America, LLC, Skokie, IL, USA.
FAU - Lewand, Michaelene
AU  - Lewand M
AD  - Formerly Astellas Pharma Global Development, Northbrook, IL, USA; currently 
      Pharma Start, LLC, Northbrook, IL, USA.
FAU - Swan, Suzanne
AU  - Swan S
AD  - Formerly Davita Clinical Research, Minneapolis, MN, USA; currently Minneapolis VA 
      Health Care System, Minneapolis, MN, USA.
FAU - Lasseter, Kenneth
AU  - Lasseter K
AD  - Clinical Pharmacology of Miami, Miami, FL, USA.
FAU - Matson, Mark
AU  - Matson M
AD  - Prism Clinical Research, St. Paul, MN, USA.
FAU - Holman, John Jr
AU  - Holman J Jr
AD  - Astellas Pharma Global Development, Northbrook, IL, USA.
FAU - Keirns, James
AU  - Keirns J
AD  - Astellas Pharma Global Development, Northbrook, IL, USA.
FAU - Zhu, Tong
AU  - Zhu T
AD  - Astellas Pharma Global Development, Northbrook, IL, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160630
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Janus Kinase Inhibitors)
RN  - 25X51I8RD4 (Niacinamide)
RN  - HPH1166CKX (peficitinib)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/adverse effects/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Food-Drug Interactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Janus Kinase Inhibitors/adverse effects/*pharmacokinetics/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - Niacinamide/adverse effects/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Young Adult
OTO - NOTNLM
OT  - ASP015K
OT  - peficitinib
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - safety
OT  - tolerability
EDAT- 2016/05/11 06:00
MHDA- 2018/01/30 06:00
CRDT- 2016/05/11 06:00
PHST- 2015/10/22 00:00 [received]
PHST- 2016/04/25 00:00 [revised]
PHST- 2016/05/05 00:00 [accepted]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
PHST- 2016/05/11 06:00 [entrez]
AID - 10.1002/cpdd.273 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2016 Nov;5(6):435-449. doi: 10.1002/cpdd.273. Epub 2016 
      Jun 30.